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Month: June 2019

U.S. Transhumanist Party Presidential Primary Candidates Johannon Ben Zion and Rachel Haywire Discuss Policy, the Democratic Debates, and Transhumanist Advocacy

U.S. Transhumanist Party Presidential Primary Candidates Johannon Ben Zion and Rachel Haywire Discuss Policy, the Democratic Debates, and Transhumanist Advocacy

Johannon Ben Zion
Rachel Haywire


Two 2020 Third-Party Candidates dissect the “First Democratic Debate” from Johannon Ben Zion on Vimeo.

On June 28, 2019, two of the U.S. Transhumanist Party / Transhuman Party Presidential primary candidates, Rachel Haywire and Johannon Ben Zion, conversed about the juxtaposition of techno-progressive and public-health goals, policy-making, and organizing.

This thoughtful and constructive policy-oriented discussion is a worthy precursor to the forthcoming July 6 Virtual Debate (which the public can watch here), where candidates including Johannon Ben Zion and Rachel Haywire (as well as Charles Holsopple and Dan Good) will be articulating their visions of transhumanist policy to the public. The caliber and civility of discourse in the Ben Zion / Haywire conversation stand out as being immensely higher than what was observed during the Democratic primary debates, where it seems that many of the candidates were at one another’s throats. Once again, transhumanists have shown that they can do better. This discussion is a valuable building block for the outcome that we hope will happen once the U.S. Transhumanist Party / Transhuman Party Electronic Primary is concluded in mid-August – that all of the candidates will collaborate with the nominee, no matter who wins, and work toward maximizing the influence and impact of transhumanist ideas and policy proposals.

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.

Popular Reactions to Life Extension – Article by Nicola Bagalà

Popular Reactions to Life Extension – Article by Nicola Bagalà

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 31st, 2018. In this article, Mr. Bagalà examines two studies from 2009, in which researchers interviewed members of the public regarding their opinions of life-extension research. This is an excellent read if you want to peer into how people in the past felt about life extension. 

~ Bobby Ridge, Assistant Editor, June 28, 2019

Two papers by Partridge et al [1, 2], both published in 2009, provide the somewhat rare opportunity to examine some concerns about life extension as formulated by actual people, rather than their general, more abstract forms.

As highlighted in the studies, research on the public’s perception of life extension science has been very much neglected; this, in turn, has made it harder to identify the misconceptions and incorrect information fueling some common concerns about life extension and made it even harder to address those very concerns. Needless to say, the more that the public views life extension negatively, the less supportive that it will probably be, which is bad news for researchers.

The papers present the results of several interviews, conducted either in person or on the phone, aimed at understanding what ethical concerns the interviewees had about life extension and what implications they thought extended human lifespans would have for themselves and for society. The research was conducted on a sample of the Australian population only, but the issues they raised were entirely representative of a typical discussion about life extension. In both studies, the interviewees were presented with the general premise of possibly slowing down aging and the onset of age-related diseases in order to greatly extend human healthy lifespan.

We’ll be taking a look at specific claims made or sentiments expressed by different interviewees in both studies.

Nature (doesn’t) know best

A common assumption is that nature knows best and interventions to slow down or reverse aging equal tampering with it, which is bad in its own right and therefore shouldn’t be done. This position is apparent in the following quotes from the studies:

“It seems totally unnatural. It seems to be upsetting the natural sequence of things. […] But I think doubling life would be… I don’t like it at all.”

“[…] it’s just not natural to live to 150.”

Quite frankly, this is the kind of teaching you would expect to find in an episode of “The Smurfs”, in which Mother Nature is a sweet old lady with a magic wand and has designed the world to work in a certain way for everyone’s good. However, nature is really just a label used to indicate many things—the interactions between fundamental particles, animal behavior, the intricacies of biochemistry, green foliage, and black holes. No one sat down and decided how long each species should live, and most definitely not for anyone’s good.

Counterexamples of natural things that are bad for you and “unnatural” things that are good for you are plentiful, but we’re not going into counterarguments and confutations; what is interesting to note is that the naturalness argument is presented without further justification: it’s unnatural, hence it’s bad. The interviewees themselves don’t seem to know why it’s bad. It’s rather dangerous to assume that nature knows best when, in fact, it knows nothing at all. Nature does all it does rather well—who wouldn’t, after billions of years of practice—but that’s not necessarily what is best for you.

Another interesting claim is that extending our lifespans would make us less human—as if living around 80 or 90 were a defining quality of humanity:

“To change lifespan that much just seems like, I don’t know, we’re not human anymore… Think of all the intervention we’d need… we’d be counteracting everything about us to make us live longer.”

“[…] it’s kind of inhuman to live a long time, as we are not made that way […]”

It’s honestly difficult to imagine why a lifespan change from around 80 to around 150 would make us any less human than the one from about 40 to about 80 did. However, the covert assumption here might be that extending lifespan would necessarily require radical alterations that would turn us into something we don’t like—a rather stale teaching that has been reiterated, unproven and unchallenged time and again in all manner of fiction, so it wouldn’t be surprising if it had made its way into people’s most deeply held beliefs.

Some interviewees expressed the conviction that curing disease and extending lifespan are fundamentally different:

“There’s a difference between just treating an injury or an illness compared to ‘I’m going to break natural bounds and extend my life’.”

“I don’t think life extension, in the sense of strong life extension, is a necessary thing. Whereas a lot of other aspects of medicine involve fixing things to enable people to live a normal life in a regular lifespan.”

The misconception that might be behind this is that there’s a “right” kind of death—death by old age—whereas other kinds of “early” death, however they may happen, are “bad” kinds of death in that they’re not the way things are supposed to go. It’s almost as if there were a belief that death is scheduled to happen to us irrespective of our health at some point around age 80 or so; death “ahead of schedule” is considered a tragedy, and postponing your “scheduled death” is considered “breaking natural bounds”.

