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The Best of the SENS AMA – Article by Steve Hill and Aubrey de Grey

The Best of the SENS AMA – Article by Steve Hill and Aubrey de Grey

Steve Hill

Dr. Aubrey de Grey


Editor’s Note: In this article, Steve Hill highlights the Ask Me Anything on Reddit held on December 7th by Dr. Aubrey de Grey.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, December 13, 2017

 

Dr. Aubrey de Grey from the SENS Research Foundation (SRF) did an Ask Me Anything on Reddit on December 7th, and there were many great questions and answers; we thought it would be a great time to summarize some of the best ones and offer a little commentary.

What do you think were the biggest wins of the last couple of years in SENS-relevant advocacy, research, and development? What has moved the needle?

There have been lots. On the research, I would highlight our paper in Science two years ago, which shows how to synthesize glucosepane, and our paper in Nucleic Acids Research one year ago, which shows simultaneous allotopic expression of two of the 13 mitochondrial genes. Both of those projects have been greatly accelerated in the meantime as a result of those key enabling breakthroughs; watch this space.

On advocacy, I think the main win has been the arrival of private capital; I would especially highlight Jim Mellon and his Juvenescence initiative because he is not only a successful, energetic and visionary investor, he is also a highly vocal giver of investment advice.

We are pleased to have been involved with the second project mentioned here, as we hosted the MitoSENS project at Lifespan.io, where it raised 153% of its initial fundraising goal. Less than a year later, after raising this money, it went on to publish the groundbreaking study showing that backup copies of mitochondrial genes could indeed be created in the nucleus. Dr. de Grey originally proposed the idea over a decade ago amid much scepticism; it is really good to see that years later he has been vindicated. This is the power of crowdfunding and how we as a community can make big changes in science by working together.

How do you feel about the impact of groups like LEAF advocating and reporting on rejuvenation biotech? Has the advocacy and reporting of these groups made your life any easier?

Massively! A huge thing that I say all the time is that advocacy absolutely relies upon the diversity of its messengers. Different people listen to different forms of words, different styles of messaging, etc. The more, the better.

It’s good to know that our work is appreciated and helping. Working together as a community is essential for progress, so it was nice to see this question and response from someone we respect a great deal.

We have said many times before effective advocacy efforts are just as important as the research itself. Professional advocacy has the potential to increase public support and funding, paving the way for the arrival of rejuvenation biotechnology. In the past decade or so, advocacy has mostly been left to volunteers and people such as Dr. de Grey.

Popular causes attract celebrities, public support, funding and investment; if we want a revolution in medicine and how we treat aging, then we must popularize the movement. There has been a serious shortage of full-time and organized advocacy; therefore, we decided to create LEAF to support groups like the SRF, advocate to popularize the cause, and help to raise much-needed funds for research efforts. We are only able to do this thanks to the support of the community, and we are extremely grateful to our Lifespan Heroes for helping us to do the work we do.

Aside from funding, what do you consider to be a burden or delay for your type of research?

Nothing. Seriously, nothing at all. We have the plan, and we have the people. It’s all about enabling those people by giving them the resources to get on with the job.

Indeed, funding for research is one of the four major bottlenecks slowing down the development of therapies that address the aging processes. The more funding the field gets, the more projects can be launched, the sooner breakthroughs can potentially happen, and the greater the benefits will likely be for all of us.

Is there anything new you are able to say about the breaking of cross-links in the extracellular matrix?

Absolutely. Short story, we now have a bunch of glucosepane-breaking enzymes, and we are within a few months of spinning the work out into a startup.

A suspected cause of degenerative aging is the accumulation of sugary metabolic wastes known as advanced glycation end-products (AGEs). These are wastes that are, in some cases, hard for our metabolism to break down fast enough or even at all. Some types, such as glucosepane, can form cross-links, gumming together important proteins such as those making up the supporting extracellular matrix scaffold.

The properties of elastic tissues (skin and the blood vessel walls) derive from the particular structure of the extracellular matrix, and cross-links degrade that structure, preventing it from functioning correctly. AGEs’ presence contributes to blood vessel stiffening with age, and it is implicated in hypertension and diabetes.

That SRF now has candidate enzymes is very significant because it means that there are now potential ways to remove these crosslinks from our tissues. There are many types of crosslinks, and we already know of compounds and drugs that can break other kind of crosslinks; the major problem is glucosepane, as it lasts a very long time, and, so far, nothing is known to remove it. Given that other types of crosslinks can be removed, Dr. de Grey rightly thought that there must be ways to remove (cleave) glucosepane from tissues; now, it seems that we are a step closer to that potentially becoming a reality.

If the SRF is successful in finding ways to break glucosepane crosslinks, this has huge implications for diabetes, hypertension and aging. It is great to hear that the organization is now reaching the point at which it is almost time to develop this as a therapy by creating a startup company.

It seems likely that artificial intelligence will be a necessary tool in order to reach longevity escape velocity. I was wondering how much of a role does artificial intelligence play in your research? Is this something you devote many resources to?

We don’t, but that is because other major players in this field (and good friends of mine), such as Alex Zhavoronkov and Kristen Fortney, are doing it so well already (with Insilico Med and BioAge, respectively). Check out the BioData West conference that will occur in SF a couple of days before our Undoing Aging conference in Berlin; I will be chairing a session on this.

We believe that the application of AI and, in particular, machine learning will prove to be a very valuable tool for research in the coming years. Such systems are ideally suited for high-throughput, laborious tasks that also require high attention to detail and would take humans a long time to do. Drug discovery, image analysis and many more tasks in the lab could potentially be automated, saving time and freeing up researchers to work on other critical tasks.

We are proud to have hosted the MouseAge project this year, which is an AI-based visual aging biomarker application that helps researchers determine the age of mice without the use of harmful tests. In a few months, researchers will be able to use the MouseAge application in the lab to help speed research progress up. This is just one example of how AI can be used in aging research and how the community helped to make it happen.

Given current funding, how far away from robust mouse rejuvenation do you think you are?

My estimate is 5-7 years, but that’s not quite “given current funding”. My overoptimism in saying “10 years” 13 years ago consisted entirely of overoptimism about funding – the science itself has not thrown up any nasty surprises whatsoever – but, nonetheless, I am quite optimistic as of now about funding, simply because the progress we have made has led to a whole new world of startups (including spinoffs from the SENS Research Foundation) and investors, so it’s not only philanthropy anymore. Plus, the increase in overall credibility of the approach is also helping to nurture the philanthropic side. We are still struggling, that’s for sure, but I’m feeling a lot surer that the funding drought’s days are numbered than I felt even two or three years ago.

Robust mouse rejuvenation (RMR) has long been a goal for the SENS Research Foundation, going back to when the SENS approach was initially proposed. RMR was originally outlined as being able to demonstrate and replicate SENS to double the remaining life expectancy of an already aged mouse. This would not mean the first RMR would be a total implementation of all the SENS approaches or that rejuvenation would need to be absolute; it would be a first pass to demonstrate the viability of multiple SENS approaches combined to produce robust results.

