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Rejuvenation Research Is Now a Mainstream Topic – Article by Steve Hill

Rejuvenation Research Is Now a Mainstream Topic – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, originally published on August 26, 2019, by the Life Extension Advocacy Foundation (LEAF), Mr. Steve Hill reviews an MIT Technology Review article authored by David Adam. Mr. Adam gives his view of the research field of aging, and Mr. Hill is impressed by the factualism compared to the MIT Technology Review’s previous articles that covered the topic. Mr. Hill goes on to discuss aging and lifespan in other species and address the question: Is aging a disease, and does it really matter?

~Bobby Ridge, Assistant Editor, September 9, 2019


It is a sure sign that the tide has turned when mainstream news outlets and magazines start publishing positive articles about aging research and the prospects of rejuvenation.

A refreshing change

Today, I want to highlight an article in MIT Technology Review in which the author, David Adam, gives a sensible and measured overview of what is happening in the field and manages to sidestep the usual negativity and misconceptions that often plague popular science pieces.

Since ancient times, aging has been viewed as simply inevitable, unstoppable, nature’s way. “Natural causes” have long been blamed for deaths among the old, even if they died of a recognized pathological condition. The medical writer Galen argued back in the second century AD that aging is a natural process.

His view, the acceptance that one can die simply of old age, has dominated ever since. We think of aging as the accumulation of all the other conditions that get more common as we get older—cancer, dementia, physical frailty. All that tells us, though, is that we’re going to sicken and die; it doesn’t give us a way to change it. We don’t have much more control over our destiny than a Cyclops.

But a growing number of scientists are questioning our basic conception of aging. What if you could challenge your death—or even prevent it altogether? What if the panoply of diseases that strike us in old age are symptoms, not causes? What would change if we classified aging itself as the disease?

The article skips the sensationalism and assumptions that many journalists typically make about aging research; instead, we get a solid piece of factual journalism. This is in stark contrast to the reporting done by this outlet a few years ago, as it had published irrationally skeptical and frequently negative coverage of the field and the science behind it.

This may be partially due to changes to the editorial staff at the magazine, which happened in 2017, but it is also indicative of the wider acceptance of the idea that we may be able to do something about aging. The same magazine has even published a special issue entitled Old Age is Over! – If you want it, which takes a deeper dive into the topic, though this is paid content.

There may be a choice about how we age

For millennia, it has been assumed that aging is a one-way street and that we must simply accept that there is nothing we can do about it, aside from facing age-related ill health with stoicism. However, the situation has somewhat changed. As researchers have discovered more about how aging works, the processes driving it, and the results from model animals, it has become increasingly clear to many people that something might be done about aging in order to delay, prevent, or potentially reverse age-related diseases.

We already know that a number of species do not age; this phenomenon is known as negligible senescence. This simply means that the organism does not show a decline of survival characteristics, such as muscle strength, mobility, and senses. Such species also do not experience an increased mortality rate with advancing age or a loss of reproductive capability with age.

These species tend to have much more efficient repair systems that are capable of offsetting and repairing damage rapidly enough to prevent it from accumulating and snowballing out of control as it does in humans. We are relatively long-lived as a species, but, compared to some longevity champions, such as the bowhead whale at 200 years plus, the Greenland shark at 400 or more years, and the ocean quahog clam, which lives at least 507 years, our lifespan is relatively brief.

So, the race is now on to see if we can develop therapies to repair age-related damage, slow down how fast that damage accrues, and see if we can emulate these kings of longevity. The key take-home message here is that there is no biological reason that humans might not live longer, healthier lives if such therapies are developed.

Exactly how long that might be is a matter of speculation; it could be a few years, a decade or two, or perhaps more. The key point is that the researchers who are developing these therapies are aiming to make those extra years healthy ones, and that is surely something that most people can get behind.

Is aging a disease, and does it really matter?

Some researchers propose that aging is a disease, and while this is a somewhat contentious view, it has some merit and is absolutely worthy of further discussion. We discussed if aging is natural or pathological in a previous article, and while the case can certainly be made that aging is a disease, it may more accurately fit the description of a co-morbid syndrome: a group of symptoms that consistently occur together and a condition characterized by a set of associated symptoms.

Whether or not they believe in either the disease hypothesis or maximum life spans, most experts agree that something has to change in the way we deal with aging. “If we don’t do something about the dramatic increase in older people, and find ways to keep them healthy and functional, then we have a major quality-­of-life issue and a major economic issue on our hands.” – Dr. Brian Kennedy

This matter is largely a matter of semantics, and the important thing is that, from a regulatory point of view, including aging as a disease state or syndrome would make it easier to develop therapies that directly target the aging processes themselves. Currently, therapies must focus on single diseases in order to progress through clinical trials, which is not the most optimal approach.

However, it is my personal view that this situation will not change much until the first successful human demonstration of rejuvenation therapy occurs. Until then, researchers will continue to work within the current regulatory system, and while this is, by its nature, slower, it does not prevent progress being made. Fortunately, there are now a lot of companies working in this space, and a number of therapies are quite far along in development.

A therapy that works in humans against one age-related disease by targeting an aging process directly could potentially treat a slew of other related diseases, and so any successful therapy making it through the system would likely rapidly see off-label usage for other, similar conditions.

Conclusion

In closing, it is refreshing to see more balanced and fair reporting on the field and the science of aging rather than the negative and highly biased material that this outlet had published prior to 2017. Reasonable skepticism is perfectly understandable, especially in a field as cutting-edge as rejuvenation biotechnology, which is charting unknown waters and attempting to do what has long been thought impossible.

However, the weight of evidence, the results of a myriad of animal studies demonstrating age reversal, and the rapid increase of scientific understanding should balance that skepticism in anyone interested in science and the actual facts. A magazine devoted to science really should be at the top of its game when reporting the facts, and this and other recent articles on the topic have been much closer to this mark. Oh my, how times have changed.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity, created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

An Open Letter to the Transhumanist Community – Article by Arin Vahanian

An Open Letter to the Transhumanist Community – Article by Arin Vahanian

Arin Vahanian


During the events that have transpired over the past few weeks, many of which have affected (and not in positive ways, sometimes) the USTP, Humanity+, and other organizations in the Transhumanism movement, I have mostly refrained from sharing my opinions and thoughts. However, I feel it is time now to share something that has been on my mind for a while.

But before I do so, I would like to express my disappointment at the level of discourse I am seeing in our community as a whole. Just a few days ago, the USTP released a statement condemning the vicious, vindictive manner in which someone in the Transhumanist community treated other members, as well as USTP Officers.

Instead of using this as a rallying cry for greater cooperation, an opportunity for increased self-awareness, as well as coordination on our shared goals, we now, yet again, have a candidate attacking another candidate, insulting their intelligence, not to mention their physical appearance.

Such petty, cruel behavior not only reflects negatively upon the person engaging in such behavior, but also reflects negatively on Transhumanism as a whole.

The sad truth of the matter, and what has been on my mind for a long while, but which I have been reluctant to share, is that many of the things that members of the general public dislike about Transhumanism, we have displayed here with great fervor, whether intentionally, or not.

Indeed, in some ways, we ourselves have become our worst enemies, treating each other with disdain, pretending that we are somehow more intelligent than others, disregarding the legitimate objections people have brought forward about the consequences of technology, ignoring how bizarre or unhinged some of our behaviors and actions may appear to the public, and being generally disconnected from the needs of the population as a whole.

However, it is not only a single candidate or person who is responsible for helping to create an environment in which arrogance, narcissism, unstable behavior, a lack of civility, pettiness, and a lack of empathy have persisted.

Sadly, we in the Transhumanist community are all responsible, because we have all allowed this sort of behavior to continue, over many months and many years. To be sure, this sort of behavior has been around long before this current USTP Presidential campaign started, but it continues, nonetheless.

One thing I have been passionate about and dedicated to from day one is to change the public’s perception of Transhumanism. To grow a movement that is small, into a worldwide force that is capable of great positive change, requires us to have a finger on the pulse of the views of the general public.

Vitriol is still vitriol, and venom is still venom, whether we sling it with bows and arrows, or whether we drop it like a bomb. We have no business complaining about the lack of civility in politics, in any country, when we ourselves are guilty of incivility. We should not lament the proliferation of cyberbullying when we ourselves engage in the same behavior.

We could say, once again, that the way we conduct ourselves in front of the general public influences greatly their opinions about Transhumanism, but this message has been nearly as ineffective as advocating for peace in the Middle East. We could say, once again, that we are a team, and that the shared goals we have are far more important than our disagreements with each other, but that doesn’t seem to have helped very much. We could say, once again, that humanity could benefit greatly from increased longevity, improved health, and the complete eradication of poverty, but even this, surprisingly, doesn’t seem to register with some people.

So let me put it this way, instead – the next time you think about hurling abuse at someone in our community, the next time you feel like getting even with someone for their past transgressions, consider the fact that in just a few decades, unless we achieve our objectives with anti-aging research and life extension, everyone here will likely be dead.

Dead, as in, they will no longer be able to hold a loved one in their arms. Dead, as in, they’ll never again feel the warm rays of the sun caressing their face on a summer morning. Dead, as in, they’ll never have the pleasure of tasting their favorite food again, or any food, for that matter.

In many ways, the movement has never been stronger. Transhumanism has been garnering more press coverage, thanks to the efforts of people like Zoltan Istvan. USTP membership has grown substantially in recent weeks and months, thanks to the leadership of Gennady Stolyarov. The work that pioneers such as Fereidoun Esfandiary (also known as FM-2030), Aubrey de Grey, Nick Bostrom, and Jose Cordeiro have done over decades has helped built the foundation for what we are able to do now.

Every time we attack each other, we dishonor the legacy the hard-working people in our movement have created. Every time we attack each other, it sets us back from important work we could be doing to help humanity with its greatest challenges.

Contrary to what some people may think, the work that Transhumanists are doing does not only benefit the Transhumanist community; it benefits people who don’t even know about us. It benefits people who are suffering from a rare disease and feel there is no light at the end of the tunnel. It benefits people who are struggling with crippling poverty, having to make a choice between starving to death or being homeless.

The indignation we may feel, righteous or not, at the lack of awareness and acceptance of our movement among the general public, isn’t the general public’s fault. It is simply because we have been unable, thus far, to clearly demonstrate, with a compassionate and unified voice, the many worthy and noble projects we are engaged in, as well as our vision, mission, and purpose. But there is no rule that says that this state of affairs has to continue.

Being able to demonstrate to the world the optimistic, humanitarian, and thoughtful goals of Transhumanism requires us to take a good look in the mirror and decide who we are, and who we want to be. But most importantly, it requires us to be optimistic, humanitarian, and thoughtful, ourselves. How we treat others is an indication, on some level, of how we look at the world as a whole.

Requesting that people be treated with respect, dignity, and kindness is not authoritarianism or fascism. It is called being a better human being. And one of the core tenets of Transhumanism is being a better human being. So let us start today, right now, by being better, not just to ourselves, but also to each other.

Arin Vahanian is Director of Marketing for the U.S. Transhumanist Party / Transhuman Party. 

An Interview with Sergey Young by Nicola Bagalà

An Interview with Sergey Young by Nicola Bagalà

Sergey Young
Nicola Bagalà


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Nicola Bagalà, originally published by the Life Extension Advocacy Foundation (LEAF) on July 4, 2019. In this article, Mr. Bagalà interviews Sergey Young, a board member of XPRIZE and the creator of the $100 million Longevity Vision Fund. They cover a number of topics, such as the longevity companies that Sergey has invested in, the Longevity Xprize, Sergey’s new book, callled Growing Young: A Simple Guide to Age Reversal, along with many more topics. I highly recommend this read.

~ Bobby Ridge, Assistant Editor, July 8, 2019


We recently had the opportunity to interview Sergey Young, a board member of XPRIZE and the creator of the $100 million Longevity Vision Fund.

When did you first become interested in healthy life extension, and why?

My interest began with a routine visit to a doctor. Five years ago, at the age of 42, my blood tests – which I neglected for 7 years, thinking I was in perfect health – showed that my cholesterol was extremely high, putting me at risk of one of the most common killers: heart disease.

The only treatment offered by my doctor at the time was to take statins (cholesterol-reducing medication) for the rest of my life. However, this seemed unnatural and potentially dangerous for the body, and I definitely did not want to “live” on a pill forever. I refused to accept this as the only option (the doctor even made me sign a waiver for refusing treatment) and kept pushing for alternatives. Eventually, the doctor suggested I try a Mediterranean-style diet (based around healthy fats, cutting out sugar, etc.), which worked in bringing my cholesterol down to a normal range without any medication at all.

It’s a pity that doctors, even well-meaning ones, do not start with dietary changes first. Since then, I developed an interest in diet and a lifestyle-based approach to health and longevity, and hope I can share this knowledge with as many people as possible.

However, it was the meeting with Peter Diamandis last year in Vatican City at a conference on regenerative medicine, which was also attended by the Pope, that really kickstarted my mission in longevity. Peter is such an inspiring individual, and his XPRIZE Foundation served as a great example of how you can make a difference on a large scale. It was the perfect platform to make my interest in longevity serve to the benefit of society as a whole.

In your opinion, what are the most important reasons why the pursuit of healthy longevity should be a priority for human society?

Our lives are like “Groundhog Day”: we spend most of our lives working until we decline into old age and illness – possibly without having had the time or health to enjoy life to the fullest.

However, pursuing healthy longevity can potentially extend our lives by 25% or more. Having an extra 25 years of lifespan gives us the opportunity to pursue our dreams, spend more time with our children and grandchildren, and do the things that really matter – but that we have not had time for.

This cause is so close to your heart that you’re actually writing a book about it—no easy task. Is it your first book?

Yes, this is my first book. Hopefully not my last.

I am putting a lot of time and effort into making longevity as practical and easy to read about as possible. I see it as a way of helping as many people as possible learn about life extension and making their lives more longevity-friendly. If this leads to follow-on books, covering longevity diets, or longevity exercises, for example, I would be happy to fulfill the readers’ requests.

What made you decide that it was time for you to write one?

When I first got into longevity, there were only two types the longevity books available: either 300-page books with a single hypothesis drawn out, or “encyclopedias” that were nearly impossible for the general population to read without a specialized degree.

That’s why I decided to write “Growing Young: Simple Guide to Age Reversal” – something well-researched and comprehensive, yet simple and engaging for the general reader.

I understand that we’re some way from finding your book on the shelves; can you give us a sneak peek by telling us a little about what topics you’re going to cover?

The book is heavy-packed with a lot of varied content. Here is a taster of some of the topics included:

  • Technological longevity breakthroughs – what is already available that can extend our lifespans by up to 10 years, and technologies that could emerge in the near future to extend our lifespans even further
  • Ethical trade offs of living to 200
  • Economics of longevity

Has a release date, or time frame, for the book been decided yet?

Our planned release date is spring 2020.

You’re the founder of the Longevity Vision Fund, whose goal is to accelerate longevity breakthroughs and make them affordable for as many as possible as soon as possible. Many people fear that life extension would be only for the rich, so what’s your plan to make your vision come true, especially regarding affordability?

The focus of Longevity Vision Fund is on affordable and accessible technology. As with every area of technology, it undergoes a democratization process, becoming progressively more affordable to a wider range of people. The mission of Longevity Vision Fund is to enable and speed up the democratization of longevity-related technology by investing in companies and services that have the potential to become scalable, accessible, and affordable for the general population.

LVF is a rather new initiative; what has it achieved thus far?

Longevity Vision Fund was launched in February 2019, but we have already come a long way. For example, we raised most of the capital in just 3 months. We have assembled an impressive Advisory Board of five leading longevity scientists: Aubrey De Grey, Vadim Gladyshev, Joao de Magalhaes, Richard Faragher, and Morten Scheibye-Knudsen.

We also entered into a collaboration partnership with BOLD Capital (Peter Diamandis’s fund), and LVF has already invested in four companies to date.

What areas of life extension research, or life extension in general, will be LVF’s primary focus?

We like to invest in fields such as AI, diagnostics, wearables & devices, stem-cell treatments, and organ regeneration.

Does LVF have a roadmap, or a tentative time frame, describing when specific goals should ideally be achieved?

As mentioned above, we have already achieved very significant milestones for a fund that has just been launched last year. Our main goal for the future is achieving our mission in stimulating progress in longevity breakthroughs to make them affordable to as many people as possible.

This is a progressive goal, and it would be impossible and irresponsible to make specific claims exactly as to when and by how much lifespans will be expanded.