However, this is at odds with everything we know about the functioning of the human body. Medicine is not meant to fix things so that you live a normal life in a regular lifespan; medicine is meant to fix things so that you retain your health and thus continue living. That’s all there is to it. Nowhere is it said that medicine works or should work only within the boundaries of a “regular lifespan”; the only reason why the current “regular” lifespan is of about 80 years is that, thus far, we haven’t been able to cure the ailments that manifest at that age, in pretty much the same way that 300 years ago, we didn’t know how to cure infectious diseases. This interviewee summed it up rather well:

“I don’t know how to separate the rate of aging though from a disease. I don’t know what the difference would be if you took away all of the diseases, if you took away all of the things that could cause heart failure, cancer and all of those sorts of things. I see them the same as aging.”

The authors of the papers reiterated many times how interviewees were favorable to what they perceived as therapies to cure diseases and against all that they perceived as an enhancement; for some reason, extending lifespan was perceived as the latter, rather than merely the obvious consequence of curing the diseases of old age. In this sense, rejuvenation therapies are no more an “enhancement” than any therapy that prevents or cures life-threatening diseases earlier on in life. This point can never be stressed enough.

Discriminations and impositions  

Another extremely common concern is the ill-famed spectre of unequal access to rejuvenation biotechnology, summed up by these two quotes from the studies:

“I don’t think any good will come out of it. It would be beneficial to only one class, supporting only one social class. In a way, we will unbalance the powers.”

“We end up with this society where the poor live their brief little lives and then you know… The rich live forever and have time to accumulate vast resources and there is never any way to cross the divide.”

If you are interested in more detailed counterarguments, you will find them here and here; what is most interesting to note in this venue is the fatalistic attitude of this stance. Not only did interviewees—along with many more people—assume that the dystopian scenario they presented will certainly occur; they didn’t seem to think that measures could be taken to prevent it or even just mitigate its effects or shorten its duration. They didn’t seem to think that the benefits of an aging-free world—which several interviewees acknowledged and which you can read about here, here, and here—might be worth the effort of looking into ways to prevent or mitigate any potential problems, such as inequality of access.

The same can be said of two more common concerns: overpopulation and lack of resources. The answers of the interviewees betrayed the assumption that the problem is inevitable and impossible to even alleviate, as if our technological development had already reached a peak and further innovation in terms of resource production and management were utterly out of the question, neglecting the obvious precedents in this regard—the Malthusian catastrophe has been predicted time and again and always failed to materialize; supporting a world population of even just a billion would have seemed impossible with the technology of 300 years ago, yet present-day technology allows us to cope with seven billion people—not perfectly, but we’re on our way there.

Worse still, interviewees didn’t seem to realize the even more obvious fact that, assuming that rejuvenation would be only for the rich, banning it, as some suggested, would do exactly nothing to narrow the rich-poor divide; at best, it would prevent it from getting larger. However, nobody benefits from a technology not existing, let alone the poor. Imagine if, back in the day when sewers to separate waste from water were first invented, someone suggested that we don’t build sewers anywhere at all because some areas could end up being unjustly left out. Making sure that sewers reach everywhere, even if it takes a long while before they actually do, is a much better idea than having water mixed with waste everywhere forever.

Whether or not the rich live forever is rather inconsequential for the poor, especially as long as they don’t even have the basics covered—even though some people think that the poor somehow find comfort in thinking that one day the rich will die of aging if nothing else gets them first. The idea of relishing someone else’s death, regardless of the circumstances, is so appalling that it’s paradoxical how this whole argument is often called one of “ethics”.

Another interesting concern related to financial possibilities is that if you live longer, you need to support yourself for longer; some interviewees were afraid that the quality of their extended life wouldn’t be good, because their finances might not be good either. This is another scenario where utter pessimism somehow managed to take the place of common sense. It’s very sensible to be afraid of a life of poverty, but if you found yourself so poor at age 30 that your quality of life suffered significantly, the odds are that you’d do your best to try to lift yourself out of poverty well before even contemplating death as a liberation. If you found yourself poor at, say, age 120, and assuming that you were perfectly healthy because of the very life-extension technologies that allowed you to reach that age, why should this case be any different?

At least for some interviewees, the difference might be that they found the prospect of having to work for longer as a “significant downside to taking life-extension pills”. To put it bluntly, they’d consider dying as an alternative to working for longer, which hints that the problem might lie in the jobs they do rather than in how long their lives are.

More concerns related to access to the therapy, rather the opposite of each other, were expressed by interviewees afraid that they might be coerced into using life extension or that life extension users might end up having to watch as their friends and relatives who refuse these treatments slowly wither and die.

For the first concern, this might betray a lack of understanding of what life extension is, because it’s hard to imagine how anyone could worry about being coerced into being healthy; as for the second one, it’s surprising how these interviewees didn’t notice that their fears are already taking place here and now. The old people of today need to get used to the fact that their lifelong friends and companions keep dying around them, and to add insult to injury, their own health is also going critical. Granted, if you yourself die of old age at some point, you won’t have to continue witnessing the death of your loved ones; however, this is pretty much equivalent to curing the disease by killing the patient.

The Real Problems™ are others

The argument that there are higher-priority problems than aging was also among those touched upon by the interviewees:

“I don’t see the point in developing something else at great expense that may not be available to everybody, when money could be channeled towards getting the basics of what people would have a right to them now so that they’re not starving and dying.”

“What’s the point of me living to 150 if six-year-olds are going blind and needing kidney transplants because they’ve got diabetes?”