Being able to achieve a first-pass RMR could do much to convince academia that the repair approach to aging is plausible and attract more funding and interest in the approach. While RMR working in mice may not sound that exciting, it has huge implications for the field and potentially the rate of funding and progress.

How confident are you still in your previous prediction that humans will be able to control aging by 2029?

I think we’ve slipped a few years, entirely because of lack of funding. The tipping point will be when results in mice convince a critical mass of my curmudgeonly, reputation-protecting expert colleagues that rejuvenation will eventually work, such that they start to feel able to say so publicly. I think that’s on the order of five years away.

We think that the tipping point could well be if senolytics have the same result in humans as they have in mice. Enhanced tissue repair and regeneration in older people would be a very strong case for the repair approach to aging and almost certain to convince the academics sitting on the fence.

Certainly, if AGE breakers could be demonstrated to work in humans, this would also go a long way towards not only convincing academia but also grabbing public interest. Removing AGEs from the skin may potentially reverse wrinkles, for example, and restore skin elasticity, offering a very visual demonstration of repair being plausible.

There is almost certainly going to be a tipping point at which the bulk of academic and public support swings in favour of a repair approach to aging; the only question is when? Well, the sooner the basic science can be done and moved to translational research, the sooner we can all potentially benefit from these technologies. This makes supporting both the research and advocacy of rejuvenation biotechnology very important for progress.

 

About Dr. Aubrey de Grey

Dr. Aubrey de Grey is a biomedical gerontologist based in Cambridge, UK and Mountain View, California, USA, and is the Chief Science Officer of SENS Research Foundation, a California-based 501(c)(3) charity dedicated to combating the aging process. He is also Editor-in-Chief of Rejuvenation Research, the world’s highest-impact peer-reviewed journal focused on intervention in aging. He received his BA and Ph.D. from the University of Cambridge in 1985 and 2000 respectively. His original field was computer science, and he did research in the private sector for six years in the area of software verification before switching to biogerontology in the mid-1990s. His research interests encompass the characterisation of all the accumulating and eventually pathogenic molecular and cellular side-effects of metabolism (“damage”) that constitute mammalian aging and the design of interventions to repair and/or obviate that damage. He has developed a possibly comprehensive plan for such repair, termed Strategies for Engineered Negligible Senescence (SENS), which breaks aging down into seven major classes of damage and identifies detailed approaches to addressing each one. A key aspect of SENS is that it can potentially extend healthy lifespan without limit, even though these repair processes will probably never be perfect, as the repair only needs to approach perfection rapidly enough to keep the overall level of damage below pathogenic levels. Dr. de Grey has termed this required rate of improvement of repair therapies “longevity escape velocity”. Dr. de Grey is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organisations.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

SENS: Progress in the Fight Against Age-Related Diseases – Article by Nicola Bagalà and Steve Hill

SENS: Progress in the Fight Against Age-Related Diseases – Article by Nicola Bagalà and Steve Hill

Nicola Bagalà

Steve Hill


Editor’s Note: In this article, Mr. Nicola Bagalà and Steve Hill discuss the progress that the SENS Research Foundation has made in tackling the aging processes. Below is a brief summary of some of the highlights of their research efforts.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, December 8, 2017

 

 

Today, there are many drugs and therapies that we take for granted. However, we should not forget that what is common and easily accessible today didn’t just magically appear out of thin air; rather, at some point, it used to be an unclear subject of study on which “more research was needed”, and even earlier, it was just a conjecture in some researcher’s head.

Hopefully, one day not too far into the future, rejuvenation biotechnologies will be as normal and widespread as aspirin is today, but right now, we’re in the R&D phase, so we should be patient and remind ourselves that the fact that we can’t rejuvenate people today doesn’t mean that nothing is being done or has been achieved to that end. On the contrary, we are witnessing exciting progress in basic research—the fundamental building blocks without which rejuvenation, or any new technology at all, would stay a conjecture.

In particular, SENS Research Foundation (SRF), a pioneering organization of the field, is sometimes unjustly accused by skeptics for failing to produce results. But produce results it has, and many at that. Skeptics either decide to ignore them or do not have access to reliable sources. For the benefit of the latter, we’ll discuss below what has been achieved by SRF over the past few years, in relation to the infamous “seven deadly things”, the seven categories of damage that aging causes as described in the SENS repair approach.

Mitochondrial mutations

In a nutshell, a mitochondrion is a cell component that is in charge of converting food nutrients into ATP (adenosine triphosphate), a chemical that powers cellular function. Your DNA is contained within the nucleus of each of your cells, but this isn’t the only DNA in your body; mitochondria have their own DNA (known as mtDNA), likely because, at the dawn of life, they were independent organisms that eventually entered a symbiotic relationship with eukaryotic cells, such as those found in our bodies.

Unfortunately, as mitochondria produce ATP, they also produce so-called free radicals as a byproduct—atoms with unpaired electrons that seek to “pair up” with other electrons, and to do so, they’ll gladly snatch them from other molecules nearby, damaging them. As free radicals are created by mitochondria, they’re very close to mtDNA, which is thus very susceptible to being damaged and undergoing mutations.

Mitochondria with damaged DNA may become unable to produce ATP or even produce large amounts of waste that cells cannot get rid of. To add insult to injury, mutant mitochondria have a tendency to outlive normal ones and take over the cells in which they reside, turning them into waste production facilities that increase oxidative stress—one of the driving factors of aging.

MitoSENS: How to solve this problem, and how far we’ve got

Cell nuclei are far less exposed to free-radical bombardment than mitochondria, which makes nuclear DNA less susceptible to mutations. For this reason, the cell nucleus would be a much better place for mitochondrial genes, and in fact, evolution has driven around 1000 of them there. Through a technique called allotopic expression, we could migrate the remaining genes to the nucleus and solve the problem of mitochondrial mutations.

Human-made allotopic expression was a mere theory until late 2016, when, thanks to the successful MitoSENS crowdfunding campaign on Lifespan.io, a proof of concept was finally completed. Dr. Matthew O’Connor and his team managed to achieve stable allotopic expression of two mitochondrial genes in cell culture, as reported in the open-access paper[1] they published in the journal Nucleic Acids Research. As Aubrey de Grey himself explains in this video, of the 13 genes SRF is focusing on, it’s now managed to migrate almost four. This had never been done before and is a huge step towards addressing this aspect of aging in humans. In the past few months, the MitoSENS team has presented its results around the world and worked on some problems encountered in the project.

A list of SRF-funded papers on the topic of mitochondrial mutations can be found here. A more detailed description of its intramural MitoSENS research can be found here.

Lysosomal dysfunction

Lysosomes are digestive organelles within cells that dispose of intracellular garbage—harmful byproducts that would otherwise harm cells. Enzymes within lysosomes can dispose of most of the waste that normally accumulates within cells, but some types of waste, collectively known as lipofuscin, turn out to be impossible to break down. As a result, this waste accumulates within the lysosomes, eventually making it harder for them to degrade even other types of waste; in a worst-case scenario, overloaded lysosomes can burst open and spread their toxic contents around.