Let’s talk about XPRIZE a little bit. You’ve been on the XPRIZE Innovation Board for over a year now. What is your job as a member of this board?

In addition to being on the XPRIZE Innovation Board, I am also the Development Sponsor of Longevity XPRIZE. My job is to define the strategy of Longevity XPRIZE, help choose the areas of most impact, and attract and unite the brightest minds that could lead solutions to the world’s biggest problems – aging being one of them, since it affects us all.

What led you to join XPRIZE?

As you probably already know, I am extremely passionate about longevity, and I want to use it to make a difference in the world. I want to help people live longer, healthier, and happier lives. Since meeting Peter Diamandis, XPRIZE has become the perfect high-impact platform for working on the world’s biggest issues

Speaking of XPRIZE, you took part in its recent Future of Longevity brainstorming session, in which our president, Keith Comito, had the pleasure to meet you. Can you share your impressions of the event?

As the Development Sponsor, I could be biased, so I would be more interested in hearing Keith Comito’s thoughts!

On a serious note, I thought it turned out to be a great, collaborative event with a constellation of over 50 of the world’s Longevity Leaders. I am grateful to everyone who came and made it such a success.

The goal of the brainstorming session was to design a Longevity XPRIZE that may further catalyze the development of a thriving longevity industry; our readers already know something about it from Keith’s article, but, as an insider, is there anything more you could share with us, such as when the prize might launch or if more proposals are being evaluated?

We expect to launch next year, and the exact date will probably be announced during XPRIZE Visioneering in October. I am really looking forward to it, since it is a great big event where ideas for future XPRIZE initiatives are discussed. There are also lots of amazing people in attendance – last year, Pharrell Williams and Eric Schmidt were there, for example.

Besides the upcoming Longevity XPRIZE, are you involved in other XPRIZE initiatives?

Yes, I was also involved in the Global Learning XPRIZE, where I coached five finalists in the competition. The result of their work was to give children in African countries a tool to learn English (or their native language, Swahili) by themselves, without an adult, in just 12 months, using an app.

Speaking again of affordability, even if life-extension medicine eventually becomes affordable, we can’t expect that to happen overnight. How long, in your opinion, will it take before it’ll be cheap enough to be widespread?

Life extension is a very complex issue – if there were a simple solution, evolution would probably already have taken care of it.

I expect that various technological breakthroughs, scientific research, and the work of many people around the world (including our small team at Longevity Vision Fund) will collectively contribute to the continuous evolution of longevity and the prolongation of human lifespans. However, as I mentioned before, it would be impossible to predict when exactly this will happen and exactly how widespread we can make life-extension medicine.

Let me ask a few personal questions again. Many people, even life-extension enthusiasts, are not convinced that major breakthroughs will happen during their lifetimes. How about you; do you expect to “make the cut”?

I visualize myself living to 200, and whether I get to live to 200 or not, is arbitrary. The mindset of living to 200 myself stimulates me to live, work, and contribute to longevity to the best of my ability, since I am more passionate about improving the lives of others than focusing just on my own. As Peter Diamandis says, “the best way to become a billionaire is to help a billion people.”

Besides that, I definitely expect to see significant breakthroughs during my own lifetime and even bigger breakthroughs in the coming generations.

In your XPRIZE biography, I read that you’re a “happy co-founder of a diversified portfolio of 4 kids.” I take it as a funny way to say you’ve got four children; do you talk to them about life extension? What do they think of it?

I do talk about longevity and life extension to my two oldest kids: the 20-year-old and the 8-year-old. However, they see longevity as their father’s passion rather than something they are interested in as a topic. That’s understandable – hardly anyone under 30 thinks about aging.

As for my two youngest kids aged 5 and 1, I tell them “longevity bedtime stories”: tales involving “good” healthy foods, and avoiding “evil” sugar, sweet drinks, fast food, etc.

You make no mystery of your wish to live to two hundred. Is it just two hundred or at least two hundred?

To most people, both sound equally unbelievable, so with my binary thinking, I just focus on the number “200”.

Many people out there wonder what we’d do if we lived much longer than the current status quo. What would you do with that kind of extra time?

Adding an extra 25 years to our lifespans gives us fundamentally new options: spending more time with children and grandchildren, redefining our lives, getting new careers, and working on solving the world’s problems.

I would, of course, spend more time with my family and continue my work in solving the problems and diseases of aging. But this is a question that everyone can ask themselves. What would you do if your life were extended by a quarter?

As a final question, are there other causes than life extension that you find very important or are personally involved in?

Apart from focusing on doing good on a global scale, as with my work on longevity, I like to make a difference on a smaller scale as well. While it’s important to work on solving global problems, it’s just as important to connect and support communities locally. For example, every New Year’s, my wife, my kids, and I give away festive food sets to families in need. We started with 100 families, and last year, that number reached 300.

I would also like to end this question by thanking LEAF and, in particular, its president, Keith Comito. Thank you for your dedication in promoting life extension and for building such a fantastic and comprehensive longevity platform like LEAF!

Nicola Bagalà is a bit of a jack of all trades—a holder of an M.Sc. degree in mathematics; an amateur programmer; a hobbyist at novel writing, piano and art; and, of course, a passionate life extensionist. After his interest in the science of undoing aging arose in 2011, he gradually shifted from quiet supporter to active advocate in 2015, first launching his advocacy blog Rejuvenaction before eventually joining LEAF. These years in the field sparked an interest in molecular biology, which he actively studies. Other subjects he loves to discuss to no end are cosmology, artificial intelligence, and many others—far too many for a currently normal lifespan, which is one of the reasons he’s into life extension.

Why I Am Future-Positive on My Birthday – Article by Steve Hill

Why I Am Future-Positive on My Birthday – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by the Life Extension Advocacy Foundation (LEAF) on June 7th, 2019. In this article, Mr. Hill discusses how he feels great about being over 40 years old, instead of the depressing feeling that many tend to have on their birthdays, because he is very aware of how close medical science is to curing age-related diseases. He goes on in discuss, in his opinion, two of the most promising research methods being sought by various companies to defeat age-related diseases.

~ Bobby Ridge, Assistant Editor, July 7, 2019


Not so long ago, it was my 44th birthday, and I’ve finally decided to write something that I’ve been reflecting on for a while. To some people, a birthday is a cause for celebration; for others, it is viewed as a bad thing.

Yes, if you take the negative view, you could see it as simply a reminder of being another year older and another year closer to the grave. However, this is not how I see it; in fact, I think quite the opposite. I see it as another year closer to our goal: the defeat of age-related diseases due to the progress of rejuvenation biotechnology that offers longer and healthier lives.

From my point of view, viewing birthdays, or, indeed, the passing of time, as a positive or negative thing is largely a question of knowledge and understanding of the aging research field, which ties in with what I want to address today.

Knowledge is power

During my work as a journalist, people often ask me how things are progressing in the field. This is, of course, a perfectly reasonable and understandable question to ask. While I am always more than happy to talk about the field and answer this question, I also urge people to delve deeper into the field so that they can learn and evaluate for themselves rather than simply taking my word for it.

Our website, including the Rejuvenation Roadmap, is a good resource to start learning and to hear the latest news, as are places such as FightAging and the SENS Research Foundation website. Conferences such as Ending Age-Related Diseases and Undoing Aging are also valuable places to learn more about what is happening in the field.

Sometimes, I encounter people outside, but also fairly frequently within, the community who can be somewhat pessimistic about the field and its progress. It is perfectly natural to be cautious about the unknown, but there comes a point at which caution becomes unwarranted pessimism. The “Science Will Not Defeat Aging in My Lifetime, so Why Bother?” argument is a classic example of this, and much of this is caused by a lack of knowledge and understanding of the field.

The Latin phrase scientia potentia est, meaning “knowledge is power”, is particularly apt here. Knowledge and understanding allow us to better evaluate a situation or a proposal and reach a conclusion. It is hard to reach an accurate conclusion about anything without all the facts in place, yet I often see people doing it. Of course, there are always people who will not put in the time and effort required to learn about a topic properly, so they make predictions without all the facts, but there really isn’t much we can do about these people.

However, as advocates and supporters, we can do our best to learn about such things ourselves, and this will also come in useful when speaking to others about the field, as there is nothing like having a good understanding of the topic to help you convey it to others. That does not mean you need to become a biologist and understand things to such deep levels but even a solid understanding of the basics can be a huge help when it comes to engaging with others on the subject and also for understanding where we are currently progress wise.

Future-positive

This relates to a second question people often tend to ask me, which is if I think that they or we have a chance of living long enough to see these technologies arrive.

Obviously, no one can predict the future, so this question, by its very nature, is a tricky one to answer. I generally avoid being too specific on the timeframe in which we will reach the goal of longer lives through science, but I am optimistic that people in my age group, even perhaps older, have a reasonable chance of making the cut.

The reason that I am generally optimistic about the future is mostly that, as a journalist who speaks to hundreds of researchers, each focused on a part of the puzzle, I get an almost unique picture of the field. I can see the broader landscape and how and where things in the field or related fields connect or may connect in the future. A breakthrough in a related medical field may not have immediately apparent utility in aging research at first glance, but a deeper look could reveal hidden potential.

This fairly unique insight, combined with the knowledge that I have collected over the years working in the field, makes me fairly optimistic about the future and my place in it. As I have said a number of times in the past, the defeat of age-related diseases will not suddenly happen overnight; there is unlikely to be a single moment at which humanity goes from having no choice about aging to having control. It is far more likely that there will be steady progress, with incremental breakthroughs along the road, that will ultimately reach the goal.

Reasons to be cheerful

I would like to touch upon two of the most promising therapies that I am most interested in and believe may have a big impact in the near future (10-20 years) and that may help pave the way for major changes to how society thinks about and treats aging. Both of these therapies directly address one of the nine proposed causes of aging and thus if they work they have the potential to be transformative in healthcare. Of course, there are more therapies in development and at various stages of progress which also address the other causes of aging but these two are what I am most enthusiastic about presently. I urge you to explore the provided links to resources and learn more about each one.

Senolytics

No list of promising technologies would be complete without talking about the senescent cell-clearing drugs and therapies known as senolytics. Senescent cells are aged or damaged cells that should destroy themselves via a process known as apoptosis but, for various reasons, do not do so; instead, they hang around, sending out inflammatory signals that harm nearby healthy cells, block effective tissue repair, and contribute to numerous age-related diseases.

One proposed solution to these problem cells is to remove them by causing them to enter apoptosis, as originally intended, by using senolytic drugs and therapies. Removing these cells in mouse studies has produced some remarkable results, with mice often living healthier and longer lives as well as reversing some aspects of aging.

The race is now on to bring these drugs to people, and a number of companies are developing them right now. So far, UNITY Biotechnology has seen the most progress, and the company is already conducting human trials of its lead candidate drug (UBX0101) for the treatment of osteoarthritis. It has another candidate drug (UBX1967) closely behind; this drug is poised to enter human trials for the treatment of age-related macular degeneration, diabetic macular edema, diabetic retinopathy, and glaucoma. Based on recent comments from UNITY, we are anticipating the initial results of human trials in the next few months; hopefully, the news will be positive.

With the number of companies working on these therapies, it is fair to be optimistic about their potential to address multiple age-related diseases given that senescent cells are a proposed root cause of aging. You can also check out the Rejuvenation Roadmap to see which companies are working on senolytics and how they are progressing.

Partial cellular reprogramming

Cells can be reverted back to an earlier developmental state, known as induced pluripotency, using reprogramming factors, and this process effectively makes aged cells functionally young again in many ways. Ever since its first discovery, there has been a great deal of interest in this area of aging research.

The problem with inducing pluripotency is that the cell loses its identity and forgets what cell type it currently is, as it becomes a new kind of cell capable of being guided into changing into any other cell type, much like our cells during development. This is great for early human development, but as adults, having our cells forget what they are is bad news. Therefore, researchers have wondered if it is possible to reset a cell’s age without resetting its cell memory, and the answer appears to be yes!

Thankfully, during the reprogramming of a cell back to pluripotency, the cell’s age is one of the first things to be reset before the cell memory is wiped, and it appears possible to partially reprogram the cell so that only aging is reset. We have talked about the potential of partial cellular reprogramming and how it is similar to hitting the reset button on aging in a previous article, but, needless to say, if we can find a way to safely partially reprogram our cells, it could have a dramatic impact on how we age and may allow us to remain more youthful and healthy.

In terms of progress, partial reprogramming has already been demonstrated in mice, and now a number of groups, including Turn.Bio, the Salk Institute, Life Biosciences, Youthereum Genetics, and AgeX, are developing therapies based on partial reprogramming, which is essentially the resetting of cells’ epigenetic states (what genes are expressed) from an aged profile to a more youthful one, again directly targeting one of the proposed root causes of aging.

This approach is likely to be quite a few years away, but I think it is plausible that it could be in human trials in the next decade, and it is probably the approach that interests me the most in the field.

In closing

The truth is we cannot predict the future because it is not set in stone, so we cannot be totally certain if or when rejuvenation technologies will arrive. The best we can do is learn as much as we can about the field and try to reach a reasonable conclusion based on the situation as it is now.

The field is advancing steadily, and we should be optimistic but not complacent about progress. We should be mindful of being too negative and, equally, of being too positive without ample justification. Blind optimism is as bad as blind pessimism, and we should always strive for informed optimism.

That said, given the progress being made, I am optimistic about my chances based on the evidence to date. This is why I do not mind birthdays and why I find them positive experiences rather than negative ones. Arm yourself with knowledge, and perhaps you too will agree with me and understand why I am future positive.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity, created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

A Chance Encounter in a Graveyard – Short Story by Nicola Bagalà

A Chance Encounter in a Graveyard – Short Story by Nicola Bagalà

Nicola Bagalà


Editor’s note: The U.S. Transhumanist Party features this short story by our guest Nicola Bagalà, originally published by the Life Extension Advocacy Foundation (LEAF) on August 10, 2018, August 17, 2018, and August 14, 2018. In this story, Mr. Bagalà describes the experiences of a man discovering how salient it is to NOT biologically age and die. This was originally written in three separate parts, but combined in this single article. I hope you find commonalities in your life while reading this story so that you can be motivated in helping our species cure all diseases through innovations in science and technology.  

~ Bobby Ridge, Assistant Editor, July 6, 2019

This is a fictional story about a man realizing for the first time, under rather unusual circumstances, that he has a deep desire not to age and die.

Part I

It’s been a few months already, yet that day still feels like yesterday. I am still not convinced that I didn’t lose my mind that day, and even if I didn’t, it’s changed my thinking quite a bit.

I was in a green grove in the local cemetery, sitting on a bench. As it is the piece of nature closest to home, I used to go there quite often. A small group of men, all at least in their 40s and wearing black suits and ties, had passed by just as the bells in the nearby church began ringing.

A new member joins the club, I thought, meaning the graves all around me.

Spending eternity in a place like that mustn’t be that bad, I observed, as another, larger group of people was heading presumably to the same funeral as the previous group. There were no preoccupations, no problems, only greenery and quiet as far as the eye can see; nothing but birds singing, squirrels slipping away from tree to tree, and people strolling as they came to see their dead. There certainly are worse things than this, I said to myself, especially if you’re alive.

“Very nice indeed, or so it would seem,” a voice from behind suddenly said. The person then came to sit right next to me as I looked at who was talking. I looked her up and down for a moment, trying to establish whether it was safe to remain seated or if I should spring up to my feet.

It was a really beautiful girl, about twenty years old. She had red hair reaching to her shoulders and icy blue eyes. She was leaning forward, her elbows on her knees, staring at the graves before us; she didn’t seem to care about my startled look. Judging by her attire, I’d say she too was going to the funeral, although she seemed to be in no rush to go anywhere.

“Indeed, I’m not,” she said, as if she’d read my thoughts, still looking at the headstones. “It’s pleasant here.”

“I beg your pardon?” I finally stuttered.

“It’s pleasant,” she reiterated, slightly turning her gaze towards me for a moment, and then back to the graves. “Isn’t it? It looks like a nice place.”

“Undoubtedly,” I nodded, hesitantly. She said nothing. She had a slight, intelligent-looking smile, which made her look somewhat pleased with herself, though not arrogant. It was as if she were waiting for me to say anything, as if she knew that I had something to ask.

The bells rang again.

“I’m sorry, miss,” I commented, uncertain, “but did you mean that the graveyard is nice or just that it seems to be?”