Appeal to worse problems is very much the fallacy being committed here; once more, the truly important thing is assumed to be something else. For some reason, the interviewees appeared blind to the possibility that the pursuit of rejuvenation might not necessarily be incompatible with that of alleviating poverty, etc; their unproven assumption seems to be that, with the resources available, it is absolutely impossible to achieve both. Also, interviewees didn’t seem to value the life of elderly people as much as that of people who are in danger of death from other causes, such as starvation or health problems at a younger age. In both cases, somebody’s life is at stake, and yet it appears that the life of someone who has already been around for several decades is less worth saving—even though, given the premise of the study, this life wouldn’t end in a handful of years spent in ill health but rather in a far longer period spent in good health.

For some other interviewees, “medicine” was ironically a more important priority than life extension—as if there were any difference between the two. In their minds, the risk is sometimes that research funds could be diverted away from more pressing medical needs. The fact that some of them failed to realize the connection between aging and disease is apparent from this quote:

“They’ve got to look at this [life extension] one hundred years in the future when they’ve got all the diseases sorted out.”

It appears this interviewee expected that, in a hundred years, when all diseases will have been sorted out, people in their 80s will still drop dead for no apparent reason; only then should we start looking into how to extend life. This betrays a serious lack of understanding of the deep connection between healthspan and lifespan, and it is something that advocates of life extension need to make extremely clear. Indeed, the idea that being old equals being sick is (rightfully) so ingrained in our minds that, even though the researchers had clearly stated that life extension means being healthy for longer, some interviewees still struggled to comprehend this and were concerned about how physically and mentally healthy they could be nearing 150 years of age.

Yet some others understood all too well how life extension implies retaining your health during old age, and this was their very concern:

“You’d miss out on that aspect of what it is to be an older person… I think that there’s natural progressions [sic] in growth and that’s why I don’t think you can do it without aging in some ways because you’re not actually physically or whatever in that situation. Intellectually it’s not the same as experience of it. So it’s a whole barraging process that could actually stunt our development; the depth of who we are as human beings.”

This is by far the weirdest concern you’re likely to run into—it’s like saying you shouldn’t cure cancer if you get it, lest missing out on what it is to be an oncological patient. Not all experiences are worth having; from my middle school days, I recall how being hit by a basketball kicked straight into my groin at point-blank range was something I would gladly have done without, and the lack of this experience would hardly have stunted my development—if anything, my early teenage development risked being arrested altogether because of this very experience.

What’s absolutely puzzling about this quote is the kind of development we’re even talking about. A person in his or her 80s has been developing for quite some time already, and intellectually, his or her experience of life is hardly going to be improved by cancer, diabetes, or Alzheimer’s. Besides, whatever experience you might gain by going through the ordeal of age-related diseases, you’re not going to take it with you for very long, so it’s unclear how it would benefit you in the first place. Possibly, the point this person was trying to make might be that you need to experience bad things to learn that they’re bad, but this is true only to an extent. After a certain point in your development, you can extrapolate how good or bad something is without actually experiencing it—believe me, I didn’t need to be hit by that basketball to know that it would have hurt very much.

Old inside

Some interviewees were worried that, rejuvenation or not, an old person always stays old mentally; they feared that they might end up being “an old person in a young person’s world”. This suggests that some people may have internalized the stereotype of old people as being out of touch with the world simply by virtue of being old when, in fact, their health plays a central role in how able they are to stay connected with the rest of us. Old people in today’s collective imagination are confused by computers and technology, less educated than young people, and less open to change and novelty. This depiction is partly correct due to the exceptionally large generational gap between our generation and our grandparents’—in some cases, even our parents’. It is conceivable that, having been exposed to this representation of the elderly our whole lives, some of us conclude that we, too, will be like this in our old age, as if this way of being were a product of the age itself rather than the sociocultural context in which we spent our lives.

Gerontocratic scenarios

Some interviewees showed another typical concern—that the older, rejuvenated people might just keep consolidating their wealth and power, shutting out younger people from opportunities. The long-lived elderly, they feared, might also hinder generational turnover and the emergence of new ideas.

An important factor that interviewees didn’t seem to think about is that being part of a new generation doesn’t automatically make you able to have new or better ideas. However young or smart you may be, you will have a hard time being much of an innovator if you don’t have access to adequate education and aren’t encouraged to engage in open, creative thought. Creativity and new ideas need these elements to thrive; they don’t just magically appear with the turn of every generation. Naturally, the gradual loss of brain plasticity as we age may make it harder for older people to be innovative, but if this problem can be fixed by sufficiently comprehensive rejuvenation therapies, then there’s no reason to assume that long-lived elderly will be a drag on progress.

As for the concern of a gerontocratic elite taking over as a consequence of rejuvenation, one should notice above all that it is typically expressed in such a vague fashion that it is impossible to falsify. Nothing absolutely prevents any dystopia from ever coming into being; in order to be able to tell whether rejuvenation will lead to a gerontocracy in 300 years, we would need information on the socioeconomic and technological context of the coming three centuries. Without it, this concern is pure fear-driven speculation. Its profound appeal to people’s sense of justice is probably what allows it to bypass rational scrutiny and appear as a valid objection despite the lack of evidence.

Ethics

According to the study’s authors, some participants defined “being ethical” as “thinking beyond one’s own life”; in their view, life extension didn’t fulfill this criterion and was an unethical, selfish pursuit:

“Ultimately, I don’t know if everyone should be doing it, but you know how you have those selfish desires?”

Life extension is about eliminating useless suffering just as much as the rest of medicine. Doctors saving people from deadly diseases are thinking well beyond their own lives, and it’s unclear why this wouldn’t be the case if they saved lives by administering rejuvenation treatments.

Other interviewees were instead clear that life extension is perfectly ethical:

“I can’t see an ethical issue. There’s no more an ethical issue than medicine being able to cope with disease. Is there an ethical issue in that? They’re prolonging life now with immunization and even heart transplants. People have come to accept this now.”

Others suggested that opposing life extension is unethical, because

“[…] you’re killing people. If you have the world where you can take an action where you do make someone live longer, or you can take the action that you can say ‘live shorter’, which is a take no action at all, that’s still an action. Then you’re killing them, you caused their death. Your action of not doing anything causes their death. So it’s unethical to not do this.”