This eventuality is especially problematic for cells that replicate little or not at all, such as heart and nerve cells—they’ve got all the time in the world to become swamped in waste, which eventually leads to age-related pathologies, such as heart disease and age-related macular degeneration.

LysoSENS: How to solve this problem, and how far we’ve got

As normal lysosomal enzymes cannot break down lipofuscin, a possible therapy could equip lysosomes with better enzymes that can do the job. The approach suggested by SRF originates with ERT—enzyme replacement therapy—for lysosomal storage diseases. This involves identifying enzymes capable of breaking down different types of intracellular junk, identifying genes that encode for these enzymes, and finally delivering the enzymes in different ways, depending on the tissues and cell types involved.

SRF funded a preliminary research project on lipofuscin clearance therapeutics at Rice University[2] and another project relating to atherosclerosis and the clearance of 7-ketocholesterol[3] (a lipofuscin subtype), which eventually spun into Human Rejuvenation Biotechnologies, an early-stage private startup funded by Jason Hope.

A LysoSENS-based approach is currently being pursued by Dr. Kelsey Moody, who used to work at SRF. Dr. Moody has been working on an ERT treatment for age-related macular degeneration. The treatment consists in providing cells of the macula (a region of the eye’s retina) with an enzyme capable of breaking down a type of intracellular waste known as A2E. The treatment, called LYSOCLEAR, is being worked on by Moody’s company Ichor Therapeutics, which earlier this year has announced a series A offering to start Phase I clinical trials of its product.

If LYSOCLEAR proves successful, it could pave the way for future LysoSENS-based therapies to treat lysosomal dysfunction in different tissues.

A list of SRF-funded papers on the topic can be found here.

Cellular senescence

As cells divide, their telomeres—the end-parts of chromosomes protecting them from damage—shorten. Once a critical length has been reached, cells stop dividing altogether and enter a state known as senescence. Senescent cells are known to secrete a cocktail of chemicals called SASP (Senescence Associated Secretory Phenotype), which promotes inflammation and is associated with several age-related conditions.

However, senescent cells are a bit of a double-edged sword; as explained by Professor Judy Campisi during RB2016, as long as they’re not too numerous, senescent cells carry out an anti-cancer function and may promote wound healing; however, too many of them have the opposite effect, and on top of that, they induce neighboring cells to undergo senescence themselves, starting a dangerous spiral.

Normally, senescent cells destroy themselves via programmed cell death, known as apoptosis, and are then disposed of by the immune system, but some of them manage to escape destruction, and as the immune system declines with age, this gets worse.

The result is that late in life, senescent cells have accumulated to unhealthy amounts and significantly contribute to the development of age-related diseases. Osteoarthritis, cardiovascular diseases, cancer, metabolic disorders such as diabetes, and obesity are all linked to the chronic age-related inflammation to which senescent cells contribute.

ApoptoSENS: How to solve this problem, and how far we’ve got

The proposed SENS solution is straightforward: if senescent cells become too numerous, then they need to be purged. Since they are useful in small amounts, the optimal solution would be periodically removing excess senescent cells without eradicating them entirely—and more importantly, leaving other cells unharmed.

This could potentially be achieved by either senolytic drugs or gene therapies that selectively target senescent cells and trigger programmed cell death. Indeed, a great deal of recent focus by researchers have been on finding ways to remove senescent cells using senolytic therapies.

Another approach that could complement senolytics is to address why the immune system stops clearing senescent cells effectively in the first place. This approach focuses on macrophages and other immune cells involved in clearing senescent cells, aiming to reduce inflammation so that these cells begin to function properly again. The irony is that as inflammation rises with age, the immune system that is supposed to clear senescent cells and keep inflammation levels down actually starts to create more inflammation and becomes part of the problem by not doing its job properly.

SRF has funded a number of studies on the subject of cellular senescence, and it’s recently begun working on a project in collaboration with the Buck Institute for Research on Aging, which is focusing on the immune system and its role in clearing senescent cells. Another extramural project, again with the Buck Institute, is focussed on SASP inhibition.

Senescent cell clearance has been all the rage for the past two years or so; Lifespan.io has hosted the MMTP project, which focused on testing senolytics in mice, and this was later followed by CellAge’s project to design synthetic biology-based senolytics.

There are other companies that have joined the race to add senescent cell clearance to the standard toolkit of doctors, such as Unity Biotechnology and Oisin Biotechnologies.

Unity’s approach uses a drug-based approach to senolytics and is scheduled to enter human clinical trials in 2018. A number of other research teams are also developing drug-based approaches to removing senescent cells, and the competition looks set to be fierce in this area in the coming years.

Oisin’s approach, which we discussed here, makes use of suicide genes and hopefully will be tested in clinical trials not too far into the future, thanks to venture funding presently being collected. If this system can be made to work, it will allow very selective targeting of senescent cells by destroying only those giving off a target gene or genes. Thus, if a unique gene expression profile for senescent cells is determined, it would mean only those cells were destroyed, with less risk of off-target effects.

Oisin owes its existence to the SENS Research Foundation and the Methuselah Foundation, which provided the necessary seed funding. Kizoo Technology Ventures has also invested in Oisin.

Extracellular crosslinks

The so-called extracellular matrix is a collection of proteins that act as scaffolding for the cells in our body. This scaffolding is rarely if ever replaced, and a really bad consequence of this is that its parts eventually end up being improperly linked to each other through a process called glycation—the reaction of (mainly) blood sugar with the proteins that make up the extracellular matrix itself.

The resulting cross-links impair the function and movement of the linked proteins, ultimately stiffening the extracellular matrix, which makes organs and blood vessels more rigid. Eventually, this leads to hypertension, high blood pressure, loss of skin elasticity, and organ damage, among other problems.

While there are different types of cross-links—known as AGEs, short for advanced glycation end-products—glucosepane is arguably the worst, being the most common and long-lasting of all, and the body is very ill-equipped to break it down.

GlycoSENS: How to solve this problem, and how far we’ve got

In order to eliminate unwanted cross-links, the SENS approach proposes to develop AGE-breaking molecules that may indeed sever the linkages and return tissues to their original flexibility. Of course, in order to do so, crosslink molecules need to be available for research to attempt to combat them with drugs, and especially in the case of glucosepane, this has been a problem for years.

Glucosepane is a very complex molecule, and very little of it can be extracted from human bodies, and not even in its pure form. This has been greatly hampering the progress of research against glucosepane, but thankfully, this problem is now solved thanks to a collaboration between the Spiegel Lab at Yale University and the SENS Research Foundation, which financially supported the study. It is now possible to fully synthesize glucosepane, allowing for researchers to create it on demand and at a cost-effective price.

The Spiegel Lab’s scientists are now developing anti-glucosepane monoclonal antibodies to cleave unwanted cross-links. The collaboration between the Spiegel Lab and SRF dates all the way back to 2011, but it was in 2015 that the Lab announced its success and published a related paper [4] in the journal Science.