“It depends on your point of view.” I would have asked more, but she continued. “Are you in a hurry to go?”

Her question caught me off-guard. “Me? No,” I stammered, thinking for a moment she must be one of those young girls trying to hit on men one or two decades older. “It’s Saturday afternoon, and—”

“That’s not what I meant,” she interrupted me, looking away from me towards the church.

“Then what?” I asked, even though I should perhaps have left, annoyed by the way she was talking to me.

“You’re right,” she replied, apparently ignoring what I had asked her. “It’s a quiet, pretty place, perfect if you need to relax or reflect. However, I wouldn’t like spending here more than an hour or two. How about you?”

“Well,” I said, asking myself once again why I was even still having that absurd conversation, “that would depend on what else I had to do at—”

“How about if you were dead?” she interrupted again, still gazing at the many headstones, as if I wasn’t even there. “You wouldn’t have much to do if you were dead. How much time would you like to spend here, if dead?”

“What a silly question,” I replied firmly, trying to conceal how her mentioning my own death had upset me somewhat. I told myself that it was an absolutely normal reaction, and her question was really silly anyway. “Excuse me, miss, but if I’m dead, then it’s obvious I’ll be spending eternity in the graveyard, be it this one or another.”

“I didn’t  ask you how long you’d be here,” she clarified. “I asked how much time you’d like to spend here.”

Her remark seemed to suggest she wasn’t too sound of mind. I quickly glanced around, desperately looking for people who might be short of a crazy relative on their way to paying the last respects to the dearly departed. Not a soul was in sight—except those that the graves were standing in for.

“I doubt my preferences would make any difference,” I said shaking my head, smiling as I would to anyone too mentally unstable to be safe to contradict.

“That’s true,” she nodded. “Then again, it doesn’t matter, does it? It’s such a pretty place that one would gladly spend eternity in it. I mean, there are worse things than this, especially if you’re alive.”

As I noticed the similarity between her words and my own earlier thoughts, I felt a lump forming in my throat. I was tempted to ask her what the devil she wanted from me, but then I told myself there was no reason to lose it for a simple coincidence, however disturbing.

“Indeed,” I nodded nervously.

She took a few steps toward a tall headstone nearby and knelt before it, seemingly to read the epitaph. That would’ve been the perfect chance for me to take my leave, but she managed to anticipate my move once again.

“Of course, there’s a small problem with this theory,” she said distractedly.

“What would that be?”

“If you’re dead, whether the place is quiet or pretty doesn’t matter to you.”

“Of course not,” I said, starting to feel fed up with all those truisms.

She turned toward me, feigning perplexity. “Then why did you agree with me, when I said one would gladly spend eternity here?”

“That’s just a set phrase,” I replied. “Things people say.”

“Correct. Good.”

It felt as if she thought she was the teacher and I the schoolboy.

“But anyway, what does it matter?” I went on, feeling I should retort something. “You just implied that if you were buried in the worst place in the world, you wouldn’t care in the slightest.”

She turned again, with an almost naughty smile, and she moved closer to me. “Normally, people don’t talk to me like that.”

What cheek! As if she hadn’t been agitating me this entire time!

“They don’t like talking about it, but it’s almost as if they feared me, you know?” she continued. “Almost reverentially, one would say.”

Who wouldn’t be afraid of such a nutter, I thought.

She turned abruptly and slowly started walking away with her arms behind her back. After taking a few steps on the grass, she asked out of the blue, “Say, are you afraid of death?”

“Excuse me?” I said, even though I had got that perfectly.

“You heard me,” she replied promptly, as she kept walking slowly away from me. I kept following her, telling myself the only reason I was doing so was that, clearly, she was disturbed, and it would be irresponsible of me to just leave. I was convinced that she should be attending the funeral at the nearby church. She was probably a relative of the deceased, and her relatives were understandably too shaken up by their loss to notice that she wasn’t there. I wasn’t certain I was right, but even if I was, I certainly couldn’t just pop up and interrupt the funeral to ask whether someone was short of a daughter or a sister. I decided I’d wait until the end of the ceremony, as it probably wouldn’t last much longer. Meanwhile, I’d try to understand whether my intuition was correct.

“So?” she insisted. “Are you afraid of death or not?”

“If you really want to know, I’m not,” I replied. “I see no reason to worry about something I cannot be aware of in any way.”

“You keep answering questions I never asked. I asked if you’re afraid of death, not of being dead.”

“So you mean the act of dying? I’m not afraid of that, either. Granted, I’d rather it be painless and not too drawn-out, but—”

“I really cannot take into account individual preferences. Be as it may, you say you’re not afraid?”

“I’m not,” I reiterated, ashamed of my own apprehension.

She hummed pensively. “I see. Then what reason do you have to sugar the pill?”

“What?”

“Your set phrase. One of those things people say, that which we were talking about a moment ago. There are worse things than spending eternity in such a nice place. Why do people say things like that?”

Now I was starting to see things more clearly. She just had to be a close relative or friend of the person whose funeral was taking place right now. She must be so much in shock that she couldn’t even join the mass, her pain and anger fuelling all the bizarre things she kept saying. Notwithstanding that, she mustn’t have been too sane even prior to her loss.

“They say them to console who suffered the loss of a loved one,” I replied in an almost fatherly tone.

“How about to dispel the fear of one’s own death?”

“Well, that too, I guess…. In some cases…”

“You just told me you’re not afraid of death.”

“Indeed I’m not, but—”

“Then why were you thinking that it wouldn’t be too bad to spend eternity here? Why do you need to tell yourself that if you’ve got no fear to dispel or people to console?”

I stood speechless.

The graveyard was almost entirely silent, except for the incessant chirping coming from the treetops. I couldn’t help but wonder whether that girl, very weird at best, was just unbelievably perceptive or if she really could read my mind. Did she know that I had indeed thought that before, or was that just a lucky deduction?

I really didn’t know what to tell her, nor did I like the idea of having to justify my unexpressed thoughts to a complete stranger; thus, I tried to change the subject. Once more I had an uncomfortable feeling that she knew I was in a tough spot and wasn’t expecting me to answer her question.

“Are you here for the funeral?” I asked, bobbing my head to point at the church.

“No,” she replied.

“Was it a relative of yours, or…”

“I have no relatives, nor anything more to do with this funeral.”

“Anything more?” I asked puzzled, although ever more convinced she was lying, denying the truth to deny her pain. As she was used to, she ignored my question and changed the subject.

“Come,” she said. “I want to show you something.” She then headed off to a trail among the graves, as sure about where she was going as the cemetery’s caretaker would be, without even turning to see if I was following her—which I was, though in frustration.

She led me to an eye-catching headstone with a low-relief angel holding his forehead in despair. There was an inscription, too, which I guessed was a quote from the Bible or the Gospel.

I waited for her to say anything, but as she kept mum, I resolved to ask: “So?”

“The inscription. Read it.”

I couldn’t hold back a short grumble, annoyed as I was at her manners, but then I began: “I am the resurrection and the life. He who believes in Me will live, even though he dies.” Once more, she kept silent, so I pressed her: “Well?”

“Do you believe that?”

“No,” I answered, happy that there appeared to be at least one thought in my mind she hadn’t already read. “I’m not a believer.”

“A great deal many others are, though.”

“Yes. So what?”

“Millions, billions of people believe, or believed, that death isn’t the end, and that some kind of afterlife is waiting for them beyond the grave. They believe there’s a place where they’ll somehow be able to live forever without pain or afflictions. If overcoming death is such a cornerstone of long-lasting religions with so many followers, then maybe the set phrases you’ve been saying are meant to console those who say them, rather than those who listen to them, in more than just ‘some cases’.”

“I never said people aren’t afraid of death,” I objected, fearing that I was clutching at straws. “I just said I don’t think that’s very rational, that’s all. People have a lot of irrational fears.”

“And as you said, you’re not afraid of death. That wouldn’t be rational,” she said, nodding slowly, as if she were finally understanding what I had been trying to tell her. “So,” she went on before I could say anything, “if I offered you, here and now, a quick and painless way to die, just as you wish, you wouldn’t be against that, would you?”

My heart skipped a beat as I felt adrenaline rushing down my body like a waterfall. She was crazy, all right, but just how crazy was she? Anyway, as weird as she was, I didn’t believe she was dangerous, nor did it look like she had anything with her that could be used as a murder weapon.

“I said that I don’t fear death,” I hurried to clarify, trying to keep my composure as much as I could, “not that I’m looking forward to death. I don’t wish to die now, but I don’t fear the moment of my death.”

“So you’re saying you would refuse my offer,” she concluded, nodding. “However, given that you don’t fear death, would you refuse my offer as you would if I was offering a meal you’re not in the mood for? Perhaps with a smile, a kind gesture of the hand, and a ‘no, thank you’?”

“Do you realize it’s homicide you’re talking about?” I said drily and quietly, trying to appeal to any shred of rationality she might still possess.

“How interesting that you should appeal to the outrageousness of homicide in a conversation about the irrationality of fearing death.”

Once more, I didn’t know what to counter, but whatever she might be getting at, I had no intention of letting her win the argument. Something unknown inside me was pushing me to prove her wrong at all costs, to show she was mistaken. I passed a hand on the back of my neck, casting another look at the church as I wondered how bloody long it would still take for the funeral to come to a close. The girl, always as cool as a cucumber, resumed her stroll among the graves.

“Listen,” I told her, trying to show compassion, “I understand the pain you must have felt when—”

“I already told you that I have no relatives,” she interjected. “He did, though.” She stopped before another gravestone. “Read his birth and death years.”

The inscription said 1946 and 1951, respectively.

“I see,” I said. “He died still a child.”

“A real tragedy, was it not?”

“It certainly was,” I conceded. Despite her stubborn denial, I thought that contorted discourse might be her way of telling me her story. Perhaps, the person she’d lost had died an equally early death.

“Is it irrational to fear tragedy? When this child realized he was about to die, was it irrational of him to be afraid? What about his parents?”

Since I had met her, each and every of her words had been uttered in the calmest and most peaceful of ways. Not once had she lost her aplomb nor betrayed any anger or sorrow. There was no enmity in her words but no indifference either. From where she was standing, I thought, she was simply discussing a topic that interested her very much, displaying exemplary cool-headedness and firmness.

“This is a special case,” I observed. “His death was very much premature.”

Without ever taking her eyes off me, she moved to a couple of graves a few steps away. “He was 67 when he died,” she said pointing at the epitaph on one of the headstones. “Was he ‘ripe’ enough for death that his passing cannot be considered a tragedy?”

“I… I know nothing about this man,” I attempted to justify myself.

“He took his own life. His health was deteriorating, and he could not cope. So, was this a ripe enough death?”

“How do you—”

“I just know.” The girl pointed to the grave next to the man’s. It bore the same family name as his. “After he died, she lived fifteen more years, though it was no longer the same without him. She had a heart attack, at age 85. Was this a tragedy, or was she old enough?”

“Look, what do you want me to say?” I burst out, spreading out my arms. “I’m sorry for these people, but death is a part of life. You must learn to accept it.”

“Not my problem,” she replied, puzzlingly.

“Oh, isn’t it now?” I asked, simply unable to conceal sarcastic defiance. I sat on the border of a flower bed, shaking my head in frustration and disbelief.

“No, it is not,” she replied, barely shaking her head. “Besides, not all that is part of life is accepted without question. For example, infant mortality. It was a part of life until you found a way to eliminate it almost entirely. Most parents of all times had to accept that, probably, some of their children would never live to be grown-ups. Yet, it is no longer so.”

“Whatever do you mean ‘until you found’? Are you an alien?”

“No,” she said, not bothered in the least by my sarcasm.

“Listen,” I said as I sprung up, determined to make things clear once and for all. “I don’t even know your name, and—”

“You do.”

“No, I don’t,” I went on undaunted, “and I’m getting tired of you acting mysterious. I tried to be patient, because despite your obstinate denying it, it’s glaringly obvious that you suffered a tremendous loss recently—quite likely the person in that coffin right now,” I said pointing to the church once more. “I am sorry for your loss. I mean it. I must admit that façade of absolute tranquillity you put up could fool anyone, but I can tell you’re shaken up. Do you want me to say that death is not a nice thing to think about? Fine, it isn’t. But it is inevitable. And at the end of the day, that’s good, because just like many other unpleasant things in life, death is also necessary.”

“It happens every time,” she nodded musingly.

“What?”

“Every time you begin to realize that death is nothing like the indulgent metaphors you use to describe it, thinking of its inevitability pushes you to look for other ways to justify it. Bearing with a horror that is both inevitable and useless would be too much; and as it can’t be but a horror, you need to find it a purpose.”

“You’re blowing it out of proportion,” I objected firmly. “Granted, diseases, wars, and calamities cause useless deaths. They are horrors, I agree; that’s not the natural end of a human being, and indeed we do our best to avoid those deaths. But the circle of life must close itself for the common good. That’s not a horror but only the natural order of things. An endless life would also be meaningless and would wind up being a sentence to eternal tedium. Besides, it would be so problematic on so many levels I can’t even begin to count them.”

“What’s a human being’s ‘natural end’?” she asked, completely unimpressed by my speech.

I snorted in annoyance. “You’re just pulling my leg now.”

“No.”

“All right, if you really want to play dumb. The natural end of human beings is death by aging. We are born, we grow up, we live our lives, and finally we walk into the sunset. You can see this kind of cycle everywhere. Without it, life itself wouldn’t be possible.”

“Are you sure,” she inquired, “that what you’re talking about isn’t just the umpteenth item on the long list of obvious and incontrovertible truths that were such only until someone had the effrontery to prove them false?”

“What the devil are you—”

“Can you claim without fear of contradiction that it is absolutely necessary for everyone to die, sooner or later, in order for life to continue? Are you ready to prove to anyone old enough that their death is as necessary as is due? If it was possible to avoid age-related decline and death, would you oppose that on the grounds of your convictions, thereby sentencing to death every human being present and future? Are you so sure of your stance that you would deem reasonable, right, or acceptable, to ask everyone to sacrifice themselves in its name?”

Under any other circumstances, I would have thought that this rapid-fire sequence of questions was pompous, arrogant, and rhetorical. I would have laughed right in her face, called her haughty, and left. However, she had spoken candidly, without an ounce of arrogance or conceit. She had uttered those words with the same tone as any other word since I had met her—the tone of someone patiently waiting for you to realize that maybe you share the same views as her.

“I don’t feel like I can make this kind of moral judgement,” I stammered after a moment. “Maybe… Maybe I wouldn’t be so sure about it, but anyway…”

“Yes?” she encouraged me.

“…I don’t think it matters. I don’t think anyone would want to live forever. Yes, yes, I know what you’re about to say: myths, stories, films, and what have you have been talking about eternal life for centuries. I know you were about to say that; I figured out who I’m dealing with by now.”

“Not yet,” she smiled, “but you’re getting there. Please, do go on.”

I didn’t even attempt to understand what she meant, and I continued: “In fiction, the gift of eternal life appeals to many. It’s an attractive prospect, but it always turns out to be a double-edged sword. Nobody who has seriously reflected on it could ever really want to live forever. Sooner or later, we would lose motivation; there would be nothing new to do, see, or learn. Knowing that life is endless would make us unable to appreciate it, just like we would be unable to appreciate a nice sunny day, if all days were.”

“How do you know?”

“It’s obvious!” I stammered again, angrily, after a few moments spent looking for a more convincing argument to no avail. “After a century or two, what do you think there would—”

“If two people having this same conversation three centuries ago had been alive today, they would have had innumerable things to do, see, and learn that weren’t even imaginable at the time. Are you sure that human progress on all fronts has already come to an end? Do you believe that life can be appreciated only if it’s short? Maybe these are just assumptions that you make to help you banish your fear of death from your mind. If there was a moment when one is tired of life, wouldn’t you rather decide for yourself when this moment has arrived? Death may come when your desire to live is still strong or long after you had already lost it, without asking for your opinion first—just like I didn’t before I began this conversation.”

Something in the way she pronounced that last sentence sent shivers down my spine. Speechless and short of breath, I peered at her for a few moments, trying to understand what was the answer to what I had thus far avoided to ask her. She held my stare without flinching. Finally, I resolved to ask.

“Listen, what the hell do you want from me?” I burst out, surprised by the hatred I felt for her. “Why don’t you go and dump your pearls of wisdom on somebody else?”

I had to defend myself. That’s what I felt. That was the reason for my hatred. I didn’t know why, but I felt threatened. The threat could be averted only by putting an end to the conversation and forgetting about all that bloody nonsense.