The belief that life extension is a selfish pursuit was further stressed in other interviews:

“But then you’ve got all the societal impacts like cost and population growth. There are so many different things that nobody really thinks about when they’re thinking ‘Oh, I could live to 200, that sounds great.’”

“They [people who want life extension for themselves] are not thinking about anyone else.”

Once more, interviewees took the dire consequences they imagined for granted. As the study authors themselves pointed out, to some interviewees, the potential downsides of life extension appeared to be such inescapable certainties that they were not interested in the possibility at all. This might explain the belief that life extensionists don’t think about anyone else; seeing the “selfish” benefit of prolonging your healthy lifespan is easy, but it’s far harder to see that the alleged societal costs of it are not as set in stone as one might think.

One last, interesting position on the selfishness of life extension was expressed by the following interviewee:

“I don’t think there’d be any great social benefits in me living to 300… It’s all about greed and selfish purposes I suppose for why you would try to prolong your life. Ultimately, I don’t think it would impact the world in a positive way. It’s fair to say I wouldn’t be doing it for social reasons.”

It is again apparent that what really matters is not individual people’s lives—only what is good for society matters. However, society has no point if not that of serving the individuals of which it is comprised; if society asks its members to die for society’s sake, it is not doing them a very good service.

In reality, human society doesn’t have much to gain from shorter lifespans for its members, and its functioning is unlikely to be hindered by life extension. Aspects of it will certainly require rethinking, but it is indeed constant rethinking of how society works that allows us to improve it.

Fear of death

To some interviewees, fear of death wasn’t a good enough reason to justify life extension:

“Yes, it’s selfish… but it depends on what reasons you want to do it… they shouldn’t be able to extend their life just because they’re afraid of dying. It should be for a greater cause.”

The idea that only a “greater cause” than fearing for your own life legitimizes use of life extension is reminiscent of the old ideal that your life only matters as long as it serves the rest of society in some way. (The “greater cause” can’t be much else than serving others, if life extension for your own sake is not allowed.)

The ancient idea that death must not be feared—in part to exorcise the fear, very strong indeed, that it instills, and in part because a fearless army was in the best interest of the rulers of the past—has made its way into our modern time and is still alive and well. Being afraid of death is still mostly seen as a shameful thing, and many people still proudly proclaim that they don’t fear it; they’re much more afraid of the horrors that, allegedly, are an inevitable consequence of longer, healthier lives. Among the study participants who acknowledged the benefits of life extension, very few mentioned allaying the fear of death as a good reason; it wouldn’t be surprising in the least if they didn’t because they thought that it would be shameful to do otherwise.

Still, if we really weren’t afraid of death, our languages wouldn’t be full of all manner of euphemisms, edulcorations, and embellishments for it; religions wouldn’t all be hinging on overcoming death through resurrection, reincarnation, and the like; we wouldn’t have come up with any of the technologies that allow us to save lives in the most desperate cases; and we wouldn’t consider it heroic to save other people’s lives even at the cost of endangering our own.

Conclusion

Some of the most common concerns involving life extension are often taken to be inevitable consequences of it; from what can be seen in the two studies, interviewees never doubted that their fears would materialize if life extension were ever achieved. It would be interesting, as well as useful for more effective advocacy, to establish whether this happens because of a lack of relevant knowledge, the psychological effects of our perception of aging, or a combination of both.

Literature

[1] Partridge, B., Underwood, M., Lucke, J., Bartlett, H., & Hall, W. (2009). Ethical concerns in the community about technologies to extend human life span. The American Journal of Bioethics, 9(12), 68-76.

[2] Partridge, B., Lucke, J., Bartlett, H., & Hall, W. (2009). Ethical, social, and personal implications of extended human lifespan identified by members of the public. Rejuvenation research, 12(5), 351-357.

Nicola Bagalà is a bit of a jack of all trades—a holder of an M.Sc. 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.

Citi Lists Anti-Aging Medicines in Top 10 Disruptive Technologies – Article by Steve Hill

Citi Lists Anti-Aging Medicines in Top 10 Disruptive Technologies – 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 August 30th, 2018. In this article, Mr. Hill presents Citi’s latest disruptive innovation publication, in which anti-aging medicine is #2 on the list! This is one more example, out of the myriad of examples, of how big of an impact this field is making. One of the reasons Citi considers the development of anti-aging medicines to have a high impact is the fact that “U.S. health spending, which increases significantly with age in concordance with age-related diseases, is expected to exceed ~20% of U.S. gross domestic product (GDP) by 2025.” 

~Bobby Ridge, Assistant Editor, June 27, 2019

Citi has produced another of its Disruptive Innovations publications, which takes a look at what it considers to be the top ten disruptive technologies. It is a sign of the changing times that anti-aging medicines are number 2 in its list.

1. All-Solid-State Batteries
2. Anti-Aging Medicines
3. Autonomous Vehicle Networks
4. Big Data & Healthcare
5. Dynamic Spectrum Access
6. eSports
7. 5G Technology
8. Floating Offshore Wind Farms
9. Real Estate Market Disruptors
10. Smart Voice-Activated Assistants

What was considered fringe science a decade ago is now rapidly becoming a mainstream industry. Our understanding of aging has advanced quickly in the last 10 years, and the tools and innovations seem to come more quickly with each passing year. A variety of therapies that target different aging processes are in development, and some are at fairly advanced stages; if you are interested in their progress, check out the Rejuvenation Roadmap.

Advancing Health by Turning Back Time

The legend of the restorative powers of the Fountain of Youth has fascinated human civilization throughout the generations, dating all the way back to the Greeks (e.g., Herodotus). Other hypothetical conduits for a return to a state of youthfulness (e.g. the Philosopher’s Stone) have featured prominently throughout human civilization as alluring, but equally elusive. Fast forward to 2018, and very recent cutting-edge scientific breakthroughs may, at long last, fundamentally explain why we age. This rapid scientific progress could spawn FDA-approved therapeutics potentially in the next decade, with the primary goal of keeping us younger and alive for longer.