Further information on glucosepane cross-link breakers can be found in this interview with Dr. David Spiegel from Yale University on Fight Aging!; a list of studies on the subject funded or otherwise supported by the SRF is available here.

SRF also worked with the Babraham Institute on a cross-link quantification project.

Let’s help SRF move forward

Readers who wish to donate to SRF to help the organization in its crusade against the ill health of old age can do so by contributing to its winter fundraiser or even becoming SRF patrons. Have a look at SRF’s donation page to find out more.

NB: Dr. Aubrey de Grey (Chief Science Officer and Co-founder of SENS Research Foundation) himself held an AMA (“ask me anything”) on Reddit on December 7, at 14:00 PST (22:00 UTC, 17:00 EST). The questions and Dr. de Grey’s responses can be found here.

Literature

[1] Boominathan, A., Vanhoozer, S., Basisty, N., Powers, K., Crampton, A. L., Wang, X., … & O’Connor, M. S. (2016). Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant. Nucleic acids research, 44(19), 9342-9357.

[2] Gaspar, J., Mathieu, J., & Alvarez, P. (2016). A rapid platform to generate lipofuscin and screen therapeutic drugs for efficacy in lipofuscin removal. Materials, Methods and Technologies, 10, 1-9.

[3] Mathieu, J. M., Wang, F., Segatori, L., & Alvarez, P. J. (2012). Increased resistance to oxysterol cytotoxicity in fibroblasts transfected with a lysosomally targeted Chromobacterium oxidase. Biotechnology and bioengineering, 109(9), 2409-2415.

[4] Draghici, C., Wang, T., & Spiegel, D. A. (2015). Concise total synthesis of glucosepane. Science, 350(6258), 294-298.

 

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Why Bringing Aging Under Medical Control Probably Will Not Create a Gerontocracy – Article by Nicola Bagalà

Why Bringing Aging Under Medical Control Probably Will Not Create a Gerontocracy – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà discusses Gerontocracy and how it is becoming less likely due to factors such as increasing wide availability of knowledge and equal opportunities.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                      ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, December 05, 2017

 

As I discussed in another article, rejuvenation biotechnology would allow older adults to continue working and producing wealth for much longer than they can today, thus benefiting society in many ways.

However, some people are concerned that this might do more harm than good; imagine all those rejuvenated old farts holding onto their jobs forever, preventing the young from getting jobs themselves! Not to mention the risk of a gerontocratic world, where powerful older people get too attached to their chairs, never allowing younger people a chance!

New is not always better

If you’re more concerned that dictators could live for centuries, then you should have a look at this article; here, I’m going to deal with another scenario: old, rejuvenated people who hold on to positions of power—not necessarily as heads of countries—or their jobs for a really long time.

Quite frankly, what’s wrong with that?

Just because someone has been in charge of the same position for long, it doesn’t mean that it’s necessarily a bad thing. If you think otherwise, you might be making the assumption I rebutted here, namely that, rejuvenated or not, older people will always tend to do things in old ways, eventually making them a worse choice than younger people. On the contrary, their long experience might make them more fit than others, especially if we’re talking about chronologically older but open-minded people who keep up to date. Younger people aren’t necessarily the default better option. Think about all those times when a great person of our time died and you found yourself thinking that the world would have been better off if he or she had lived longer.

Personally, I think what matters is that people in certain positions, whether within government or a company, are the right people for the job. If they aren’t, old or young, they should be replaced by other people who are more fit, and, generally, there are more efficient and humane ways to do so than letting them get age-related diseases—for example, voting for someone else or hiring a different person. Granted, if the person to be kicked out is really powerful, this may well be easier said than done; however, when the holder of a position of such power dies of old age, his successor is rarely a nobody with no string-pulling abilities whatsoever. It’s not really a matter of longevity; rather, it’s that power attracts power, and I doubt that creating or not creating rejuvenation will make much of a difference in this respect.

Where does power come from?

It’s easy to hypothesize that a generation of rejuvenated 200-year-olds could end up becoming a gerontocratic elite that maintains power over younger people, but how would this be accomplished, exactly?

Maybe the older generation is rich and powerful, but unless we’re talking about a totalitarian world in which the masses are intentionally kept ignorant and poor, younger generations do have fair chances to make positions for themselves. Power and wealth come from knowledge, and, these days, knowledge is more freely and widely available than ever before.

Learning new professional skills and acquiring knowledge, in general, is possible for virtually everyone, thanks to the pervasiveness of educational media and the open availability of information on the Internet, including free (or reasonably affordable) online education projects, such as Coursera and Edx. The recent European initiative to ensure that all scientific papers are open access by 2020 represents another step towards a world that shares information rather than hides it.

Truth to be told, power and wealth don’t come only from knowledge; they also come from powerful and wealthy ancestors. If we didn’t develop rejuvenation, certainly all the Scrooge McDucks of the world would die sooner than they would otherwise, but their power and wealth would go to their heirs, and so on over the generations, which wouldn’t do much to prevent the creation of an elite. So, no, old age is not an easy way out of the problem of powerful elites ruling the world, and its absence wouldn’t make the problem any worse, really. The only possible way out is giving everyone equal access to knowledge and equal opportunities.

Inevitably, some will end up being more successful and thus more powerful than others anyway; however, if this allows them to become an oppressive force on the rest of us, I think this is a problem with our socio-economic system, not with the existence of lifesaving medical technology. I don’t know about you, but I’m not very keen on waiting until the “perfect” society or “perfect” economic system are built before we decide to cure the diseases of old age.

The fortune teller’s error

We shouldn’t make the mistake of predicting a negative outcome without considering the actual odds of it happening. I think fears of a society where rejuvenated elderly make younger people’s lives more difficult are misplaced in that they assume present-day scenarios will exist in the far future.

Take the concern about jobs, for example, rejuvenated old people would stick to their jobs forever and make it harder for young people to enter the workforce. It sounds bad, but there are a few assumptions behind it that we should question.

First, would rejuvenated old people actually stick to their jobs forever? Why? You hardly hear of a professional who was in the exact same job for forty years these days. More broadly, career change is a thing already. After all, after 40 years in the same line of work, it’s conceivable you might want to try something else, thus making room for others to take your place.

Will rejuvenated old people be allowed to stick to their jobs forever? Not everyone is a manager in charge of decisions, and your boss may well decide to lay you off, rejuvenated or not, and hire someone else.

Even if old rejuvenated people did stick to the same jobs forever, would they never take a break? Even if you’re in the prime of health, after a few decades, you may well wish to “retire” for a few years before going back to work, and your employer is probably not going to wait for you that long.

Will there be so many chronologically younger people in need of jobs in the future? The world population growth rate has been hopelessly corkscrew-diving for over 50 years now, and it is projected to keep going down as larger portions of the world transition from a developing to a developed economy. (In case you’re wondering, the population growth rate is going down not because more people die, but on the contrary, because fewer are born.)