“There is only you and me here,” she noted, as if she was pointing out the obvious.

Indeed, the cemetery was absolutely deserted, and thinking about it, it didn’t seem as if anyone at all had passed by during our conversation, which I had estimated to have lasted about an hour. I must have got carried away more than I thought, since I hadn’t even noticed that the nice blue sky of that day had turned a leaden shade; roaring thunders announced an upcoming storm.

“Then go back to your relatives at the funeral,” I went on irritated. I was no longer showing her any respect, as I thought she had proved herself unworthy of it. “What’s taking them so long?!”

“There is no funeral,” she said. “There never was.”

“I’ve got enough of your rubbish!” I growled, quickly moving closer to the church door. “Of course there’s a funeral, look at the…”

The funeral announcement was gone, as were all the funeral wreaths. There was no sign that anything at all had happened in that church on that day.

“What the devil—they couldn’t just finish and clear out that quickly without us noticing!” I said nervously, looking all around the church for any sign that anyone at all was there. “They must have taken out the coffin, how could I have missed that? We’ve been here the whole time!”

She followed me, and looking at me compassionately, she said: “I told you. There was never any funeral.”

“Rubbish!” I shouted as a lightning bolt loudly tore the sky open. I probably looked much crazier that she was, and I was surprised that she didn’t seem to be afraid of that.

“What the hell do you want?! What the hell do you want?!” I shouted again.

“I only want you to understand something that, deep inside, you already know.”

“What? That death is horrible? A tragedy? A disgrace? That there is some kind of holocaust going on without anybody noticing? What do you know if that’s what I think?”

Once more, she stared at me silently. Her silence was worth a thousand words.

“Moonshine!” I shouted in her face. “Everything is completely normal, and it’s perfectly fine as it is! Am I going to be dead someday? Everyone is? Fine by me! There is no holocaust, no disgrace, and no tragedy!”

“I wonder if you would still think that,” she mused, asking herself more than me, “if rather than by headstones we were surrounded by the poor bodies buried underneath.”

I didn’t know why, but suddenly I felt terrified that that horrible scene might be happening right behind me, as if driven by some kind of supernatural force. Petrified and short of breath, I stood silently, listening to her once more, jolting at the slightest sound coming from behind.

“It gives life its meaning and makes you appreciate it, spares you the tedium of too long an existence, even begins the afterlife… it’s the end of a cycle, a relief from the chores of life, a sunset, a quiet and peaceful rest, an eternal sleep…” The girl chuckled. She was wearing the same benevolent expression she always had, which made her even more unsettling. I said to myself that, if the dead were really rising from their graves behind me, I’d rather know than let them take me by surprise.

I turned abruptly.

The headstones were exactly where I had left them. I sighed deeply, in relief, slightly shivering at every blow of the cold wind from the upcoming storm.

“Is this how you imagine me?” I heard her ask from behind.

In that moment I was sure that, had I turned, I would see the girl transformed into a horrible cadaver. I swallowed hard, and once I found the courage, I turned quickly towards her. Luckily, I was wrong again.

“You really don’t come across as someone who doesn’t fear death,” she commented.

The dim glimmer of rationality left in me insisted that the girl was simply disturbed, and I was just letting the circumstances deceive me. Yet, I could not resist the temptation to finally ask her something that, in truth, I had already been tempted to ask her long before.

“Are you… are you death?”

“Is this how you imagine me?” she asked again, in a particularly eloquent tone.

It could not be. None of it made sense. How could such a beautiful girl ever be—

“I am not as beautiful as you think,” she chuckled almost timidly, looking away for an instant. “I am not a release, a sunset, quiescence, or an eternal sleep. I am nonexistence, oblivion, nothingness, annihilation, the loss of yourselves, destructor of possibilities and dreams. I don’t give life meaning, nor do I give anything; I take without giving. I am what is when you are no more. I am what is when even hope is lost. I am the end of all.”

“It can’t… It cannot be…” I stubbornly denied, shaking my head in panic. “That’s just nonsense… You… You’re crazy!” Quickly, I moved away from her to the exit, walking backwards to keep my eyes on her. She showed no intention of following me. “Stay away!” I ordered, regardless, pointing my finger at her threateningly. “I want nothing to do with you! Stay away!”

“I am glad you finally understand it,” she said, almost relieved.

I quickly turned around and ran away. I crossed the exit gate and kept running, and without ever looking back, I headed to the closest tram stop. I didn’t need transportation to get home, but I had an urge to get far away from that girl, whoever she might be. The passengers on the tram looked somewhat alarmed by my hasty and disorderly entrance, and were casting fleeting and diffident glances at me; regardless, the sight of normal human beings felt like being able to breathe again. I hurriedly collapsed on the first available seat, and only then did I notice with great stupor that it was late at night. I had no idea how that was possible; it was barely past midday when the girl approached me, and there was no chance it could be that late now. Yet, according to my wristwatch, it was past 10 P.M. To hell with it, I didn’t care; all that mattered was getting far away from that unsettling nutter and getting home as soon as possible. I took a deep breath and tried to relax, mentally calculating the stop at which I should get off. I couldn’t help looking around, every now and again, just to make sure she wasn’t there, among the passengers, observing me with that disturbingly benevolent air of hers.

He might have run away from the girl, but he cannot run away from himself.

Part II

I feel ashamed admitting to this, but I proceeded with wariness all the way to my door. That late at night, I didn’t meet anyone in the hallways or in the elevator. At first, I didn’t even want to take the elevator, as I was afraid that the girl might suddenly appear before me when the doors opened as I got in or out; however, for some reason, the idea of taking the stairs felt even worse, nearly terrifying. After hesitating some, I chose to take the elevator. Once I reached my door, I inserted the key in the lock, and after a moment of hesitation, I began turning it. At each turn, which echoed sinisterly in the hallway, I stopped as if to check that the sound didn’t attract the attention of God knows what supernatural creatures lurking in the dark. Absolutely nothing looked different than usual, yet I felt like a character in a horror movie.

I opened a crack between the door and the frame, stuck a hand in, and frantically searched for the light switch on the wall. “Finally home,” I said in an annoyed and embarrassingly loud and shaky voice to no one in particular, while still searching for the switch with no success. Once I found it, I flicked it, and as soon as the light went on, I pulled the door wide open, ran in, and finally slammed the door shut behind me.

I stopped on the doorstep for a moment and looked around, making sure no one was there. I pushed open the sliding door of the coat rack all of a sudden, to catch by surprise whoever might have been hiding in it; relieved that nobody was there, I hung my coat. I took off my shoes and went to the restroom, while still exploring my surroundings guardedly, trying to convince myself I was now calm and no longer afraid.

I washed my face, trying not to look at the mirror for fear that it might show one reflection too many.

Oddly, I wasn’t hungry at all, but I did feel like having a hot drink. I fixed myself a hot chocolate. I left the boiling hot mug on the table and sat down.

That girl was not death. She couldn’t be. Death is not a creature or an entity; it has no legs or arms, and it does not speak. It’s just an abstraction, a metaphysical concept, the name we give to the status of a living being that is no longer such. She was just a poor devil who had lost many of her marbles, or maybe she was shocked by the death of a loved one, or both. Granted, many sinister and unsettling coincidences had happened, and at the end of the day, I am quite impressionable, but it had all been just a trick of fate, nothing more. I wouldn’t be the first person to lose track of time, not notice a storm coming, or just plain not pay attention to what was going on around me. The girl wore black, but maybe she wasn’t there for a funeral. Maybe the funeral was over without me noticing it, or maybe it was true that it never happened—after all, a few suits and ties headed towards a church don’t necessarily mean that anybody died. I wasn’t even sure that I had actually seen any funeral announcements or flower wreaths.

It was an interesting story to tell at my next Halloween party, nothing more.

It was really disturbing how she seemed to be able to read my mind. She had replied to my questions or objections before I could even finish saying them in more than one occasion—sometimes, before I could even finish thinking them up. I’d rather believe she was absurdly intelligent, or even a telepath, than accept that she might actually be death.

Even assuming she actually was death, why would she come to me and speak ill of herself? To persuade me that death is an evil and we should stop sugar coating it? To what end? What would she expect me to do? To “kill” her where she was standing and set the world free from death?

Ridiculous, I thought to myself, shaking my head.

At any rate, that’s not what death—I mean, the girl wanted from me. In her words, she wanted me to understand something that, deep inside, I already knew. But I didn’t share her views at all; I mean, death is part of the natural order of things, I told myself, and even though hardly anyone is happy to die, that’s just the way it is. Death is necessary. Sure, I must admit that the whole of human progress hinges on the search for ways to improve quality of life and avoid death for as long as possible, and there is no reason we shouldn’t prevent deaths that actually are preventable or that happen too soon; that’s why doctors, hospitals, and safety measures exist in the first place, but…

Too soon, I repeated mentally. She had stressed that point a lot. I stood up, leaving my chocolate to cool down on the table, and I took a few steps towards the window, where I stopped to look at the downpour I had barely managed to avoid.

When is it “too early” to die? In your thirties? Forties? Sixties? I had never thought about it before, but now I couldn’t help but wonder about something that the girl had asked me. Suppose for the sake of argument that we didn’t grow old; imagine that we just grew up and that our health didn’t inevitably begin deteriorating sooner or later. Would we still think it isn’t “too early” to die at age 80? As a matter of fact, one might think that the reason why we normally think it is acceptable to die after your seventies is that it just happens and we can’t do anything to prevent it. Maybe it is not because of wisdom that we accept death at later ages without feeling outraged and without putting up a fight, like we do in the case of “premature” deaths; maybe we are just putting a good face on a really bad game.

No; no. Normally, the average lifespan is more than enough to live your life as a normal human being; it’s more than enough for you to grow up, go to school, get a job, and start a family, for example. Though it is also true, I was forced to admit, that human life is structured as a function of its duration and our health at every age. If we were always perfectly healthy, we would have no need to plan for old age, because in a way, it would never come. Maybe retirement would turn into just a holiday of a few years, and after your batteries are charged again you would be able to start over, perhaps in a different environment or even a new job, maybe.

What about the traditional milestones dictating the rhythm of our lives? Are they all one can aspire to? Is your life complete once you have had a career and grandkids? Is that time to die? What about people who never managed, for one reason or another, to do all they wanted to do before death? If death really must come, why must we first endure years of constant decline and deterioration—not only our own, but also that of our loved ones?

These issues had always seemed to be too far into the future to concern myself with them, but then I realized that, one day, they would be my problem too. It’s not like I didn’t know it; I did. Yet, somehow, the notion hadn’t really sunk in. I had always felt as if there was infinite time between me and old age. Being old and diseased, slowly heading to the grave, had always seemed to be somewhat of an unlikely and fanciful occurrence; laughable, even, and I laughed at it more than once. I had always thought that I laughed at death because I wasn’t afraid of it in the slightest, but now I was growing more and more suspicious that, in truth, I might have been whistling past the graveyard all along.

I suddenly moved away from the window and grabbed the mug on the table, hoping that a few sips of chocolate might help me calm down and ease the pain coming from the lump that had formed in my throat. Swallowing was hard and hurt, as if a tangle of old, withered knobby roots ran through my throat. My breath was heavy and labored, my hands were shaking, and my wish not to be left alone was so strong that even the company of the very girl who had unleashed this nightmare would have been preferable to the solitude of my flat.

I shook my head repeatedly. I wanted nothing to do with any of this. I didn’t give a damn whether the girl was right or not, nor did I care whether I agreed with her or not. All that I wanted to do was to put the lid back on Pandora’s box and bury it deep under the ocean so that it could never be found again. I wanted my old life back, the one I had and was perfectly content with up until that last, cursed morning: my job, my friends, the usual rhythms and milestones that everyone goes through. The ones that everyone goes through because everyone does and no one has much of a choice.

She’d planted the seeds of those thoughts in my mind, and they kept blossoming, nullifying my efforts to extirpate them and convince myself that I was as happy with the finitude of human life as I always had been; anxiety had me in a tight grip as I realized that I was no longer able to believe that old lie. Pragmatically, I told myself that, whether I liked it or not, old age comes for everyone and is inevitable; torturing myself like this would have no point. Debating whether or not it was right or desirable for every life to be abruptly terminated after years of deterioration would accomplish nothing but ruin the time I had left before deterioration would begin for me. I simply had to get over this.

Maybe, the girl would have said that this too was sugaring the pill.

I was exhausted, anxiety eating me alive and thoughts tangled up. Like a huge spiderweb, the more I tried to break free, the more I was enmeshed. I took a sleeping pill and resolved to put an end to that terrible day. The next day, I figured, I would wake up serene, as if nothing had ever happened.

Part III

Right after you wake up, there is a brief moment when you don’t yet know how you feel. That Sunday morning, that moment was even shorter than usual. The same anxiety as the previous night assailed me even before I could get out of bed.

The clock on the shelf said it was 11:30. I had slept almost 12 hours straight, but I wasn’t rested at all. Tired and depressed, I got up with difficulty, with a constant feeling of imminent catastrophe. I cast a glance out the window, and I noticed that the sky was clear and bright again. Upon closer inspection, I noticed the streets too were perfectly dry, as if it hadn’t rained for days. Indeed, the sun seemed to be very hot.

Near the sink was dishware that I hadn’t noticed the night before; I must have left it there at least since Friday night. I hoped some coffee would help cheer me up at least a bit, and I took a mug from the cabinet without even looking.

I left the coffee maker grumbling on the stove and went to wash my face. I looked terrible, which was no surprise, since I had had a terrible night. My sleep had been studded with horrible nightmares, although I hadn’t woken up screaming; rather, I’d been tossing and turning all night, moaning in my sleep nearly incessantly. I recalled a labyrinthine indoor cemetery; people dying of old age all around me, claiming to be very happy about it while I desperately tried to make them understand it was wrong; me and the graveyard girl, together somewhere in my old high school, as if we were classmates; me assisting my mother on her deathbed, listening her accusing me to make excuses for something; and many others which I thankfully almost didn’t remember at all.

I went back to the kitchen to pour my coffee, noticing in passing that I was using the same mug as the previous night. Apparently, I had been so much in shock that I wasn’t even aware of washing it and putting it back in the cabinet.

I drank my coffee and managed to push down a few biscuits. Not only was I still anxious, I hadn’t changed my mind either. That unexpected and visceral desire to avoid old age and death, and the realization that no stale moralism would be enough to extinguish it anymore, were still there where I had left them the night before. At the same time, I had a second, equally strong desire that the former could somehow disappear and take my anxiety down with it, setting me free from that apparently insolvable dilemma.

For some reason, I had an urge to check something on the Internet. According to statistics I found after a few moments spent searching, about a hundred and fifty thousand people die every day, of which about a hundred thousand die of old age. I realized that out there was an army of people who, just like me until the day before, didn’t think that the loss of those hundred thousand lives was a problem at all; rather, they probably thought that it was good that most people died of old age; otherwise, they would have died of something else and thus “prematurely”. This army of people was basically shrugging at two thirds of all deaths that happen every single day. Maybe there really was a constant holocaust to which no one was paying attention.

I backed away from my computer. I was blaming people for their indifference, but what else could they do? They were right: if you do not die of old age, it’s because you died of something else first. What was the better option? There didn’t seem to be a third one, and nearly everyone would choose to die later rather than sooner. The girl, I said to myself, would probably have said that this was a sign that the idea of dying is much more disturbing than people like to admit, and it upsets far more people than we think. Apparently, showing distress was acceptable only during a funeral; in any other circumstances, death is either ignored or justified, at least when it comes to death by aging.

The girl indeed.

I really didn’t think I would be able to talk about this with other people without coming across as a lunatic; I myself had thought that the girl had lost her mind. I was full of doubts and questions, and I wanted nothing more than to put an end to that oppressing anxiety. The previous night, I had screamed in her face that I didn’t want anything to do with her any more, but now I felt that, as crazy as she might be, the girl was the only person I could talk to about this. She might be able to answer at least some of the very questions that she made me ask myself.

The problem was that I had no way to find her. I had no idea who she actually was, what her name was, or where she lived. There was no way to trace her. The only thing I could think of was going back to the graveyard, hoping she was still there for some reason. I knew that this was a forlorn hope, and even if I did find her again strolling among the graves, I had no idea how she could actually be of help. I doubted she had any idea on how not to die of old age without dying of something else first. Regardless, I wanted to see her. It was worth a shot.