Today, the anti-aging market, while huge (~$200 billion globally), is largely restricted to non-therapeutics (cosmetic products and procedures). At the same time, U.S. health spending, which increases significantly with age in concordance with age-related diseases (see Figure 8), is expected to exceed ~20% of U.S. gross domestic product (GDP) by 2025. Thus, with scientific breakthroughs emerging this decade on the cellular origins of why the tissues in our body’s age, novel anti-aging medicines may become one of the next big disruptions in the healthcare market.

Senolytics are the main focus here, which is logical given that, of all the therapies being developed to combat aging, they are the farthest along in the pipeline. These analysts suggest that we could see senolytics arrive by 2023; while these drugs are only part of the full suite of therapies required to bring aging under medical control, it is likely that we will see senolytics and, perhaps, a few other therapies arrive at that time.

First Senolytic Therapy Could Be Approved by 2023

The first senolytic therapy in clinical trials is a compound by Unity, UBX0101, which is a small-molecule drug that functions by inducing apoptosis (i.e., programmed cell death), specifically in senescent cells. The company is first testing UBX0101 locally in patients with moderate osteoarthritis of the knee, which is a substantially large market (~17 million patients). Initial proof-of-concept data from the Phase 1 trial are expected in the first quarter of 2019. If successful in later clinical development through Phase 3, UBX0101 could become commercially available by 2023.

While speculative given the novelty of the senolytic therapeutic strategy, a successful therapeutic that could resolve osteoarthritic knees and return knee tissue to a more youthful state could have a negative impact on the knee-replacement surgery market (currently projected to grow to >3 million knee replacements per year by 2030). Because other senolytics are being developed for multiple
ophthalmologic (wet AMD, glaucoma, diabetic retinopathy) and pulmonary (COPD, idiopathic pulmonary disease) indications, within the next ~10–20 years patients with a range of age-related diseases may experience a decreased need for therapies now considered standard of care.

UNITY, Siwa, and Oisin are all mentioned in the report. and it is worth having a read, as the section about aging is fairly large and detailed and takes a look at past and present attempts to combat age-related diseases by targeting the aging processes directly.

Conclusion

It is beyond question that progress and interest in the field is growing quickly, and with some therapies now entering human trials, we could be close to a societal tipping point at which more people start to take notice of the potential of new medical approaches. There is a long way to go before we can end age-related diseases, but the tide has turned.

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.

 

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.

The Importance of an “Industrial Space Elevator” to Transhumanism and the “Futurist New Deal” Platform – Article by Nikolay Agapov

The Importance of an “Industrial Space Elevator” to Transhumanism and the “Futurist New Deal” Platform – Article by Nikolay Agapov

Nikolay Agapov


Editor’s Note: The U.S. Transhumanist Party / Transhuman Party (USTP) publishes this article by Nikolay Agapov to advance the goals of Section XVII of the USTP Platform, which states that “The United States Transhumanist Party holds that present and future societies should take all reasonable measures to embrace and fund space travel, not only for the spirit of adventure and to gain knowledge by exploring the universe, but as an ultimate safeguard to its citizens and transhumanity should planet Earth become uninhabitable or be destroyed.” The construction of a highly economical infrastructure project such as the Agapov Orbital Lift would greatly reduce the costs of space travel and thus enable rapid exploration and development of space for the benefit of humankind and all sentient entities – thus also accelerating our transition into the next era of our civilization. As of this time, the USTP has not yet endorsed a Presidential candidate but welcomes activity from all of our Presidential Primary candidates to advance the USTP Platform. 

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party / Transhuman Party, June 23, 2019


This article is primarily about  the value to society of an industrial space elevator; which I believe could have already been built using a small fraction of the resources that have been spent on space tourism for a select few individuals.  But before we begin, I would like to take a moment to talk about how “Space Age” goals do correlate quite strongly with the goals of “Digital Democracy” and the strengthening of your middle class more generally, that are described in Mr. Johannon Ben Zion’s “Futurist New Deal” platform as a candidate seeking the Presidential nomination of the Transhumanist Party.  I have been previously described in an interview for this site as an “Open-Source Business Developer,” a term which is not a direct translation of the phrase that I used in the Russian interview, but it does describe this underlying commonality fairly well. By using “network technology” and allowing a larger group of peers to participate in the space industry, we’ll create a system that is making better use of the funds and resources that it has allocated and perhaps more importantly, one that can and will evolve as a matter of course to serve humankind.  

This open yet technocratic principle is also very well understood when it comes to more decentralized and more representative forms of government, and the funding of social programs that support the middle class, whether they are funded in the present day by largely public means or in the near-future by public-private partnerships.  

In a great many economies with post-industrial elements including Russia – although it is quite far from the strongest of economies – it is widely believed that the birth rate is “dangerously low.”  So much so that future generations of adults, working people, are said to have to provide for far too many retirees – the idea being that this can lead to an economic crisis. To avoid the crisis of an aging population, developed economies are actively attempting to assist young families.  In particular, the Russian government has provided many types of additional social services to young families that are not so widely available in the United States – for example, “Family Paid Leave”, “Universal Healthcare Services”, and other measures designed to encourage these vital family activities.  

I believe that concerns about “under-population” are not entirely rooted in reality; the main problem that people who fear this population bust express is that the population of older people or pensioners, is becoming much larger than the population of young people, and while in 20th-century technology terms that would lead to a shortage of labor, we now live in the 21st century.  Their fears do not take into account the ways in which all of our societies are moving towards full automation; a circumstance that is negating and will continue to negate these generational problems. However, the larger spirit and implementation of this partly fear-based set of policies is correct. Society and the economy flourish when people are free in their time and resources to pursue family life and small businesses; and these things are very strongly represented in the economic policies of the “Futurist New Deal”.