Will people’s living depend on having a job in the future? We can’t expect indefinite life extension to happen very soon; before we can have 200-year-old people in the workforce, it’ll be at least a century. Is the economy going to be the same as today’s by then? Automation already seems on its way to cause the end of work as we know it.

I’d say it’s rather silly to oppose rejuvenation today for the reason that, in a century or two, it might cause an unemployment problem due to too many people being alive. It’s simply too long a time to make any even remotely accurate predictions on what the job market will be like or if there even will be any. In all honesty, I think it makes more sense to worry about a concrete problem that we already have today—the ill health of old age—than worry about a hypothetical one that might or might not happen in a hundred years’ time—massive unemployment. As time goes by, we’ll have a better picture of potential future problems lying ahead, and we’ll be in a better position than we are in today to do something about them.

Conclusion

I’ve said this many times over: the bottom line is always the same. Yes, life extension will most likely bring challenges along with benefits, but none of these challenges are certain, insurmountable, or not more than compensated for by the expected benefits. Let’s not deny ourselves and our descendants the chance for healthier, longer lives.

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

We are the Lifespan – Video and Commentary by the Life Extension Advocacy Foundation

We are the Lifespan – Video and Commentary by the Life Extension Advocacy Foundation

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Life Extension Advocacy Foundation


The U.S. Transhumanist Party is pleased to share this message and video from our allies at LEAF – the Life Extension Advocacy Foundation. The video includes a short clip of remarks from U.S. Transhumanist Party Chairman Gennady Stolyarov II, taken from his video for the “I am the Lifespan” campaign.


As you might remember, during the month of October (often called Longevity Month) we at LEAF were accepting videos to hear your reasons why defeating the diseases of aging is so important — and hear from you we did!

Dozens of videos poured in, and this #GivingTuesday we at LEAF are so proud to share with you all a video that shows how strong we can be when we join forces for longer, healthier lives — how together #WeAreTheLifespan.

Thank you so much for raising your voice with us in support of longevity research, and if you wish to continue to help us please feel free to join our Hero campaign or to participate in Facebook’s #GivingTuesday donation match by clicking any of the donate buttons on our Facebook page or posts. If you want to get creative, you can even make your own fundraisers easily on Facebook on posts or with a live video.

Finally, to illustrate the importance of speaking freely on what you care about, we are pleased to let you know of the developments related to the recent Open Consultation on the 13th draft programme of work of the WHO. As we wrote not long ago, the problems related to population aging and corresponding health and social issues were left out of the draft, and we invited the members of the community to step in and recommend an improvement.

90% of responses during the Open Consultation (out of around 400 responses) underlined the need to make healthy longevity one of the priorities for the 13th programme of work, and the WHO have recognized this. A joint effort of many pro-longevity organizations made that happen.

Each voice matters. Your voice matters. So please, keep being active and vocal, and let’s become the generation who can say: “I helped set all people free from age-related diseases. I helped defeat aging.”

Thank you, and happy #GivingTuesday!

Stem-Cell Clinical Trials Show Remarkable Results Against Age-Related Frailty – Article by Steve Hill

Stem-Cell Clinical Trials Show Remarkable Results Against Age-Related Frailty – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill discusses two very promising human clinical trials using stem cell therapy for age-related frailty. This article was originally published by the Life Extension Advocacy Foundation (LEAF) .

~ Kenneth Alum, Director of Publication, U.S. Transhumanist Party, October 29, 2017

The first results of two human clinical trials using stem cell therapy for age-related frailty have been published, and the results are very impressive indeed. The studies show that the approach used is effective in tackling multiple key age-related factors.

Aging research has made significant progress in the last few years, with senescent-cell-clearing therapies entering human trials this year, DNA repair in human trials, and a number of other exciting therapies nearing human testing. We are reaching the point where therapies that target aging processes are no longer a matter of speculation; they are now an undeniable matter of fact.

What are mesenchymal stem cells?

Mesenchymal stem cells (MSCs) are one of the most commonly used types of stem cells in therapy. MSCs are adult stem cells that can become other types of cells, depending on stimulus; this ability to become a variety of other cell types is known as multipotency. [1]

The cells into which MSCs can transform (differentiate) include osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells), and adipocytes (fat cells). MSCs are of great interest to aging researchers and are arguably one of the most well studied and understood types of stem cells. [2]

MSCs are currently in various trials to treat conditions such as cancer, heart disease, and arthritis. [3] The potential of MSCs for treating neurodegenerative diseases, such as Alzheimer’s, are also being explored in preclinical testing. [4-5]

A therapy for age-related frailty

The focus of the MSC therapy in the case of these two clinical trials is to reduce the effects of age-related frailty on senior citizens. This also marks an important step for rejuvenation biotechnology, as this is the first stem-cell treatment that is close to final FDA approval for specifically targeting age-related frailty. Should this be approved, then it opens the door for other similar approaches and the potential treatment of many age-related diseases.

The therapy itself uses MSCs taken from adult donor bone marrow and is infused into patients with an average age of 76 years old. The good news is that patients in both the phase 1 and phase 2 clinical trials have shown no adverse effects to treatment.

This is excellent news and now paves the way to move to phase 3 clinical trials, which are larger-scale tests to further determine the efficacy and compare it to the best currently available treatments, for which there are basically none beyond simple coping approaches, such as walking sticks and frames to compensate for frailty.

It is also important to note that at this at this point, the drug or therapy is accepted as having some effect. You can read more about the clinical trial process and what each phase means here.

In the first trial, 15 patients with age-related frailty were given a single transplant of MSCs from donors aged between 20 and 45. [6] Six months later, all patients in the trial showed an improved level of fitness, lower levels of inflammatory tumor necrosis factor (TNF), and improved quality of life in general. TNF is one of the regulators of inflammation and contributes to the chronic age-related inflammation known as “inflammaging”, which drives a number of age-related diseases. [7]

The second trial was a randomized, double-blind study including a placebo group. An improved physical performance level was observed in patients, and, again, the level of systemic TNF, and thus inflammation, was reduced. [8] Once again, there were no adverse effects observed in the patients, and the researchers wrote:

Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome.

David G. Le Couter and colleagues have written about the clinical trials in a guest editorial in The Journals of Gerontology:

There are always caveats associated with interpreting efficacy in small numbers of subjects, yet it is remarkable that a single treatment seems to have generated improvement in key features of frailty that are sustained for many months.

The next step for the researchers here is to begin a phase 2b clinical trial with 120 patients in ten different locations. Following the conclusion of this, a large randomized phase 3 trial will be launched, and this will be the final barrier to public approval for the therapy.

Conclusion

With an ever-increasing number of aged people in our population, stem cells hold great potential for treating a number of age-related diseases and combating the disability and frailty that accompany the aging process. Developing therapies like these could potentially help older people to enjoy an improved level of physical performance and a better quality of life. Being able to remain mobile and independent as we grow older would be of huge benefit to not only the individual but also to families and society as a whole.