I left home, heading again to the graveyard. The day was even hotter than I had imagined, and as I had observed before, the flower beds were so dry that it really didn’t seem like it had rained at all during the night. On my way to the graveyard, I noticed that I looked at people differently, whether they were chatting with acquaintances, jogging, or just annoyed because they were late for the bus. It was a day like any other in the life of those people, and probably none of them spent much time thinking that sooner or later those days would be over or that health is in short supply. Equally probably, I thought, nearly all those people would agree that, from their perspective, none of those things was a problem. This thought made me feel as if I were the only sane person in a loony bin—which, paradoxically, led me to question my own sanity.

Then again, if those people had realized what I realized, wouldn’t they just end up like me and become prisoners of their own anxiety and of the thought of being stuck in a horrible situation with no way out? Wasn’t it better to lie to yourself for the sake of serenely living out the time you have left? As the girl had tried to make me understand, maybe this is why most people refuse to take this step: once you do, there is no turning back, and you must accept the consequences.

Lost in my own thoughts as I was, I didn’t realize that I had already made it to the entrance of the cemetery. Distraction wasn’t the only reason, though. The cemetery was hardly recognizable, as it was surrounded by scaffolding, crush barriers, and signs warning away trespassers. By the looks of it, the construction site must have been there for quite some time already; it certainly hadn’t been hastily pieced together that morning. I looked around for a while, confused and stupefied. There was no doubt that I was in the right place; I recognized the very same gate through which I had literally fled the night before, but it was closed and locked, and it bore a sign stating that it had been under renovation since two weeks ago. Dumbfounded, I explored the entire perimeter of the cemetery, but the sign was clearly correct. There was even a notice on the church saying that functions wouldn’t take place for a few weeks, and they had been suspended for a while already.

I was sure then that there had been no funeral the day before. Nor had I actually met that girl, apparently. I couldn’t have even set foot in that cemetery in the previous two weeks.

I stood there where I was, looking at the cemetery speechless, almost dazed, wondering if I had gone mad. After a few moments, I began walking away, heading home again, trying to no avail to find an explanation for the events of the previous day—assuming they had even happened.

Once I was home again, the dishes near the sink caught my attention once more. I thought again about the mug that I didn’t remember washing. Maybe I hadn’t washed it; maybe I didn’t drink that chocolate Saturday night, and maybe I dined at home, neglecting to do dishes. Maybe there had been no cloudburst. If that were the case, then the whole encounter and the rest of the events of that night had all been dreams.

All the neighbors I spoke with confirmed that not a single drop of water had rained the day before; however, I wasn’t brave enough to ask my acquaintances whether they remembered spending the day with me. For days, I kept wondering what had actually happened until I gave up and accepted that the entire experience must have existed only in my mind. Probably, I reasoned, unconscious thoughts had been bubbling up for a while and had finally burst out, making that surreal experience come to life as some kind of a dream. I cannot tell for certain whether I had this dream Saturday night or I had had some sort of hallucination; I can’t explain the extreme realism of the experience, and the only way to explain the amnesia would involve me sleeping through all of Saturday. I spoke to a psychotherapist some weeks later, and although I didn’t tell him everything about my experience, he said that I was sound of mind. I hope that’s true.

Despite my conviction that the girl was a dream or a hallucination, for months, I kept hoping to bump into her again, though in vain. More than once, I was sure that I had spotted her among the crowd, or recognized her as a passerby, barely avoiding making a fool of myself nearly every time.

It’s been months now. I have given up and accepted that the girl doesn’t really exist and that I will never see her again. Maybe I will dream about her, but I haven’t been so lucky thus far. In any case, that girl has profoundly changed me. Now that death herself has come and spoken to me to her own detriment, I won’t be able to look at her as I used to anymore—or rather, as I thought I did. Luckily, my anxiety has been mitigated somewhat, mostly turning into a desire to find a way out of this vicious circle that has cost and still costs millions of people their lives. Unfortunately, at the moment, I don’t even know if this is at all plausible.

The girl will hardly be able to give me any of the answers I need, so I will have to look for them elsewhere. I am afraid that many people would think my point of view on death is presumptuous at best and that they would hardly take me seriously.

However, somewhere in the world, there might be someone else to whom she has spoken like she did to me.

Now a life extension advocate at the beginning of his journey, he finds himself in a tough spot. We don’t know if, in his fictional world, science has begun realizing as it did in ours that aging is amenable to medical intervention, nor do we know if versions of LEAF and similar advocacy organizations exist there as well. Luckily for us, in our world, the situation is much clearer and it’s looking good; our understanding of aging is deep enough to envision interventions against it, and a very supportive community already exists. If you wish to join it, find out how here.

Nicola Bagalà is a bit of a jack of all trades—a holder of an M.Sc. degree in mathematics; an amateur programmer; a hobbyist at novel writing, piano and art; and, of course, a passionate life extensionist. After his interest in the science of undoing aging arose in 2011, he gradually shifted from quiet supporter to active advocate in 2015, first launching his advocacy blog Rejuvenaction before eventually joining LEAF. These years in the field sparked an interest in molecular biology, which he actively studies. Other subjects he loves to discuss to no end are cosmology, artificial intelligence, and many others—far too many for a currently normal lifespan, which is one of the reasons he’s into life extension.

Will Increased Lifespans Cause Overpopulation? – Article by Elena Milova and Steve Hill

Will Increased Lifespans Cause Overpopulation? – Article by Elena Milova and Steve Hill

Elena Milova
Steve Hill

Editor’s Note: The U.S. Transhumanist Party features this article by our guests Elena Milova and Steve Hill, originally published by the Life Extension Advocacy Foundation (LEAF) on October 30, 2016. In this article, both authors provide evidence that if aging was cured, then overpopulation would not be an issue. Not only is there a common trend among industrialized nations, in which, when the citizens become healthier, wealthier, and educated, they have fewer children, but there are also projections showing that global population growth is gradually falling and will come to a halt around the time the world’s population reaches 11 billion people.
***
~ Bobby Ridge, Assistant Editor, July 3, 2019

Any discussion of rejuvenation biotechnology almost certainly includes the subject of overpopulation and the objection that medical advances that directly address the various processes of aging will lead to an overpopulated world. Such dire predictions are a common theme in many discussions involving advances in medicine that could increase human lifespans.

Overpopulation is a word that gives the simple fact of population growth a negative connotation. It implies that an increase in the number of people will harm our lives in different ways, such as famine, scarcity of resources, excessive population density, increased risks of infectious diseases, and harm to the environment.

This concern, first raised by the work of 18th century reverend and scholar Thomas Malthus, has been a constant theme in both popular fiction and early foresights related to population growth. However, is it actually well-founded? We will be taking a deeper look at the historical and present population data and showing why overpopulation is unlikely to happen.

To get you started, this video with Bill Gates summarizes some of the key points about population and why a longer-lived and healthy society is good for keeping population growth in check.

What is the population, and how will it grow in the future?

Since the 1960s, both birth rate and population growth have been gradually falling. This will probably lead to a complete halt at 11 billion people near the year 2100. Here is a chart from the United Nations Population Prospects 2015 edition showing the corresponding projections [1].

Fig 1. Population of the world: estimates, 1950-2015, medium-variant projection and 80 and 95 percent prediction intervals, 2015-2100.

Here we can see the continuous, red trend line gradually leveling out into a straight horizontal line. However, before talking about why population growth is predicted to stop, let’s investigate why the population is even growing.

In order to ensure population growth, the number of children born per year must surpass the number of deaths in a given country. Typically, a fertility rate index equal to 2.1 is enough for the population to renew without growing in numbers, but a higher birth rate will lead to stable population growth.

In the illustrations below, you can see the global map of fertility and the projection of population growth by major regions [2]

Fig 2. World Population 2010-2100 United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Data Booklet. ST/ESA/SER.A/377.

Fig 3. Total fertility 2010-2015 United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Data Booklet. ST/ESA/SER.A/377.

The biggest contributors to the present level of population growth globally are India and several African regions, while many countries (especially in Europe) face depopulation because of their low birth rate. In the future, most of the population growth will be due to Africa.

Our intuition may tell us that it is unlikely that the least developed countries would be producing most of the population; after all, the standards of living in developed countries make for better conditions to have more children.

However, in reality, there are many factors that can lead to a decline in birth rate during the transition to a developed country: education (access to education for women typically postpones marriage and childbirth), unemployment (families try to control their family size to use fewer resources), and access to contraceptive techniques and cultural norms of using them, to name just a few [3].

Economic development is known to affect the time of birth; for example, recession encourages childbirth later in life [4]. National policies to combine work and family life also represent an important factor that may affect fertility rate in both directions. Globalization will “deepen” (in a world-systems theory sense) the less technologically advanced countries, making it very likely that the “higher birth rate” issue in these countries will also decline.

There is supporting evidence showing that moving to an advanced, industrialized economy changes the birth rate of immigrants. The fertility rates of immigrants to the US have been found to decrease sharply in the second generation [5]. Other studies demonstrate that the presence of immigrants does not compensate for declining birth rates [6].

Fig 4. Declining birth rate leads to gradual slow down of the population growth. The chart shows a UN projection in population size change in percent until 2100 for major regions[7].

The relationship between the level of the development of a country and fertility can be seen in the next chart. It is worth noting that when the Human Development Index (HDI) becomes higher than 0.85, country development starts promoting the birth rate again [8]. However, this kind of situation is very rare, historically, and therefore not significant enough to shape global population projections.

Fig 5.  Fertility vs HDI Index. Data source: United Nations Human Development Index (HDI), UN – Population Division (Fertility), 2015 Revision, Gapminder. Source: OurWorldInData.org/fertility/.

Thus, the least developed countries are more likely to have higher birth rates because people there have no reason to postpone childbirth, nor are measures for contraception widely accessible. The only factor holding back population growth in these regions may be the high level of child mortality and overall mortality due to infectious diseases and undernourishment.

With sustainable development goals focused on the solution of both problems, Africa has the potential to become the biggest human factory in our history. However, taking into account how fast fertility rates can fall because of the adoption of new technologies, this is far from certain.

Fig 6.  How long did it take for fertility to fall from more than 6 children per woman to fewer than 3 children per woman?  Data source: The data on the total fertility rate is taken from the Gapminder fertility dataset (version 6)  and the World Bank World Development Indicators. Source: OurWorldInData.org.

But won’t we run out of space?

In all projected future scenarios for Africa, its population will continue to grow. Today, there are 7.4 billion people on Earth. We are used to thinking that this is already too much, but is that true? First of all, let’s see how much space on Earth we humans actually take up. In 2012, the team of the project “Per Square Mile” led by Tim de Chant produced an infographic showing how big a city would have to be to house the world’s 7 billion people.

The city limits change drastically depending on which real city is used as the model and what its population density is, but this still gives us an idea of how much of our beautiful planet is really inhabited and how much spare space we still have.

If the projection of population growth by the United Nations is correct, in the next 84 years, there will be about 11 billion people. This means that if all of humanity were concentrated in a land area with a population density similar to New York, it would at most occupy the size of 3 US states by 2100.

2012                                                         2100

Fig 7.  7 bln city with population density of New York/11 bln city with the same population density. From the “Per Square Mile” project by Tim de Chant. Note: the picture at right is modified by the article authors to illustrate the potential growth. The state of Texas is about 700,000 square kilometers, which corresponds to about 7 billion people. The states of Texas, New Mexico (about 315,000 km^2), and Louisiana (about 135,000 km^2) combined represent 1,150,000 square kilometers, which corresponds to about 11.5 billion people by 2100.

Does this mean that population growth is not an issue? From the point of view of the space we humans need, likely so. However, our species’ survival is dependent on many other factors, such as the environment necessary to produce our food and other goods.

Are we going to run out of food?

We should admit that it is about fifty years too late to be concerned about extensive population growth and its consequences, such as famine, because the highest birth rate and population growth was observed from the 1960s to the 1980s. Our population grew by one billion people in just 14 years (going from 3 to 4 billion); however, no big societal or economic challenges were encountered.

Moreover, the next two billion increases in population appeared in 13 and 12 years, respectively [9], but once again, no famine caused by the deficiency of global food production followed [10]. The famines of the second half of the 20th century were provoked by how the food was distributed. Factors such as administrative incompetence of local governments, wars and natural disasters happening several years in a row played the greatest role in creating famine during this period.

Today, global society is taking measures to eradicate hunger worldwide by 2030. This is very likely to be the case, as the number of people suffering from hunger is decreasing fast. In 2012, it was one in eight, while in 2015, it was already one in nine, which corresponds to 795 million people. Below, you can see the Hunger Map by the World Food Program illustrating the progress.

Fig 8. FAO, IFAD and WFP. 2015. The State of Food Insecurity in the World 2015. Meeting the 2015 international hunger targets: taking stock of uneven progress. Rome, FAO. Sources: www.fao.org/publications/sofi/en/ Undernourishment data: FAO Statistics Division (ESS) – www.fao.org/economic/ess

If we compare the food supply in 1965 and in 2007, we can clearly see that overeating is more of a global issue than undernourishment, as in most countries, the calorie intake has grown significantly. This could not have happened if our society was suffering from food underproduction, as the food would not be available to overeat, and problems such as obesity would not be so prevalent.

Fig 9.  Food supply 1965 vs 2007 Source: Gapminder statistics (www.gapminder.org/)

Astoundingly, this means that a population explosion has passed relatively unnoticed – all thanks to the “Green Revolution” (rapid development of new agriculture techniques, such as fertilizers, irrigation and selection). The concern that there will be a food shortage in the future neglects further technological advances such as aquaponics, hydroponics, aeroponics, vertical farming, 3D-printed housing, algae farms, and many other technologies that could provide enough food for all.

The need for more food production represents an excellent opportunity for entrepreneurs, so it is unlikely that the development process of new technologies would suddenly stop, especially taking into account the objective need for rapid changes due to environmental issues.

According to a report by the Food and Agriculture Organization of the United Nations, “Livestock’s long shadow”, in 2006, livestock represented the biggest of all anthropogenic (i.e., due to human activity and with potentially harmful side effects) land uses, taking up to 70% of all agricultural land and 30% of the ice-free terrestrial surface of the planet [11].

Scientists admit that while it is still possible to expand agricultural land in some countries in accordance with the increasing need for food, this expansion cannot go beyond the limits of the carrying capacity of our planet. The report states that livestock is responsible for about 18% of the global warming effect, 9% of total carbon dioxide emissions, 37% of methane and 65% of nitrous oxide. Water use for livestock represents about 8% of all human water use (7% of this being used for feed irrigation).

New technologies can provide solutions for the numerous environmental issues related to traditional farming. For instance, hydroponics offers around 11 times higher yields while requiring 10 times less water than conventional agriculture [12]. The energy needs of a hydroponic facility are much higher (up to 80 times more), but thanks to emerging clean renewable energy technologies, this increased demand may not be an issue [13].

Today, there are many companies engaged in the creation of lab-grown meat, such as Supermeat and Memphis Meats. Making a laboratory into a farm is beneficial in many ways, starting from less pollution and fewer greenhouse gas emissions (mostly caused by animal digestion processes).

Sterile conditions in the lab lead to decreased risk of infections and allow the exclusion of antibiotics from the process of meat production. Lab-grown meat can be designed to contain less fat or even fats and proteins with new characteristics (for instance, essential Omega fatty acids).

With less space necessary for laboratory meat production and no waste, it will be possible to ensure disseminated local production in order to cut transportation time and reduce the usage of preservatives. The same system can be used to grow fish meat as well, thus reducing the impact of fishing and fish-farming on the environment. It is interesting to note that not only meat but also other animal-derived products, such as leather, can be produced in a lab, like is done by Modern Meadow.

There are attempts to create new edible products that taste like meat but are completely without animal ingredients, such as Impossible Foods. The recently created vegan ‘Bloody Burger’ by Impossible Foods “uses 95% less land, 74% less water and emits 87% fewer greenhouse gas emissions than its cattle-derived counterpart”. By concentrating on the heme molecule, the mixture apparently “looks like meat, tastes like meat and sizzles like meat“.

These solutions are also great from an ethical point of view, as this technology can reduce animal suffering. The rate of transition to these new ways of animal product creation is widely dependent on political will and social support. It is important to note that there is also significant progress regarding access to drinking water. During the Millennium Development Goals period (1990-2015), it is estimated that, globally, use of improved drinking water sources rose from 76 per cent to 91 per cent. 2.6 billion people have gained access to an improved drinking water source since 1990.