In Russia, the government is also concerned about a lack of human development and lower productivity.  At a recent open press conference, the Russian president announced a program for a sharp increase in overall labor productivity.  Achieving this rapid growth in production is possible only through a massive influx of small, private enterprises, but they must have a high level of automation and be able to quickly recoup the funds invested in them and develop rapidly both in quantitative and qualitative terms.  For this industries-wide sea-change to occur, you first need to create a conducive environment for all entrepreneurs. A democratization of laws and government is necessary for this purpose; but the Russian government in some ways continues to follow a strategy of rigid central planning and economic development through large state projects that have a high price and long implementation periods; this failing itself tends to make these modernization programs which are occurring under government control a rather dubious institution.

At the same time, Russia has a weak civil society and relatively low economic literacy, which do not foster developing entrepreneurial communities at the grassroots level – those not dependent on the government.  I think that developing decentralized production in Russia, as well as in many developing countries, is easier through collaboration with innovators in the United States. The first networks of decentralized industry are more likely to appear in the United States, Western Europe, and China.  After that, they will begin to transfer the rights to use their intellectual property worldwide, for a percentage of the profits. This is similar to the way 20th-century franchises have tended to work.  

Beginning to make these barest kinds of preparations for the economic health of a society, it is not so dissimilar from focusing on better and more discrete goals in the world of near-earth development.  Just as moving away from the rhetoric of “austerity” or nationalism allows you to identify problem areas more clearly, and correct them; the colonization of space by more collaborative efforts on the part of users – with more industrial and less fanciful goals in mind – will be a truly great boon to humankind.

I have begun to create social networks such as my “People of the Space-Era” and various working groups to this end; and I hope that the people of the U.S. Transhumanist Party, perhaps one of the most technologically literate cohorts in the world, will see and promote the value of this “open-source” approach.

Imagine if a new continent here on Earth were discovered and, rather than create trade networks  with that continent, those responsible for dealings with this new land opted to take a lot of “selfies” there instead – and do little else. As the public, you might rightly ask yourselves when it would be an appropriate time to begin to engage in more practical expeditions.  The simple fact is that an information society, any post-industrial society should be making better use of our connectivity and our technology than we are.

 When the first flights into space began, people enthusiastically waited for the first experiments to be followed up by larger-scale developments or innovations, such as those aimed at the practical and permanent venture into space by our species; and all the while hoping for inexpensive reusable rockets, or these fundamentally different ”rocketless” means of space transport to be developed. They waited with bated breath for the first extraterrestrial technological centers to be built, and after them the first extraterrestrial industrial enterprises should have surely followed.  People waited for humanity to start taking real steps towards becoming a space civilization. Sadly the nation-states concerned used their astronauts only to maintain their standing in public opinion, and these state space programs remained at an earlier stage of research and experimentation.

If our society wants to move into the Space Age, it is time for all of us to take the initiative. Team up to work on new global programs such as the development of new industries based on digital production, consisting of miniature factories capable of making their own replacements to accelerate industrial growth on Earth.  And later, in space, such micro-factories will themselves “multiply”, and build an array of near-earth industrial infrastructure, without the onerous costs associated with high-speed travel, operating on principles of development and economic efficiency. Today it is possible to develop on Earth the beginnings of a society on a truly cosmic scale, through the tenacity of many of you space-travel-minded people. These ways of thinking and ultimately this way of life must be adapted to the conditions of a functional space civilization, not tailored to narrower nationalistic or “creative” ends. The most innovative supporters of space expansion must take on these roles as coordinators to create earth-based industrial and entrepreneurial networks vital to this development of new programs for the industrialization of space.

Such initiative would lead to far broader and more robust sets of satellites which would improve the experiences of today’s device and IOT (Internet of Things) users and revolutionize this sadly untapped field of solar energy – which is inexhaustible and eco-friendly.  The development of cosmic mineral resources, the most valuable of these being precious metals and rare earth elements will be supplied to earth with ease. Perhaps of less value, but still market-changing, those many resources that serve in the construction of consumer orbital enterprises and transport systems, and of course the more widespread industrial use of 3-D printing, minimizing the need for expensive cargo delivery from the ground, will become more commonplace in near-earth and earthbound building.

It is indeed possible to suppose that a decentralized civil society which is still overseen by “good-faith” public coordinators could also actively prepare better for the colonization of space than we are preparing today.  For this to happen, the participation of nation-states directly is not needed, and even large capital investments would not be absolutely required; the network world of agile “citizen scientists” itself will become the best source of capital and resources. We need only initiative and personal energy to move past these 20th-century constraints.

One of the projects of these new  rocketless transport systems, which I propose that we implement, is the “Agapov Orbital Lift” (A.O.L.).   The A.O.L. is a simplified version of the space elevator which will remain in geosynchronous orbit but  will not be secured to the ground by a tether. This design is relied upon, as it is far more effective than the “Stationary Space Elevator” which has a cable that reaches the earth.  For the A.O.L. to work, there is a need for some rocketry, as the lower end of the cable will fly above the ground at a height of low orbit, but at a speed below the earth escape velocity of today’s rockets, at 1 – 3 kilometers per second. The A.O.L, unlike competitor lifts, will be able to immediately give us tremendous breakthroughs in the modernization of space transport.  This project is technically feasible since the earth connection cable is not needed, and so additional materials science innovations such as nanotubes or graphene tape need not be made a contingency of the first-generation A.O.L. Suffice it to say that materials such as carbon fiber, “Kevlar,” “Vectran,” or other polyethylene materials of a high degree of polymerization will be strong enough to suit these ends.  These existing materials-science innovations are already wholly mastered by industrial producers, are widely commercially available, and have a cost that is not exorbitantly high for near-earth development.