There are currently no FDA-approved treatments for age-related frailty, so this represents a huge unmet need that will only worsen with an increasingly aging population if those needs are not met by new medicines.

Seeing such tangible results in humans is a clear indication of the potential of rejuvenation biotechnology, and how we regard and treat aging will be changing in the near future.

Literature

[1] Nardi, N. B., & da Silva Meirelles, L. (2008). Mesenchymal stem cells: isolation, in vitro expansion and characterization. In Stem cells (pp. 249-282). Springer Berlin Heidelberg.

[2] Stolzing, A., Jones, E., McGonagle, D., & Scutt, A. (2008). Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mechanisms of ageing and development, 129(3), 163-173.

[3] Wang, S., Qu, X., & Zhao, R. C. (2012). Clinical applications of mesenchymal stem cells. Journal of hematology & oncology, 5(1), 19.

[4] Danielyan, L., Beer-Hammer, S., Stolzing, A., Schäfer, R., Siegel, G., Fabian, C., … & Novakovic, A. (2014). Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer’s and Parkinson’s disease. Cell transplantation, 23(1), S123-S139.

[5] Naaldijk, Y., Jaeger, C., Fabian, C., Leovsky, C., Blüher, A., Rudolph, L., … & Stolzing, A. (2017). Effect of systemic transplantation of bone marrow‐derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice. Neuropathology and applied neurobiology, 43(4), 299-314.

[6] Golpanian, S., DiFede, D. L., Khan, A., Schulman, I. H., Landin, A. M., Tompkins, B. A., … & Levis-Dusseau, S. (2017). Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, glx056.

[7] Franceschi, C., Garagnani, P., Vitale, G., Capri, M., & Salvioli, S. (2017). Inflammaging and ‘Garb-aging’. Trends in Endocrinology & Metabolism, 28(3), 199-212.

[8] Tompkins, B. A., DiFede, D. L., Khan, A., Landin, A. M., Schulman, I. H., Pujol, M. V., … & Mushtaq, M. (2017). Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(11), 1513-1522.

 

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Why Rejuvenation Biotechnology Could Benefit You – Article by Nicola Bagalà

Why Rejuvenation Biotechnology Could Benefit You – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà discusses the benefits of Rejuvenation Biotechnology (age-reversing technology).  This article was originally published by the Life Extension Advocacy Foundation (LEAF) .

~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, October 25, 2017

The benefits are many; some are obvious, and some are less so. The ones I’ll discuss in this article are the ones I see as obvious, tangible, immediate benefits for the people undergoing rejuvenation.

Health

We’ve kind of made a rather big deal of this one, haven’t we? Rejuvenation, we have said time and again, is pretty much all about health. The causal link between biological aging and pathologies is well established, and even when we account for the few elderly who are exceptionally healthy for their age, we’re left with the obvious fact that the older you are, the sicker you are, and even the aforementioned exceptions aren’t in the best of shape.

To the best of my knowledge, the number of people who actively wish to be sick at some point tends to be fairly small; so, when you think that a truly comprehensive rejuvenation platform would allow people to maintain youthful health irrespective of their age, the health benefits of rejuvenation become crystal clear. To be honest, this benefit alone would be enough for me, and I wouldn’t even need to look into the other ones.

Independence

Frailty, failing senses, weakness, and diseases aren’t good friends of independence, but they are good friends of old age. That’s why nursing homes exist in the first place to take care of elderly people who are no longer independent. Again, even the few exceptional cases who manage on their own until death don’t have it easy. Having people doing things for you can be nice in small doses, but having to have people doing things for you, not so much. Rejuvenation would eliminate the health issues that make the elderly dependent on others, which is a rather evident benefit.

Longevity

As odd as it may sound, longevity is really just a ‘side effect’ of health, because you can’t be healthy and dead. The longer you’re healthy enough to be alive, the longer you’ll live. Since rejuvenation would keep you in a state of youthful health, the obvious consequence is that you’d live longer. How much longer exactly is hard to say, but as long as you’re healthy enough to enjoy life, it’s safe to say that longevity would be a benefit; you’d have more time and energy to dedicate to what you love doing, and you could keep learning and growing as a person for an indefinitely long time.

You would not have to worry about the right age to change your job, get married, or start practicing a new sport, because your health wouldn’t depend on your age, and the time at your disposal would not have a definite upper limit. If the first few decades of your life weren’t as good as they could have been for one reason or another, you would still have time ahead and a chance of a better future, which sounds more appealing than ten years in a hospice with deteriorating health to me. (Let’s face it: If your life isn’t very good to begin with, a disease is hardly going to make it better.)

Additionally, a longer life would allow you to see what the future has in store for humanity. I wouldn’t be too quick to think the future will be all doom and gloom.

Today’s world is more peaceful and prosperous than it was in the past, and while there’s no certainty it will be at least this good in the future, there’s no certainty that it won’t be worth living in either. I would argue it’s best not to cross our bridges before we get there, and we shouldn’t opt out of life before we actually reach a point when we don’t care for it anymore, if ever.

I don’t think I will ever have a reason to give up on life or get bored with it, but I accept that somebody might think otherwise. Even so, I think being able to choose how long you want to live, and always living in the prime of health, is a much better deal than the current situation of having a more-or-less fixed lifespan with poor health near the end.

Choice

Ultimately, all of these perks can be summarised into one: choice. If we had fully working rejuvenation therapies available and were thus able to keep ourselves always perfectly healthy, regardless of our age, we could choose whether we wanted to use these therapies or not. Those who wish a longer, healthier life could avail themselves of the opportunity and escape aging for as long as they wanted; those who prefer to age and bow out the traditional way could just as easily not use the therapies.

Rejuvenation would give us an extra option we currently don’t have; everyone is forced to face the burden of aging and eventually die of it, for the moment. Being able to choose what we wish for ourselves is one of the most fundamental human rights and an obvious, unquestionable benefit.

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

U.S. Transhumanist Party Q&A Session – October 21, 2017

U.S. Transhumanist Party Q&A Session – October 21, 2017

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Gennady Stolyarov II
Martin van der Kroon
Sean Singh
B.J. Murphy


In this interactive question-and-answer session, which occurred at 1 p.m. U.S. Pacific Time on Saturday, October 21, 2017, U.S. Transhumanist Party Officers provided an updated view of the Transhumanist Party’s projects, operations, and achievements, in response to audience questions. Because October is Longevity Month, this Q&A session had a life-extension theme but also delved into various other areas, including how to address conspiracy theories and various approaches toward diet, nutrition, and cultural norms regarding food consumption. The Q&A session has been archived on YouTube here.

The following U.S. Transhumanist Party Officers took part in this Q&A session:

– Gennady Stolyarov II, Chairman
– Martin van der Kroon, Director of Recruitment
– Sean Singh, Director of Applied Innovation
– B.J. Murphy, Director of Social Media

The YouTube question/comment chat for this Q&A session has been archived here and is also provided below.