The MDG target of 88 per cent was surpassed in 2010, and in 2015, 6.6 billion people used an improved drinking water source. There are now only three countries (all located in sub-Saharan Africa and Oceania) with less than 50 per cent coverage, compared with 23 in 1990 [14]. New technologies for cheap water desalination and water collection from the air are also helping to improve the situation.

If population growth is not exactly an issue, then what is?

What we really should be concerned about is the age structure of the population. Regardless of the level of technological development, its core are the people of working age who are producing goods, paying taxes, and supporting the non-working groups, such as children and the elderly – the latter needing the most resources because of the state of their health.

Due to population aging, the share of working-age people is shrinking while the share of people who are at least 60 years old is growing. Population structure change is the most evident in Europe and Northern America, while the “Global South” has not experienced it yet – but will experience it in the next few decades.

Fig 10. Percentage of population in broad age groups by major area in 2015. Source: United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Data Booklet. ST/ESA/SER.A/377

Soon, one third of the population worldwide is going to be aged sixty or over, which means more social protection and healthcare expenditures and more working age people involved in nursing the elderly. However, it would be wrong and unjust to see the elderly as a burden, while these people have contributed so much to the incredible progress that our society has made.

They have all the same human rights as everyone, including the right to life and right to health. As age-related health deterioration is the main reason why society has to provide so much support to the elderly, it would be only logical to see the development of rejuvenation biotechnologies as the way to improve the situation.

What would life be like if we introduced rejuvenation technologies globally?

Before the era of universal medicine, people who managed to reach their sixties were still in relatively good health. However, once the onset of age-related diseases began, they died very quickly.

Modern medicine has changed that by slowing down the development of age-related diseases, hence extending the period of productivity. The downside is that this has also extended the period of illness, because treatments to prevent age-related diseases are not yet introduced into universal clinical practice.

In the near future, new interventions to slow down the aging process will become accessible, and then a shift will occur: the period of youth and adulthood will be extended due to better health, and the period of illness will be significantly postponed. In their sixties, people will remain as strong and vital as 40-year-old people are today. Some leading scientists predict that this may also lead to maximum lifespan increases of up to 150 years or more.

This is, of course, hard to prove, because as with many other things in human history, it is a unique situation that has never happened before, but some studies have proposed how aging would look given these three scenarios [15].

Fig 11. A:Pre Universal Medicine, B: Current medicine, C: Slowing aging. Source: Blagosklonny, M. V. (2012). How to save Medicare: the anti-aging remedy. Aging (Albany NY), 4(8), 547-52.

Whilst it is too early to be overly optimistic, we still should mention that apart from these three scenarios, there is a fourth possibility called negligible senescence. Negligible senescence in nature happens when a species does not display signs of aging, regardless of the passage of time. A number of species exhibit negligible senescence, including the rougheye rockfish (Sebastes aleutianus).

The ocean quahog (Arctica islandica) and some kinds of turtles are also negligibly senescent, but they still die because the expansion of their shell ultimately limits their movement. More examples can be found here at the excellent HAGR (Human Ageing Genomic Resources) database.

At some point in time, medical technologies may become so sophisticated that they will be able to bring all of the processes of aging under medical control. If that is the case, then aging will always remain at a subclinical stage, because the repairs to our bodies will keep up the pace with damage accumulation, allowing people to look and feel young for an indefinite period of time.

Most likely, it will take decades for medical science to progress this far, but we should also admit that some of the technologies necessary for this transition already exist, e.g., stem cell therapies, early nanorobots, CRISPR and gene therapies, immunotherapies, senolytics, and geroprotectors (drugs that slow down the aging process).

How will increased lifespan affect population growth?

The possibility of significant life extension using medical interventions was not even considered by the academic community until recent years, so there were not many projections of how increased lifespans and negligible senescence would affect population growth. However, a few years ago, such a projection was done for Sweden.

One of the more realistic scenarios is one where only a small share of the population accepts negligible senescence technologies at the beginning (this could be due to a slow dissemination process, ethical or religious objections that people have to overcome, or a high cost of the new technology) with a gradual increase (1% added to the negligibly senescent group each year). It is assumed that some small share of the population will never accept these technologies and will age in the traditional way.

In this case, population change in Sweden will not lead to population growth but can, to some extent, mitigate the process of depopulation over 100 years of medical innovations [16].

Fig 12. Population projection for a scenario of growing acceptance of antiaging interventions. Projection of the Swedish population until year 2105, assuming the negligible senescence scenario for initially small proportion of population (10%), with growing acceptance rate over time. Life extension interventions start at age 60 years, with 30-year time delay from now.

This might be the likely scenario in most developed countries. Taking into account that new technologies tend to be expensive even for developed countries’ middle classes, the developing countries most possibly will reach the same level of implementation later in time, when their fertility rate will be already affected by the index of development. In this case, the fall of their population growth will be smaller due to decreased population mortality.

In a more optimistic scenario, where all the population has access to negligible senescence technologies and they are applied to everyone who is at least 60 years old, population growth in 70 years will be around 22%. The earlier the application, the bigger the population growth. If negligible senescence technologies are applied at the age of 40, then the estimated population growth will be nearly 47% in 70 years.

Fig 13. Projection of the Swedish population until the year 2105, assuming the negligible senescence scenario. Life extension interventions start at age 60 years, with a 30-year time delay from now.

There are three main conclusions we can make based on this data.

  1. The growing share of people using negligible senescence technologies could help optimize the balance between workforce and retirees, hence maintaining economic development. People who are at least 65 years old will be about one-third of the global population in 2100, so we are talking about 3-4 billion old people who could be healthy and productive or ill and frail, depending on which strategy that global society implements.
  2. Negligible senescence is a synonym of good health, which means that the burden of age-related diseases and their social consequences will be mostly eliminated.
  3. Population growth, surprisingly, will not be as dramatic as is often imagined, leaving a significant period of time for adaptation, adequate measures of population growth control, and new territories’ development.

Is mitigating aging not only a need but also a legal obligation?

Even if negligible senescence remains a long-term goal, the emerging technologies to address the various aging processes [17] represent a unique opportunity to maintain older people in good health, allowing them to enjoy healthier lives, remain active, learn new skills, and contribute to the development of society. We owe them our present well-being. Not only have these people contributed a lot to create the things we have now, including better nutrition, healthcare, and a comfortable and safe habitat, they have also worked hard to change traditions and wisdom and helped to carry the concept of equal human rights forwards. This is why it is especially poignant to understand that geroprotective technologies and their potential are being underestimated and that they are not receiving the level of social approval and support that they rightly deserve.

According to the World Health Organization (WHO) Constitution, the objective of the WHO is “the attainment by all peoples of the highest possible level of health”. It is worth noting that WHO defines health as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” [18]. While this definition may seem quite spacious, it was made this way purposefully to ensure that member states’ activities in improving the health of their people would never stop.

Conclusion

The need for constant improvement of health is now a universal consensus.

Aging represents the root cause of severe diseases, such as cancer, Alzheimer’s, stroke, Parkinson’s, heart disease, COPD, type 2 diabetes, osteoarthritis and atherosclerosis, leading to disability of the elderly and to a wide range of negative social consequences, which makes it the perfect target for the global healthcare system [19].

These diseases can only be cured if the actual aging processes are directly addressed and halted while the damage is repaired or reversed by medical interventions. Therefore, according to WHO and United Nations policy, this means that global society has an obligation to eventually cancel aging in order to achieve the highest possible level of health for all people.

Literature

  1. United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Volume II: Demographic Profiles (ST/ESA/SER.A/380).
  2. United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Data Booklet. ST/ESA/SER.A/377.
  3. Mather, M. (2012). Fact sheet: The decline in US fertility. Population Reference Bureau, World Population Data Sheet.
  4. Lanzieri, G. (2013). Towards a ‘baby recession’ in Europe?. Europe (in million), 16(16.655), 16-539.
  5. Nargund, G. (2009). Declining birth rate in Developed Countries: A radical policy re-think is required. FV & V in ObGyn, 1, 191-3.
  6. Camarota, S., & Ziegler, K. (2015). The Declining Fertility of Immigrants and Natives. Center for Immigration Studies.
  7. United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Key Findings and Advance Tables. ESA/P/WP.241.
  8. Myrskylä, M., Kohler, H. P., & Billari, F. C. (2009). Advances in development reverse fertility declines. Nature, 460(7256), 741-743.
  9. United Nations, Department of Economic and Social Affairs, Population Division (1999). The World At Six Billion. ESA/P/WP.154.
  10. Gráda, C. Ó. (2007). Making famine history. Journal of Economic Literature, 45(1), 5-38.
  11. FAO, U., & Steinfeld, H. (2006). Livestock’s long shadow: Environmental issues and options. Rome:[sn].
  12. Barbosa, G. L., Gadelha, F. D. A., Kublik, N., Proctor, A., Reichhelm, L., Weissinger, E., … & Halden, R. U. (2015). Comparison of land, water, and energy requirements of lettuce grown using hydroponic vs. conventional agricultural methods. International journal of environmental research and public health, 12(6), 6879-6891.
  13. REN21. 2016. Renewables 2016 Global Status Report (Paris: REN21 Secretariat).
  14. Unicef. (2015). Progress on Sanitation and Drinking-Water: 2015 Update and MDG Assessment. World Health Organization: Geneva, Switzerland.
  15. Blagosklonny, M. V. (2012). How to save Medicare: the anti-aging remedy. Aging (Albany NY), 4(8), 547-52.
  16. Gavrilov, L. A., & Gavrilova, N. S. (2010). Demographic consequences of defeating aging. Rejuvenation research, 13(2-3), 329-334.
  17. López-Otín, Carlos et al.(2013). Hallmarks of Aging. Cell , Volume 153 , Issue 6 , 1194 – 1217
  18. World Health Organization. (2014). Basic documents. World Health Organization.
  19. Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., … & Rando, T. A. (2014). Aging: a common driver of chronic diseases and a target for novel interventions. Cell, 159(4), 709.
Elena Milova: As a devoted advocate of rejuvenation technologies since 2013, Elena is providing the community with a systemic vision how aging is affecting our society. Her research interests include global and local policies on aging, demographic changes, public perception of the application of rejuvenation technologies to prevent age-related diseases and extend life, and related public concerns. Elena is a co-author of the book Aging prevention for all (in Russian, 2015) and the organizer of multiple educational events helping the general public adopt the idea of eventually bringing aging under medical control.
***
Steve Hill: Steve serves on the LEAF Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Steve Hill Interviews Sarah Constantin of The Longevity Research Institute

Steve Hill Interviews Sarah Constantin of The Longevity Research Institute

Sarah Constantin
Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by our allies at the Life Extension Advocacy Foundation (LEAF) on May 9th, 2018. In this article Mr. Hill interviews Dr. Sarah Constantin, a researcher with a focus on machine learning at The Longevity Research Institute. This is an excellent article, especially if you want to learn more of the hard science behind longevity research. The topics of the interview range from deep learning being applied to pharmacology, to optimal mouse strains, and ideal areas of research to target age-related diseases.

~Bobby Ridge, Assistant Editor, June 30, 2019

Today, we have an interview with the Longevity Research Institute, a new group that launched in April 2018. The goal of the Institute is to identify therapies that can demonstrably extend healthy human lifespan by 2030 at the latest.

Searching for longevity

There are dozens of compounds and therapies that have been demonstrated to increase the lifespan of mammals. Recently, there have been some impressive examples of rejuvenation in animals using a variety of approaches, including partial cellular reprogramming, stem cell therapy, and senescent cell removal. More importantly, in many of these studies, age-related diseases have been delayed or even reversed.

Unfortunately, very few of these studies have had independent follow-ups or replication, and that is slowing down progress. The Longevity Research Institute is aiming to bridge the gap between basic science and commercial drug development.

It has chosen the field of aging research as its area of focus for one simple reason: age-related diseases are the leading cause of death globally. Heart disease, stroke, cancer, diabetes, Parkinson’s, Alzheimer’s and many more diseases are all caused by the various processes of aging.

The data from hundreds of animal studies tell us that aging is not a one-way process and that the rate of aging is something we can slow down or even reverse. Experimental results show that we can increase the healthy lifespan of animals significantly and delay the onset of age-related diseases in doing so. If we could translate those findings to humans, we could potentially increase the healthy period of life, known as health span, or even increase our lifespan beyond current norms while remaining healthy.

The majority of aging research consists of basic science that focuses on the mechanisms of aging, studies involving invertebrates like worms or fruit flies, and experiments that examine the effect of therapies on biomarkers of aging. However, the Longevity Research Institute believes that the way to find effective treatments that could translate to humans is by testing interventions on mammals to see if they increase lifespan or if they delay or reverse symptoms of aging, such as frailty, cognitive decline, and the prevalence of age-related diseases. Robust mammalian lifespan studies are quite rare in aging research due to their long duration and thus cost; the Institute believes they are worth doing despite this challenge.

Its philosophy is to be skeptical of results that depend on too many uncertain assumptions, such as particular mechanisms of aging or analogies between invertebrate and human biology. It believes that the closest way to measure the health and lifespan of a human is to measure the same things in mammals.

Replicating and Extending Lifespan Results

The majority of studies that have been shown to increase lifespan are rarely independently replicated to confirm the findings. There are therapies that, decades later, still have had no follow-up, and the Longevity Research Institute would like to change this situation.

To that end, it will be engaged in grant writing to obtain funds so that researchers studying aging will be able to conduct lifespan studies in mice and rats. The Longevity Research Institute also plans to commission its own studies and contract research organizations to carry them out.

It has a long list of promising interventions and is considering becoming involved with carboxyfullerenes, epithalamin, and stem cell transplants, for example. It is also interested in testing combinations of therapies to see if they have synergistic effects.

As translational research on aging is really a new, uncharted territory, the Institute is working with the Interventions Testing Program and METRICS to design reproducible animal studies. As part of that process, it will be testing genetically heterogeneous animals and using blind, randomized studies to reduce bias. A blind experiment is an experiment in which information about the test is hidden from participants, to reduce or eliminate bias, until after a trial outcome is known.

Best practices and transparency

Establishing best practices and protocol for translational aging research is a top priority here, and its work could help set the stage for future translational efforts. If superbly designed research protocols can be designed and made accessible to everyone, then they could be a real help in standardizing aging research and ensuring that the quality of results is the best it can be.

As part of its commitment to transparency and knowledge sharing, a condition of funding projects is that all experimental data will be made freely available to the public, as will pre-registration of experimental designs. The Institute will further protect this open science initiative by using blockchain technology to make immutable, publicly accessible records of everything it does.

We had the opportunity to talk with Sarah Constantin, Ph.D. and one of the key figures at the Longevity Research Institute, about their work. Sarah is a data scientist specializing in machine learning.

Your group believes that we need to conduct lifespan studies in mice in order to confirm that something might translate. However, some researchers believe that using multiple biomarkers of aging allows them to project, within a reasonable margin of error, changes to potential lifespan. This is becoming more relevant as the accuracy of biomarkers, and the use of comprehensive biomarker panels, becomes more commonplace. How do you respond to this?

There’s some very interesting stuff going on with biomarkers of aging.  We’re able to predict mortality with AUCs of 0.8-0.9, which is quite good, with aging biomarkers, including things like blood panels of inflammatory and metabolic markers, DNA methylation, and phenotypic markers such as BMI and frailty. Some of these biomarkers are things we’re planning to measure in our animal studies, and they should give us interim results on whether the interventions we’re testing affect the predictors of aging. I still believe that we can be most confident in whether a treatment promotes longevity when we’ve tracked its effects throughout an organism’s lifespan. We do know of examples (such as calorie restriction in primates) in which it’s equivocal whether the treatment extends lifespan but it clearly improves age-related biomarkers, and you have to do a lifespan study to distinguish those cases.

Advances in deep learning and systems pharmacology are allowing us to project interactions and potential therapies far more efficiently than ever before. What are your thoughts on these approaches, and will you be looking to use them in your work?

The deep learning and systems pharmacology approaches are actually where I started in biotech; I did machine learning at Recursion Pharmaceuticals, which is taking those approaches for doing phenotypic screens for genetic disease treatments. I think they’re really useful for drug discovery, at the beginning of the pipeline, where they can enable you to search a wider space of drug candidates. At LRI, we’re starting all the way at the other end of the pipeline, with drugs that have already been tested and shown promise in vivo. However, once we make some progress on those, then yes, it could make sense to start doing some of these machine learning-enabled approaches.

What is the ideal mouse strain for aging research, particularly lifespan studies, in your view?