Waiting for one particular breakthrough is just not worth it when high-strength materials of many kinds are constantly being produced and improved upon, and as we mentioned at some length in our interview, the A.O.L. will also be upgraded many times in the course of its productive life. At certain intervals, older tethers, battered by space debris, will need to be replaced with newer, stronger, and longer ones made with more durable materials. And so, in the course of operation, the A.O.L. system of lifts will in short order be transformed into a stationary one, an achievement which itself would allow for the complete abandonment of missiles in near-earth travel.

The counterweight to the A.O.L. will be the International Space Station (ISS), as its life as a space-science laboratory comes to an end. And as part of the elevator, the station will be able to continue its multifaceted work in an exciting new capacity as a component of a revolutionary transport system. The ISS as counterweight to the elevator would be an appropriation of 100 billion dollars in existing space infrastructure, and its use will couple state space agencies with private firms in a timeless public-private partnership.  In addition, the ISS as part of the orbital elevator will be able to work as a technological platform for mounting satellites and various useful space objects, from relatively light payloads delivered to it by cables from suborbital flight. In doing so we will be responsible for the beginning of true space production.

In my previous interview with Presidential candidate Johannon Ben Zion, we discussed a figure of between 100 and 500 million dollars for the building of a first-generation, highly-automated industrial space elevator.   I understand that many of your readers are skeptical of this design and these figures, and at the risk of repeating myself from earlier in this article, I will say here again what I did not say in that shorter interview published June 12th, which is that the success of such a project could hinge on the “network effects,” the user-generated efforts in numerous interworking systems of networked organizations which are capable of consolidating the work product of industrial enterprises and small entrepreneurs on earth for the implementation of large-scale programs for the industrialization of space.  We must spearhead this construction ourselves in order to turn the entire world industry into a springboard for the colonization of the solar system and not limit this to individual government agencies or scattered and not fully realized private space firms. In short, on this quality of being “Open-Source”, which is again not the exact wording that I preferred to use in the original Russian interview, that phrasing certainly does get to the heart of the way in which this kind of effort should be different from previous private or public space-faring attempts.

Even in the weeks since that interview was conducted, new discoveries of underground resources on the Moon have been made, I believe that had previous lunar expeditions been more focused on making use of these resources, we would already have the industrial infrastructure between our planet and our Moon to be safely excavating these kinds of materials.

It would be unfair to describe private space industry as unconcerned with these improvements; incredible breakthroughs have been made in recent decades toward streamlining space-faring processes, making them cheaper and cleaner.  That said, I believe that almost all of the people working in this business have a fixation with rockets and an almost total lack of interest in the equally practical transport systems that I have described. If these engineers really believe that the focus of space travel is to stick pretty flags in piles of dirt, or engage in publicity stunts where people who are famous solely for being wealthy celebrate their success by enjoying zero gravity for a few hours – my advice is that they should pursue another line of work because these “accomplishments” are not of such great value as we have been led to believe.

My design for a space elevator is meant to be a transition, using the existing infrastructure now in low-earth orbit to create a lift system capable of slow but steady industrial growth – within 3 to 5 years – using the kinds of robotics that industry has taken for granted for a few decades.  To achieve this some adjustments will need to be made to the International Space Station so that its orbit is better positioned to support this lift system. When you consider the hundred or more billion dollars that have been spent on space stations which are now decommissioned, and I would argue have always been underutilized, the choice not to build a space elevator from them seems to me, frankly, a silly one.  The very important point in this design, which I have already iterated but that was sadly not included in the truncated first interview, is that this spacelift will not reach completely to Earth, and vehicles will be required to shuttle payloads up to that point. But as the cost of operating these vehicles will be much lower – as the high speeds required of rockets today to escape Earth’s gravity will not be necessary, the A.O.L. will nonetheless be of great value to industry.

There is no question in my mind that this tether design, which incorporates a few different interworking ultra-strong polymer blends, all of which are currently in widespread industrial use, will suffice for our materials needs.  And I should point out once again, and it has been said many times before, that by first constructing this industrial lift, we will then very soon be able to build out its infrastructure and create parallel lift structures that will quickly improve industrial, and presumably consumer, uses.

With greater interest after significant return on investment from these industrial undertakings, we will very quickly see that this initial design was well worth the effort. I hope that the lack of focus on space tourism in our first-generation A.O.L. design will be seen by potential investors as an asset to both consumers and industry in the long-term.

It is not just nostalgia for my youth that drives my interest in this repurposing of existing space infrastructure like the International Space Station; we should give the ISS a second life; this is the best way to continue the work begun by those 20th-century visionaries who first sought to propel our civilization beyond our atmosphere. These state-sponsored space administrations and the public-private partnerships which today exist in service to space travel and research are not enough to undertake this repurposing.  We need our “open-source” public efforts to become a kind of popular fascination, like the one seen in the 1950s “space race.” However, even the number of users currently contributing to the SETI app would be an excellent start to collaborative design and build efforts that would benefit our repurposing and tether-building efforts.

Such seeds of public fascination in an enterprise can direct public initiatives, both investment and intellectual capital into enterprises no less interesting and potentially far more vital than the some of the mechanisms of today’s Silicon Valley-style capitalism. Furthermore, this will give us a new arena for the development of information technology businesses in conjunction with these new generations of networks and satellite communications, which will make high-speed Internet far more accessible to the entire planet and will overwhelmingly strengthen the global information space of mankind, moving global civilization ever closer to the realization of a true “noosphere.”

Finally, I would reiterate that the focus on the cost of an industrial space lift should not be on the hundreds of millions of dollars in the initial outlay – but rather on the many trillions of dollars that could be generated by making this bold step. The A.O.L. transport infrastructure will confer great economic effects by the creation of a global industry in near-earth development; and just as on land, where railways and ports do not always bring the largest of profits, yet they do underpin the life of entirely greater industries and regions, so will millions of inhabitants benefit by industries developing out into the many hundreds of billions of dollars.