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Hallmarks of Aging: Epigenetic Alterations – Article by Steve Hill

Hallmarks of Aging: Epigenetic Alterations – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill discusses one of the hallmarks of aging – in this case, Epigenetic Alterations. It is part of a paper published in 2013. It divides aging into a number of distinct categories (“hallmarks”) of damage to explain how the aging process works and how it causes age-related diseases [1]. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                        ~ Kenneth Alum, Director of Publication, U.S. Transhumanist Party, October 18, 2017

What are epigenetic alterations?

The DNA in every one of our cells is identical, with only small variations, so why do our various organs and tissues look so different, and how do cells know what to become?

DNA is modified by the addition of epigenetic information that changes the pattern of gene expression in a cell, suppressing or enhancing the expression of certain genes in a cell as the situation demands. This is how a cell in the liver knows that it needs to develop into a liver cell; the epigenetic instructions make sure that it is given the right orders to become the correct cell type.

At a basic level, these epigenetic instructions make sure that the genes needed to develop into a liver cell are turned on, while the instructions specific to other types of cells are turned off. Imagine if a heart cell was given the wrong instructions and became a bone cell!

How epigenetic alterations accumulate

The aging process can cause alterations to our epigenome, which can lead to alterations in gene expression that can potentially change and ultimately compromise cell function. As an example, epigenetic alterations of the immune system can harm activation and suppress immune cells, thus causing our immune system to fail and leaving us vulnerable to pathogens.

Inflammation is implicated in epigenetic alterations, and studies show that caloric restriction slows the rate of these epigenetic changes [2]. Metabolism and epigenetic alterations are closely linked with inflammation, facilitating a feedback loop leading to ever-worsening epigenetic alterations. Alterations to gene expression patterns are an important driver of the aging process. These alterations involve changes to DNA methylation patterns, histone modification, transcriptional alterations (variance in gene expression) and remodeling of chromatin (a DNA support structure that assists or impedes its transcription).

In the cell, gene expression is activated by hypomethylation (a loss of methylation) or silenced by hypermethylation (an increase of methylation) at a gene location. The aging process causes changes that reduce or increase methylation at different gene locations throughout the body. For example, some tumour suppressor genes become hypermethylated during aging, meaning that they cease functioning, which increases the risk of cancer [3]. Post-translational modifications of histones regulate gene expression by organizing the genome into active euchromatin regions, where DNA is accessible for transcription, or inactive heterochromatin regions, where DNA is compacted and less accessible for transcription. The aging process causes changes to these regions, which changes gene expression.

The aging process also causes an increase in transcriptional noise, which is the primary cause of variance in the gene expression happening between cells [4]. Researchers compared young and old tissues from several species and identified age-related transcriptional changes in the genes encoding key components of inflammatory, mitochondrial, and lysosomal degradation pathways [5].

 Finally, chromatin remodeling alters chromatin from a condensed state to a transcriptionally accessible state, allowing transcription factors and other DNA binding proteins to access DNA and control gene expression.

Conclusion

If we can find ways to reset age-related epigenetic alterations, we can potentially improve cell function, thus improving tissue and organ health.

One potential approach is the use of reprogramming factors, which reset cells to a developmental state, thus reverting epigenetic changes. We have been doing this for over a decade to create induced pluripotent stem cells, and recent work has seen a therapy based on that technique applied to living animals to reset their epigenetic alterations [6]. This reversed a number of age-related changes, and work is now proceeding with the goal of translating this to humans.

Epigenetic alterations might be considered like a program in a computer, but in this case, it is the cell, not a computer, being given instructions. Ultimately, damage causes changes that contribute to the cell moving from an efficient “program” of youth to a dysfunctional one of old age. If we can reset that program, we can potentially address this hallmark of aging, and a number of researchers are working on that right now.

 

Literature

[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[2] Maegawa, S., Lu, Y., Tahara, T., Lee, J. T., Madzo, J., Liang, S., … & Issa, J. P. J. (2017). Caloric restriction delays age-related methylation drift. Nature Communications, 8.
[3] Maegawa, S., Hinkal, G., Kim, H. S., Shen, L., Zhang, L., Zhang, J., … & Issa, J. P. J. (2010). Widespread and tissue specific age-related DNA methylation changes in mice. Genome research, 20(3), 332-340.

[4] Bahar, R., Hartmann, C. H., Rodriguez, K. A., Denny, A. D., Busuttil, R. A., Dollé, M. E., … & Vijg, J. (2006). Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature, 441(7096), 1011-1014.

[5] De Magalhães, J. P., Curado, J., & Church, G. M. (2009). Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics, 25(7), 875-881.

[6] Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., … & Araoka, T. (2016). In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. Cell, 167(7), 1719-1733.

 

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Hallmarks of Aging: Genomic Instability – Article by Steve Hill

Hallmarks of Aging: Genomic Instability – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill discusses one of the hallmarks of aging – in this case, Genomic Instability. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

~ Kenneth Alum, Director of Publication, U.S. Transhumanist Party, October 17, 2017

What is genomic instability?

The cells of your body produce a constant flow of proteins and other materials; these are built according to the blueprints contained in our DNA and are vital to cell function and survival. A large amount of information contained in the DNA is ignored during this process, and this is thought to be junk DNA, remnants of our evolutionary past that are no longer used.

However, if a part of the DNA important to cell function mutates or is damaged, the cell can experience a loss of proteostasis, in which the cell produces misfolded proteins. These misfolded proteins can be very harmful, such as when neurons in the brain produce masses of the toxic amyloid beta protein, as seen in Alzheimer’s disease.

Now, the odd dysfunctional cell is not really a huge problem; however, as we get older, an increasing number of cells succumb to this damage and begin to accumulate in tissue over time. Eventually, the number of these damaged cells reaches a point where tissue or organ function is compromised. Normally, the body removes these problem cells via a self-destruct sequence known as apoptosis, a sort of kill switch that senses the damage and destroys the cell in conjunction with the immune system.

Unfortunately, some cells evade apoptosis, taking up space in the tissue and pumping out inflammatory signals that damage the local tissue. These cells are known as senescent cells, and we will be covering them in a later Hallmarks article.

Another possible outcome of damaged DNA is cells that mutate and do not become senescent cells or destroy themselves via apoptosis. These cells continue to replicate, becoming more mutated each time they divide, and if a mutation damages the systems that regulate cell division or switches off the safety mechanisms against tumor formation, this can lead to cancer. The unchecked and rampant cell growth of cancer is probably the most well-known result of genomic instability.

How DNA damage accumulates

There are many ways for DNA to become damaged. UV rays, radiation, chemicals, and tobacco are all examples of environmental stressors that can damage the genome. Even chemotherapy agents designed to kill cancer can also potentially cause DNA damage and senescent cells, leading to later relapse [2].

Finally, even if we avoided all the external threats to our DNA, the body still damages itself. Reactive oxygen and nitrogen species produced during the operation of normal metabolism can damage both DNA and mitochondrial DNA.