Well, the Interventions Testing Program at the National Institute of Aging is using three-way heterozygous mouse crosses, which I think is the ideal. A single inbred strain of mouse doesn’t have much genetic diversity, so often what you’re testing is the effect of a treatment on that particular strain of mouse, and the results won’t transfer to another strain.

The use of progeria mice is common in aging research due to the shorter study time, but these models are often criticized as not being representative of true aging; what are your thoughts on the prevalence of progeria mice in aging research, and are they a relevant model for what we are trying to achieve?

I think progeria mice are an imperfect proxy. There are a lot of different kinds of progeria, and they exhibit some but not all of the typical symptoms of natural aging.  I’d have more confidence in studies done on aged mice than progeric mice.

We see that you have a strong commitment to ensuring public access to scientific knowledge. What inspired you to make such a wonderful and strong commitment to open science?

Well, coming from a data science background, I’m hyper-aware of how easy it is to fool yourself with data.  You can massage anything into a spurious result if you test enough hypotheses and pick your subgroups artfully. Really, the best way to guard against that is to share the raw data so that people can run their own analyses. Making science more open is how you make it more trustworthy.

Is there a publically viewable list of the targets that you are interested in testing?

The list is still evolving, but some of the first things we’re looking into testing are carboxyfullerenes, which seem to have neuroprotective and life-extending effects, and epithalamin, which is a pineal gland-derived peptide that’s been reported to extend lifespan and even reduce human mortality. Both of these are sort of in the sweet spot of not being the subject of that much research to date, but what there is is very promising, so the value of information is high.

What is likely to be your first target for studies, and what is the rationale behind your choice?

I think people should know that there’s a lot of low-hanging fruit in aging research — treatments that we have reason to believe might work but that we’d still have to test. The misperceptions are either that life extension is so speculative that we’ll never get there or that we already know how to do it and you just have to take the right supplements to live forever. I think the reality is that we’ll have to do a lot of experimental work, but it’s highly possible that, in time, we might find something that extends healthy lifespan in humans.

We would like to thank Sarah for taking the time to do this interview with us, and we look forward to seeing her team’s progress in the near future.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Not Classing Aging as a Disease is Not a Major Problem – Article by Steve Hill

Not Classing Aging as a Disease is Not a Major Problem – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by at the Life Extension Advocacy Foundation (LEAF) on July 19, 2018. In this article, Mr. Hill does an excellent job explaining why the lack of the definition of aging as a disease under the FDA is not so bad as is sometimes feared. Personally, I do not agree with this. Relying on off-label use is not a good idea because that is much slower of a process than doctors quickly seeing that a drug has FDA approval. Once the FDA considers aging as a disease, pharmaceutical companies will quickly enter this arena and make increasingly better drugs. Mr. Hill makes some excellent points, though, and I highly recommend this article. 

~ Bobby Ridge, Assistant Editor, June 29, 2019

A common concern in the community is that the FDA, the EMA, and other bodies, such as WHO, do not classify aging as a disease and that this poses a problem for developing therapies that target aging. However, this is not really as serious an issue as some people would suggest; today, we will have a look at why that is.

Why this will not stop progress

Aging is a variety of distinct processes, damages, and errors; therefore, simply treating aging in clinical terms is not a viable endpoint. For a clinical trial to be conducted, it requires a verifiable indication, and aging is too general for the FDA and EMA to classify it as a disease.

It also is not a major challenge for damage repair-based approaches, such as those proposed by SENS and the Hallmarks of Aging, as these approaches are not focused on an all-in-one therapy with the indication of “aging”. They are based on a strategy of dividing damages into manageable groups and developing a suite of rejuvenation therapies that addresses each of them.

No single therapy will reverse or halt all of the aging processes when used alone, nor will it prevent all age-related diseases that accompany them. So, to have aging as an indication in any clinical trial would be pointless for any damage repair therapy.

Researchers are free to target aging processes

That said, researchers are very well aware that the processes of aging, which lead to the familiar diseases of aging, are a problem, and this is where the focus lies. There has been considerable effort to classify these processes and precursors of pathology as diseases themselves.

A prime example is the inclusion of sarcopenia (frailty and muscle loss) in the World Health Organization International Classification of Diseases (ICD) a few years ago thanks to lobbying by members of our community. Adding more general codes to the ICD that include these aging processes and precursors is an ideal solution, as it could potentially make it easier to organize trials and develop drugs that target the aging processes.

Back in June 2018, the World Health Organization released the new International Classification of Diseases (ICD-11). The previous version, ICD-10, was published in 1983, and the new ICD-11 will likely be the standard for years to come. The new ICD-11 now includes the extension code “Ageing-Related” (XT9T) for age-related diseases, and this should go a long way towards making focusing on aging easier for future drugs and therapies. Again, this is thanks to work by members of our community, who have spent countless hours researching and pushing for change.

Most aging hallmarks are very clearly linked to specific age-related diseases, such as beta-amyloid protein and malformed tau in Alzheimer’s, lysosomal aggregates in foam cells in atherosclerosis, and alpha-synuclein in Parkinson’s disease. Companies are perfectly welcome to target these aging processes directly, and indeed more and more researchers and big institutions are doing just that in order to treat age-related diseases.

Therefore, not classifying aging itself as a disease poses few barriers to developing therapies that address aging; it’s simply a case of working within the existing framework. UNITY Biotechnology is a prime example; this company is targeting senescent cells and applying its method to multiple age-related diseases; as everyone gets senescent cells, these therapies will be broadly applicable once they become available, and off-label use is likely to expand rapidly.

Also, rejuvenation therapies could, at first, be licensed as treatments for genetic disorders, even though the root cause of the pathology underlying those diseases is not aging. An example of this is the inherited mitochondrial disorders, known as mitochondriopathies, many of which are caused by mutations in the mitochondrial DNA (mtDNA). While these mutations are inherited and are not the result of age-related, deleterious damage to the mtDNA, the same repair-based approach can be applied: the allotopic expression of the protein in the nucleus, as proposed by MitoSENS, could potentially be used to repair the mtDNA allowing normal cellular function to resume.

The majority of damage repair therapies, if not all, could be developed as therapies for diseases with accepted indications and verifiable endpoints, which should satisfy bodies such as the FDA and EMA. Therefore, whether regulatory agencies perceive aging as a disease or not is of no consequence to the development of rejuvenation biotechnologies that address the aging processes.

This does not mean regulatory changes are not needed

Even though classifying aging as a disease is unnecessary, significant reform in the regulatory system is still needed in order to encourage investors and companies to put the time and money into researching and developing rejuvenation therapies.

One area in need of reform is the establishment of aging biomarkers, which indicate the repair or removal of age-related damage, as acceptable endpoints for rejuvenation therapies. Studies that use these biomarkers would also need to include long-term follow-up studies to ascertain the effects of a therapy over a longer period of time.

This would deviate from regulators’ normal requirements that therapies have to prove an effect on hard outcomes to be approved. In an ideal situation, patients should get rejuvenation therapies long before they are in immediate danger and once diseases have manifested, but this makes trials more time consuming and more costly to run.

However, back in February 2018, the FDA published a new guidance document detailing how early-stage Alzheimer’s patients might be identified, which, if accepted, would represent a significant change in policy and a step in the right direction. The document suggests that the results of imaging tests or suitable biomarkers could be enough to consider Stage 1 Alzheimer’s patients as suitable subjects for clinical trials.

This is a positive move as it means that therapies can be tested on people in the very early stages of Alzheimer’s rather than on those who have already suffered considerable if not irreparable damage to the brain, damage that no therapy could hope to address alone. This could mean that these early-stage patients could enroll in a clinical trial and take a therapy that could potentially prevent the disease from ever progressing further or reaching the point where cognitive decline begins.

In the case of repair-based therapies, it would then be a case of demonstrating that the early stages of Alzheimer’s disease were improved via the removal or repair of the underlying age-related damage, and suitable biomarkers would show this.

Moving with the times

Another area where regulatory bodies have struggled is keeping up with the rapid march of technology and medicine. Technologies such as gene therapies have struggled to gain traction due to an antiquated regulatory framework struggling to cope with them. Thankfully, this is also being acknowledged, and the regenerative medicine advanced therapies (RMAT) framework published earlier this year seeks to address this issue and make large-scale changes to how its regenerative medicine policy framework operates as a whole.

According to new FDA regulations, a drug is eligible for designation as an RMAT if:

  • The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and part 1271 of Title 21, Code of Federal Regulations;
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.

While the FDA created these new guidelines, we joined forces with the Niskanen Center to submit comments to the agency so that it would hear the voice of our community.

Conclusion

Aging not being classified as a disease by the FDA, EMA, etc. is not a major issue; the real need is for policy changes that make developing drugs and therapies that target the aging processes easier and more financially viable. It is good that changes are being made to current frameworks and that progress will almost certainly continue in these areas.

Meanwhile, we can continue to support the development of repair-based approaches to aging knowing that such therapies, if they work, will be approved even in the current regulatory landscape.

Steve Hill serves on the LEAF Board of Directors and is the Editor-in-Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.

Nicola Bagalà Interviews Reason of the Fight Aging! Blog and Repair Biotechnologies

Nicola Bagalà Interviews Reason of the Fight Aging! Blog and Repair Biotechnologies

Reason
Nicola Bagalà


Editor’s note: The U.S. Transhumanist Party features this article by our guest Nicola Bagalà, originally published by our allies at the Life Extension Advocacy Foundation (LEAF) on May 14th, 2018. In this article, Mr. Bagalà interviews Reason, an activist who has been helping scientists to cure age-related diseases and posting in-depth commentary on a blog dating back to the 2000s. Reason has helped multiple fundraisers and contributed much more to the progress of life-extension research. The topics of the interview range from a quick biography of Reason’s involvement in fighting age-related diseases, to a discussion of when aging will be defined as a disease by the FDA. The interview also covers Reason’s new company, called Repair Biotechnologies.

~Bobby Ridge, Assistant Editor, June 25, 2019

Most people interested in rejuvenation and life extension are familiar with Fight Aging!, one of the very first rejuvenation advocacy blogs dating back all the way to the early 2000s; if you’re one of them, then you certainly are familiar with Reason, the man behind FA!.

Over the years, Reason has been a patient yet relentless advocate, acting not only as an information provider for the public but also helping out innumerable organizations and companies in the field of rejuvenation biotechnology in financial and other ways. Back in the day when SRF didn’t exist yet, Reason was a volunteer for Methuselah Foundation; eventually, he helped fund companies such as Oisìn Biotechnologies, CellAge, and LysoCLEAR; and, earlier this month, Reason and Bill Cherman co-founded Repair Biotechnologies, a company focused on gene therapy for rejuvenation, as announced on FA!.

Bill Cherman is an investor in the rejuvenation community who, just like Reason, has contributed to development of many ventures in the field. He is a holder of a gold medal in the Brazilian Mathematics Olympiad, a BA in economics, and a candidate in the Master of Biotechnology Enterprise and Entrepreneurship program at Johns Hopkins. He founded Front Seat Capital, a venture capital firm looking to invest in startups with the potential to change the world.

Repair Biotechnologies, which is presently looking for a Chief Science Officer, will kickstart its activities with a project on thymic regeneration in partnership with Ichor Therapeutics—the creators of LysoCLEAR, Antoxerene, and RecombiPure. The goal of the company, as you can imagine, is to shorten the journey of rejuvenation therapies from the lab to the clinic.

It is extremely heartening to see more and more rejuvenation-focused companies and organizations sprouting and building up to the turning point when this emerging field of science will cease being fringe and become a hot topic not only in the relatively small circle of biogerontology (where it has been one for a while now) but also in business and public discourse. We’re very grateful to Reason and Bill for taking us yet another step closer to the finish line and for answering our questions.

We’d like to ask some details of your story as a rejuvenation advocate. When and under what circumstances did it become clear to you that aging is a problem?

While it would be delightful to claim that I am a rational entity who came to that conclusion through utilitarian thought, in fact, it was more of a bolt from the blue. For no apparent reason, it suddenly came to me one evening that I didn’t want to die – and not in the academic way that most people hold that conviction but a deep, visceral, adrenaline-laden realization of the sort in which one accepts immediately that something important in life has been done and determined, a corner turned. Before that happened, I was no more than passingly interested in aging as a topic, but afterwards… well, I woke up. Of course, that was a long time ago now, far prior to my present understanding of what is plausible and possible, and realization on its own achieves nothing. It took years to learn enough to progress any sort of understanding as to how a non-life-scientist could make a difference.

We have noticed that there has been a sea change in both progress and enthusiasm from the academic community for rejuvenation biotechnology and targeting aging directly to prevent age-related diseases. Have you observed a similar rise in support, and what factors, if any, do you think are driving this?

I think that these things progress in cycles, based on the timescale of human collaboration. It takes a few years to go from desire to setting up an organization, a few years for the organization to get somewhere, and a few years for others to be inspired to their ventures by the organization. Bootstrapping only looks smooth in hindsight. We have been transitioning from one business cycle to another these past few years, which looks like a big leap in enthusiasm as it occurs, but the roots of this were set down five to ten years ago. I would say those roots included the final tipping point studies for senolytics, the spin-off of the SENS Research Foundation from the Methuselah Foundation, the injection of funding for SENS around then, and a number of other, related items.

It we look around today, a bigger community is planting a larger crop of seeds that will come to fruition in the mid-2020s, and today’s seeds include startup biotechnology companies in the SENS space, new advocacy initiatives like LEAF hitting their stride, and so forth.

Thanks to the efforts of many advocates, yours included, public perception of rejuvenation is also shifting. How close do you think we are to widespread acceptance?

I don’t think acceptance matters – that might be the wrong term to focus on here. Acceptance will occur when the therapies are in the clinic. People will use them, and everyone will conveniently forget all the objections voiced. The most important thing is not acceptance but rather material support for development of therapies. The help of only a tiny fraction of the population is needed to fund the necessary research to a point of self-sustained development, and that is the important thing. Create beneficial change, and people will accept it. Yet, you cannot just go and ask a few people. Persuading many people is necessary because that is the path to obtaining the material support of the necessary few: people do not donate their time and funds to unpopular or unknown causes; rather, they tend to follow their social groups.

Last year, you talked about the importance of sustained advocacy being as important as supporting the research itself. You wrote about a number of approaches to advocacy, including ours. Have you noticed an improvement in the quality of advocacy since then, and do you still maintain that professional advocacy is as important to the cause as research is?

Fishing for compliments? I’m very pleased with the progression of LEAF and with advocacy in general in our space. People have come and gone over the years, but this latest group of advocates appears to have set up shop for the long term. That is important and a welcome change. I can’t keep writing Fight Aging! forever, if only because hands and schedules eventually give way under the accumulated burdens of the years. There must be far more voices doing this same sort of work, all in their own varied ways. Diversity and redundancy are both important aspects of advocacy – many people arguing in their own ways for a given point of view are needed in order to persuade the world at large.

Presently, rejuvenation is a relatively unknown topic; people who say they’re against this technology probably don’t think it’s a concrete possibility anyway. However, as more important milestones will be reached—for example, robust mouse rejuvenation—this might change. Do you think that these milestones will result in opponents changing their attitudes or becoming more entrenched?

Opposition to human rejuvenation therapies is almost entirely irrational; either (a) it’s a dismissal of an unfamiliar topic based on the heuristic that 95% of unfamiliar topics turn out to be not worth the effort when investigated further, or (b) it’s a rejection of anything that might result in sizable change in personal opinion, life, and plans, such as the acceptance of aging and death that people have struggled to attain. This sort of opposition isn’t based on an engagement with facts, so I think a sizable proportion of these folk will keep on being irrational in the face of just any scientific advance or other new factual presentation short of their physicians prescribing rejuvenation therapies to treat one or more of their current symptoms of aging.

On the other hand, there will be steady progress in winning people over in the sense of supporting rejuvenation in the same sense as supporting cancer research: they know nothing much about the details, but they know that near everyone supports cancer research, and cancer is generally agreed to be a bad thing, so they go along. Achieving this change is a bootstrapping progress of persuading opinion makers and broadcasters, people who are nodes in the network of society. Here, milestones and facts are much more helpful.

After years of financially supporting other rejuvenation startups, you’re now launching your own company focused on gene therapies relevant to rejuvenation. What drove your decision to do this?

In the course of funding companies, one learns a great deal about the bounds of what might be achieved and the sort of work that is needed: it isn’t uncommon for investors to become entrepreneurs and vice versa. There are large overlaps in the mental toolkits required, and it is a logical evolution seen from either side. Moreover, in the course of investing in startups, one meets people in the community, such as my cofounder Bill, who intend to both fund and run companies, and it turns out that we work together quite well. As in all such things, it has a lot more to do with happenstance leading to the right arrangements of people and much less to do with the technical landscape at the time.

Your company’s first objective is thymic regeneration. Why do you think the thymus is the ideal initial target for your work?

It is a very straightforward goal, with a lot of supporting evidence from the past few decades of research. It think it is important to set forth at the outset with something simple, direct, and focused, insofar as any biotechnology project can be said to have those attributes. This is a part of the SENS rejuvenation research agenda in the sense of cell atrophy: the core problem is loss of active thymic tissue, which leads to loss of T cell production and, consequently, immunodeficiency. However, the immune system is so core to the health of the individual that any form of restoration can beneficially affect a great many other systems. The many facets of the immune system don’t just kill off invading pathogens; they are also responsible for destroying problem cells (cancers, senescent cells), and they participate in tissue maintenance and function in many ways.

You are using gene therapy; why have you chosen this delivery method specifically and not, for example, a small-molecule approach?

If your aim is to raise or lower expression of a specific protein, and you don’t already have a small molecule that does pretty much what you want it to do without horrible side-effects, then you can pay $1-2M for a shot at finding a starting point in the standard drug discovery databases. That frequently doesn’t work, the odds of success are essentially unknown for any specific case, and the starting point then needs to be refined at further cost and odds of failure. This is, for example, the major sticking point for anyone wanting to build a small-molecule glucosepane breaker – the price of even starting to roll the dice is high, much larger than the funding any usual startup crew can obtain.

On the other hand, assuming you are working with a cell population that can be transduced by a gene therapy to a large enough degree to produce material effects, then $1-2M will fairly reliably get you all the way from the stage of two people in a room with an idea to the stage of having animal data sufficient enough to start the FDA approval process.

You are working with SRF spin-off company Ichor Therapeutics; what was the reason for choosing to work with Kelsey and the Ichor team?

Because they are great. Kelsey has achieved considerable success, bootstrapping from nothing but a plan, and has an excellent team. Their philosophy of development dovetails well with ours, both in terms of short-term development of a biotech startup and in the longer term of how we’d like to see this industry develop over the next 10-15 years.

Will your company focus on lab work, or do you plan to run human trials once a sufficiently advanced stage has been reached?

We’re absolutely signed up for the end-to-end path of getting a therapy into the clinic. That is the whole point of the exercise – to bring therapies into general availability. Of course, there will be a great deal of lab work to accomplish between here and there.

The FDA doesn’t recognize aging as a disease, so it won’t approve drugs to target it directly. Is this a problem for your company’s activities?

Remember that when talking to the FDA, one usually starts with just a small patient group with a single age-related condition, a fraction of everyone that might eventually be helped. This is done to control costs and ensure the best possible chance of a successful approval by narrowing the focus to a very clear, simple experiment. After this, one expands to larger patient groups and more expensive trials. As it happens, the effects of immunosenescence on health are so widespread and similar from individual to individual that it wouldn’t be hard to pick a clearly defined condition and patient population that covers near everyone in late life. Unfortunately, one would have to have very deep pockets indeed to pick that as the first option for entering the approval process – one has to work up to it.

What are Repair Biotechnologies’ possible future targets after thymic regeneration?

We’re looking into a couple of interesting options, guided by the SENS philosophy of damage repair, but it is very challenging to say at this stage which of them will prove the most advantageous to attempt. Obviously, at this stage, the primary focus has to be on success in our first venture.

What do you think are currently the most promising research avenues within each rejuvenation therapy subfield?

We have a challenge today in that we have the DNA of a patient advocacy community trying to get work to proceed at all. So, for fifteen years, our measure of success was “are people paying more attention to this?” Now, we have to start thinking like a development community, in which success revolves around “does this implementation actually work in humans, and how well does it work, and how much does it cost?”

In all too many cases, we don’t yet know the answers to these questions: the data isn’t there yet for senolytics, for example. So, you can look at senolytic efforts and know who has the most funding and attention but have no idea which of the therapeutic approaches actually represent the most significant progress at the end of the day. For all we know, dasatinib might turn out to be the most cost-effective of all of the current small-molecule approaches, with everything everyone has done since then coming in a poor second-best, and we won’t find this out for years, as no one has any incentive to run the necessary large-scale trials on an existing drug.

Dr. de Grey is hopeful, but not certain, that immunotherapy might make OncoSENS unnecessary. What do you think?

I have long thought that canonical OncoSENS – whole-body interdiction of lengthening of telomeres – might be rendered unnecessary by sufficiently advanced incremental progress in other areas of cancer research. That said, it should be so cost-effective that it is hard to imagine “sufficiently advanced incremental progress” not incorporating interference with telomeres in some way. People other than SENS-funded groups are working on it, after all.

If you think about it, restoring the immune system to youthful capacity should also help to achieve this goal; there is evidence to suggest that age-related immune dysfunction drives age-related cancer risk and that this correlates well with thymic decline. The world will still need highly effective, low-side-effect cancer therapies even if everyone has the cancer risk profile of a young adult, of course, but far less frequently.

What do you realistically expect might happen, over the next 25 years, in terms of rejuvenation research results, funding, clinical applications, and availability?

Well, that’s an essay in and of itself. I think my views on the technology itself are fairly widely known: I’ve written a few short essays on likely ordering of development. The funding will  continue to grow year-over-year to the degree that any success is achieved in the clinic. However, everything takes a very long time in medicine due to the way in which regulation works, no matter how fast the technology is running in the labs, and the pace of technological progress in biotechnology is accelerating. At some point, the system exemplified by the FDA will break because cheap and effective therapies coming out of the labs will be so far ahead of what is available in the clinic that they will leak out into some other form of commercial development. Who knows what that will look like? Perhaps it will be a network of overseas non-profits that run their own, lighter and faster, validations of trials and presentations of human data gathered from participating clinics. I think that next-generation gene therapies, evolutions of CRISPR, will likely precipitate this sort of reordering of the landscape.

Do you expect that aging might relatively soon be officially considered a disease, or a co-morbid syndrome, by WHO and the FDA?

No. Regulation typically lags behind reality by many years. What will probably take place is some sort of battle of wills and lawyers over widespread off-label use for rejuvenation therapies, most likely senolytics, that have only been narrowly approved for specific age-related conditions. That will go on for a while and, ultimately, generate sufficient critical press attention to induce regulators to back off from trying to suppress that off-label use and, instead, accept aging as an approved indication. This hypothetical scenario could run a decade or more from beginning to end.

The availability of rejuvenation therapies doesn’t depend only on their cost; it also depends on how they’re regulated in each specific country. Do you imagine “rejuvenation tourism” will exist for long, or at all, before these treatments are part of the standard medical toolkit everywhere?

The development of stem cell therapies is the example to look at here. These therapies were available via medical tourism for a decade prior to the first approved treatments in the US, and this continues to be the case even afterwards, as only a narrow slice of therapies have been approved. Medical regulation is slow-moving, and so medical tourism will be long-lasting. I think this will work exactly the same way for other broad classes of therapy, such as gene therapies.

What is, in your view, the biggest bottleneck to progress in aging research?

Either (a) the lack of funding for research and early-stage startup development or (b) the low number of entrepreneurs, one of the two. Probably funding, as money can be used to craft an 80/20 solution to the shortage of entrepreneurs, but entrepreneurs can only reliably solve the lack of funding problem if there are a lot of them. Almost every specific instance of things not moving forward that I’ve seen could be addressed by a well-thought-out application of funds to the situation.

The chasm between academic research and early-stage commercial development is also a sizable issue. The academic side does a terrible job of reaching out to find entrepreneurs and companies that can carry forward their research to benefit patients. The entire biotechnology industry (entrepreneurs, investors, bigger companies and funding entities) collectively does a terrible job of reaching back into the academic community to fund, encourage, and adopt the most promising research. So, projects that should move instead languish for years because no one is taking the obvious steps to improve on the situation.

Right now, there don’t seem to be any unexpected problems with the science that might jeopardize the development of rejuvenation. Do you think that any particular areas of research might run into difficulties down the road?

No. I think all the unexpected problems will be implementation details. It is perfectly possible to have the correct strategy and the wrong tactics, and this happens all the time in complex fields such as biotechnology – it doesn’t take much of an error in interpreting research results to derail the original plan and require a new direction. Most such challenges are short-term and can be worked around with some loss of time and money, but there are certainly past instances in which the company is lost because there is no viable way to salvage a better path.

This is what happened to one of the early AGE-breaker efforts, the development of ALT-711: removing AGEs still seems very much a correct approach to the age-related stiffening of tissues, but a drug that works in rodents will do nothing in people because the physiologically relevant AGEs are completely different. At that time, the researchers didn’t have that critical piece of information. We will no doubt see similar stories occur again in the future.

Caloric restriction and exercise may also potentially convey some small increase in life expectancy. Given that the goal is to reach longevity escape velocity, do you practice a particular diet or exercise program, and would you encourage people to consider such approaches?

I have always suggested that people look into the simple, reliable things they can do for better health. The way to look at this is through the lens of cost-effectiveness. Calorie restriction and exercise are cheap, easy, and highly reliable. They don’t adjust your life expectancy by decades, but since they are cheap, easy, and reliable, you should still look into it. There are many different ways to approach both, so just because an attempt fails or isn’t palatable, that’s no excuse to give up on the whole endeavor. At the end of the day, it is a personal choice, of course. We can always choose to be less healthy; that’s easy to do in the present environment.

You’ve written many articles on the topic of self-experimentation on FA. Can you summarize your views?

The current self-experimentation community – and here I include many disparate groups, only tenuously linked, with interests in nootropics, anti-aging, muscle building, and so forth – is woefully disorganized and ill-educated when it comes to the risks and scientific knowledge of the compounds they try. If one in twenty of the people who have tried dasatinib as a senolytic have (a) read the papers on pharmacokinetics in human volunteers, (b) recalculated likely human doses from the senolytic animal studies and compared them with human chemotherapy studies, or (c) actually tested the compound delivered by a supplier to ensure purity, I would be astoundingly surprised.

The bar for quality and safety in this community needs to be raised, and that is the primary purpose behind my writing articles on self-experimentation. Whatever I say, people are going to be out there trying senolytics – many of these compounds are cheap, easily available, and hyped. What they should be doing instead of rushing in is thinking for themselves and reading widely. If I can do a little to help make that happen, then all to the good.

What is your take-home message for our readers?

There is always a way to help accelerate the development of rejuvenation therapies – there is always something that one can do and feel good enough about doing to do it well. Don’t know what that something might be? Then talk with people in the community. Reach out, go to meetings, post online. Don’t force it. It will come to you in time.

Nicola Bagalà is a bit of a jack of all trades—a holder of an M.Sc. degree in mathematics; an amateur programmer; a hobbyist at novel writing, piano, and art; and, of course, a passionate life extensionist. After his interest in the science of undoing aging arose in 2011, he gradually shifted from quiet supporter to active advocate in 2015, first launching his advocacy blog Rejuvenaction before eventually joining LEAF. These years in the field sparked an interest in molecular biology, which he actively studies. Other subjects he loves to discuss to no end are cosmology, artificial intelligence, and many others—far too many for a currently normal lifespan, which is one of the reasons he’s into life extension.

A Poor Diet May Lead to Dysbiosis and Age-Related Diseases – Article by Steve Hill

A Poor Diet May Lead to Dysbiosis and Age-Related Diseases – Article by Steve Hill

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by the Life Extension Advocacy Foundation (LEAF) on May 27, 2019. This article reminds us of the strong connection between our gut microbiome and ageing, along with a review of a study that provides greater insight into the mechanism of how a poor diet can contribute to age-related diseases.

~ Bobby Ridge, Assistant Editor, June 21, 2019

The role that the gut microbiome plays in aging is increasingly being appreciated in the research world as more evidence arrives to support it. A new publication reviews the various supporting evidence and takes a look at the gut microbiome in the context of poor diets and how they may facilitate the progression of dysbiosis and disease [1].

What is the microbiome?

The microbiome is the varied community of bacteria, archaea, eukarya, and viruses that inhabit our guts. The four bacterial phyla of Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria comprise 98% of the intestinal microbiome.

The microbiome is a complex ecosystem whose activity regulates multiple functions of the gut and also interacts and helps to regulate our immune systems and energy metabolisms. The beneficial bacteria in our guts also help to prevent the growth of harmful bacteria, protect us from invasive microorganisms, and help to maintain the integrity of the intestinal barrier.

As we age, the diversity and numbers of beneficial bacteria tend to decline. There is a strong correlation between decreased microbiome diversity and declining health, and microbiome health has been associated with a number of metabolic conditions, such as type 2 diabetes and obesity. On the other hand, older people who maintain a more healthy gut microbiome tend to live longer and in better health.

We have talked about the role that dysbiosis, the age-related changes to the gut microbiome, plays in the loss of intestinal barrier integrity, which allows bacteria to infiltrate deeper into the body. This is likely to contribute to inflammaging, the chronic, age-related inflammation that drives disease progression and harms tissue regeneration.

Age-related gut dysbiosis is a microbial imbalance in the gut that favors a shift towards proinflammatory microbes and a decline of beneficial microbes, such as those responsible for creating butyrate (and other beneficial short-chain fatty acids), a compound vital for creating the energy that colonocytes and other gut wall cells feed on. These changes lead to chronic inflammation and impair the intestinal barrier, causing it to leak, hence the common name for the condition being “leaky gut” [2].

Abstract

Inflammatory diseases, such as inflammatory bowel diseases, are dramatically increasing worldwide, but an understanding of the underlying factors is lacking. We here present an ecoevolutionary perspective on the emergence of inflammatory diseases. We propose that adaptation has led to fine-tuned host-microbe interactions, which are maintained by secreted host metabolites nourishing the associated microbes. A constant elevation of nutrients in the gut environment leads to an increased activity and changed functionality of the microbiota, thus severely disturbing host-microbe interactions and leading to dysbiosis and disease development. In the past, starvation and pathogen infections, causing diarrhea, were common incidences that reset the gut bacterial community to its “human-specific-baseline.” However, these natural clearing mechanisms have been virtually eradicated in developed countries, allowing a constant uncontrolled growth of bacteria. This leads to an increase of bacterial products that stimulate the immune system and ultimately might initiate inflammatory reactions.

Easily digestible, energy-dense, low-fiber-content foods harm the microbiome

It is known that a diet with easily digestible, energy-dense, low-fiber-content is harmful to health and leads to the formation of visceral fat, the type of fat tissue that is stored deeper than normal belly fat and that forms around your major organs, including the liver, pancreas, and kidneys. Visceral fat also contributes to chronic inflammation and hence to inflammaging, helping to speed up aging and disease progression.

It also appears to influence the gut microbiome and cause changes to the bacterial populations in the gut. The strength of this influence remains to be seen, but its effect on health via changes to the microbiome may be considerable and equally as important as physical activity for health and aging.

Conclusion

This adds yet more fuel to the fire, making it increasingly clear that microbiome health and exercise are the foundations of longer, healthier lives and that we should do all we can now to ensure we achieve both things as part of a personal longevity strategy.

Science is progressing rapidly, especially in the aging field, but this is no reason to be complacent. Science, especially medicine, is, by its nature, complex and can be unpredictable. We all hope that rejuvenation therapies will arrive sooner rather than later, but it is hard to predict when they will be available; this could be in a decade, or it could be longer than we think. For that reason, we should do all we can now to increase our odds of making the cut.

Exercise and balanced diets are relatively low-tech and low-cost approaches to healthy longevity, and everyone in the community should be engaging in these practices if they are serious about living long enough to benefit from the arrival of more robust rejuvenation therapies.

Literature

[1] Lachnit, T., Bosch, T. C., & Deines, P. (2019). Exposure of the Host-Associated Microbiome to Nutrient-Rich Conditions May Lead to Dysbiosis and Disease Development—an Evolutionary Perspective. mBio, 10(3), e00355-19.

[2] Cullender TC, Chassaing B, Janzon A, et al. Innate and adaptiveimmunity interact to quench microbiome flagellar motility in the gut. Cell Host Microbe 2013; 14: 571–81.

Steve Hill serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ Magazine, Psychology Today, Singularity Weblog, Standpoint Magazine,  Keep Me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.