Thankfully, we have evolved a robust network of repair systems and mechanisms that can repair most of this damage. We have enzymes that can detect and repair broken strands of DNA or reverse alterations made to base pairs. This repair process is not perfect, and sometimes the DNA is not repaired. This can lead to the cell replication machinery misreading the information contained in the DNA, causing a mutation.

As mutations are passed to daughter cells, the cell tries to prevent this from happening by checking DNA integrity before and after replication. Unfortunately, some cells do manage to slip through the net.

The consequences of DNA damage

A large number of age-related diseases are linked to damaged DNA or faulty DNA repair systems. Alzheimer’s, Parkinson’s, Lou Gehrig’s disease (ALS), and cancer are all the result of genomic instability.

Another example are the progeric diseases. Progerias are congenital disorders that result in rapid aging-like symptoms and a dramatically shortened lifespan, with Hutchinson-Gilford progeria syndrome (HGPS) probably being the most well known. The disease is caused by a defect in Lamin A, a major component of a protein scaffold on the inner edge of the nucleus called the nuclear lamina. The lamina helps organize nuclear processes, such as RNA and DNA synthesis, and lamins are responsible for supporting key proteins in the DNA repair process.

This defect leads to HGPS sufferers only living until their early 20s and developing atherosclerosis, stiff joints, hair loss and wrinkles, and other accelerated aging-like characteristics.

Conclusion

Despite the various repair systems we have evolved, our body is constantly being assaulted from exposure to environmental stressors and even damaged through its own metabolic processes. Coupled with this, our repair systems also decline in effectiveness over time, meaning that DNA damage and mutations are inevitable.

There is some evidence to suggest that caloric restriction may help combat this, but as of now, no drugs or therapies are available yet that can prevent or repair DNA damage. The good news is human trials for DNA repair are launching this year at Harvard, and Dr. David Sinclair and other researchers are also working on their own solutions.

For the time being, the best we can do is to avoid risks, such as excessive sun exposure, industrial chemicals, smoking, and, of course, staying away from radioactive waste; there are no comic-book superpowers from these mutations!

Literature

[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[2] Demaria, M., O’Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., … & Alston, S. (2017). Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer discovery, 7(2), 165-176.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

The Good Sides of Aging? – Article by Nicola Bagalà

The Good Sides of Aging? – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: Nicola Bagalà in this guest article elaborates upon aging as a topic distinguished in terms of Chronological Aging and Biological Aging. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

~ Kenneth Alum, Director of Publication, U.S. Transhumanist Party, October 17, 2017

Sometimes, and especially in articles aimed at mitigating people’s fear of aging, it is said that aging doesn’t come just with downsides, such as frailty and diseases, but also with upsides — for example, wisdom and a long life experience.

It is often subtly implied that these two very different aspects are two sides of the same coin, that you can’t have one without the other, and perhaps even that the ill health of old age is a fair price to pay for the benefits that also come with it.

Nothing could be further from the truth.

Setting the record straight

There are plenty of good reasons to be afraid of aging, because the diseases and disabilities it causes are very real and far from being observed only in exceptional cases. It would be foolish not to fear cancer, for example, because it is an extremely serious and often fatal condition; in the same way, and for the same reasons, it is foolish not to fear aging; perhaps, an even stronger fear is justified, because aging can and does give rise to many diseases, including cancer itself.

There’s nothing wrong with fearing aging, because it may help us steer clear from its inherent dangers, just like the fear of any other harmful thing keeps us away from it. This is true so long as by ‘aging’ we mean biological aging, which is not at all the same as chronological aging. It is very important to draw a line between the two so that we don’t end up accepting the downsides of the former, which are neither necessary nor sufficient to enjoy the benefits of the latter.

What’s the difference?

Chronological aging is a rather fancy term to indicate a very mundane thing, namely the passing of time. For as long as time will keep passing, everything will age chronologically. This is obviously a good thing because if time did not pass, the universe would stand still and nothing at all, including ourselves, would ever happen.

However, it is easy to see how chronological and biological aging are not the same thing by means of a simple observation: Although time runs essentially uniformly everywhere on Earth, different life forms have different health- and lifespans. If time passes at the same rate for me and for a cat, and yet I’m (biologically) old at age 80 while a cat is (biologically) old already at age 15, clearly there must be something else than just the passing of time that accounts for this discrepancy.

This ‘something else’ is metabolism—the intricate set of chemical reactions the bodies of living creatures perform on a daily basis for the very purpose of staying alive. As we have discussed in other articles, what we call biological aging is really just a process of damage accumulation; this damage, which eventually leads to pathologies, is caused by metabolism itself, and therefore a faster metabolism means faster aging. Different species have different metabolic rates; as a rule of thumb, the smaller the species, the faster its metabolism and thus its aging, leading to shorter health- and lifespan. This is, in a nutshell, why a cat ages faster than I do.

As a confirmation of this fact, one may observe that species in a regimen of caloric restriction tend to live longer (sometimes much longer) than their normal lifespan, and the insurgence of age-related diseases is delayed accordingly: A lower caloric intake causes metabolism to slow down; consequently, the aging process follows suit.

Interestingly, some lucky species, the so-called negligibly senescent organisms, don’t show any signs of biological aging at all with the passing of time.

At this point, you don’t have to be clairvoyant to see that biological aging implies chronological aging, but not vice-versa. No chronological aging means no time passing, and no time passing means nothing takes place, metabolism included. However, since different creatures age differently (or not at all) despite time passing at the same rate for all of them, chronological aging doesn’t imply biological aging. Quite simply, they’re not the same thing.

Render unto Caesar the things which are Caesar’s

Having cleared the difference between chronological and biological aging, we must now correctly attribute the aforementioned pros and cons of old age to each of them.

From the very definition of biological aging above, it’s clear that it is the culprit responsible for the cons—the diseases of old age.

Speaking of the pros, all possible benefits of old age—life experience, wisdom, sense of accomplishment—certainly do not come from the damage that metabolism has wrecked throughout your body over the years. Clearly, they depend on the events of your life, and thus they’re not at all granted to happen, no matter how long you live. If you spent your life in isolation doing nothing, avoiding new experiences, and not learning anything new, your wisdom as an eighty-year-old would hardly compare to that of a well-traveled, seasoned scientist or philosopher of the same age, for example. Ultimately, the benefits traditionally attributed to old age obviously depend on the passing of time (i.e., chronological aging), and most of all on the use you made of your time. Just because you’re old, you’re not automatically wise, accomplished, or well-learned.

What’s more, the debilitation that comes with biological aging makes it harder for you to relish and expand the wisdom and experience you’ve accrued over the years. So, not only does biological aging bring no benefits; it is a hindrance as well.

In conclusion, the pros and cons of old age are due to different causes, and, as such, they aren’t interdependent. The diseases of old age are not a currency you can use to buy yourself the wisdom of the aged, and thanks to the emergence of rejuvenation biotechnologies, you might relatively soon be able to enjoy the pros of old age without having to pay any undue and unfair tolls.

 

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age-related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them—which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.