I hope that you will all leave this conversation with a somewhat clearer idea of the purpose and design of my industrial space lift, the “Agapov Orbital Lift”, and as well will consider endorsing Mr. Ben Zion and the “Futurist New Deal;” I believe that the architects of this plan truly do have your best interests as techno-optimists at heart.

Editor’s Note: The U.S. Transhumanist Party / Transhuman Party (USTP) has not yet, as of this publication, endorsed a candidate for U.S. President. Therefore, the statement in the last sentence above by Mr. Agapov should be considered to be his personal opinion only at this time. Readers can view the profiles of all USTP Presidential Primary candidates and make informed decisions regarding which candidate(s) and which of their proposals to support. 

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.

Meet the Naked Mole-Rat: Impervious to Pain and Cancer, and Lives Ten Times Longer Than It Should – Article by Ewan St. John Smith

Meet the Naked Mole-Rat: Impervious to Pain and Cancer, and Lives Ten Times Longer Than It Should – Article by Ewan St. John Smith

Ewan St. John Smith


Smithsonian’s National Zoo/flickr, CC BY-NC-ND

Ewan St. John Smith, University of Cambridge

The naked mole-rat is perhaps one of the most bizarre beasts on the planet. At first glance, it looks like little more than a cocktail sausage with legs and teeth. But beneath its wrinkly pink skin, this creature’s strange and beautiful biology has me fascinated – so much so that I set up a whole research group devoted to studying them. Largely immune to cancer, impervious to some forms of pain, and seemingly blessed with the elixir of life, you may well owe your life to them one day.

As the name might suggest, naked mole-rats buck the mammalian trend by almost completely lacking hair or fur. Living underground in complex networks of tunnels in East Africa, their thermally stable environment means that a few orientation-aiding bodily hairs and facial whiskers are all they need. Lacking evolutionary pressure to regulate their body temperature, they’re also the only known cold-blooded mammal on the planet.

The way naked mole-rats mate and socially organise is more akin to certain insect species than to mammals. Like some species of bees and ants, naked mole-rats are eusocial, living in 100-strong groups headed by a sole breeding female, the queen. But while insects command their colonies with pheromones, the naked mole-rat queen uses physical aggression to keep their groups digging tunnels, foraging, and defending entrances.

No, this isn’t Star Wars – it’s a naked mole-rat defending a tunnel.
Neil Bromhall/Shutterstock

A key tool for both digging and combat is their teeth. Their incisors are exterior to their lips, so that when they bite through hard soil they don’t get a mouthful of earth each time. Naked mole-rats can also move their lower incisors to manipulate objects, and have a large sensory area of their brains dedicated to their teeth in the same way that hands have dedicated brain space in humans.

The peculiarities of naked mole-rat behaviour are captivating in themselves. However, to most scientists, what makes them really exciting is the potential some of their incredible biology holds for making biomedical breakthroughs.

The naked mole rat’s resistance to cancer, diagnosed in humans every two minutes in the UK alone, is a particular area of focus for researchers. In studying why there are just a few documented cases worldwide in naked mole-rats, scientists are hoping to identify new ways to prevent or treat the deadly disease.

As yet, we’re not exactly sure what gives them their resistance. Some evidence suggests that a key difference in one of the meshwork of substances providing structural and nutritional support to cells prevents them from reproducing uncontrollably. However, others have observed different results, so further investigation is needed.

Not content with just being immune to cancer, naked mole-rats are also impervious to some normally agonising chemical stimuli, such as capsaicin (the substance that makes chilli peppers taste hot) and acid (what gives lemon juice and vinegar their kick). For their acid-insensitivity, researchers are clearer about why. A subtle difference in one particular molecule of the animal’s pain-sensing nerves turns acid into an anaesthetic. That is, rather than stimulating pain-sensing nerves, it actually numbs them – just like an anaesthetic that your dentist administers before the drilling starts. Sadly, this superpower only works with specific chemical stimuli – heat and pressure are just as damaging to them as us.

Scientists are now further studying the naked mole-rat to see whether we might be able to make the human pain system similarly impervious to acid pain. This could be extremely useful for cancer and arthritis sufferers, for whom build-ups of acid in body tissue can be a major contributor to chronic pain. The molecule responsible for insensitivity to acid in mole-rats also plays a role in human genetic conditions that drastically alter pain perception, and as a result of this convergent research, potential painkillers targeting this molecule have made it into clinical trials in humans.

Naked mole-rats are also highly resilient to low oxygen conditions. Their nerve cells can function for almost one hour in the complete absence of oxygen, by instead using fructose to power energy production. In studying this remarkable ability, my lab and others are hoping to uncover novel treatments to prevent brain damage in stroke patients.

Naked mole-rats are also renowned for their longevity. Broadly speaking, a larger body equals longer life in mammals. Standard lab mice weigh around 35 grams, and usually live a maximum of two to three years. Naked mole-rats can be up to twice as heavy, so might be expected to live four to six years, but can actually survive for more than 30 years in captivity. That’s longer than the lifespan of polar bears and giraffes. And while humans experience from many ageing-associated health problems (for example, osteoarthritis), naked mole-rats appear to age without issue. Research into the ageing processes of naked mole-rats is only in its infancy, but could have multiple implications for treating ageing-related conditions in humans.

Newborn naked mole-rats weigh as little as two grams.
belizar/Shutterstock

Naked mole-rats may look comical, but their magical biology is no laughing matter. Studying their hidden powers will not always result in preventions, cures and treatments for human ailments because of fundamental differences between the species. However, every new insight has the potential to lead to a breakthrough – as animal research has continually done throughout recent history. By unlocking the secrets held within their cells in a responsible manner, we may one day improve countless human lives.The Conversation

Ewan St. John Smith, University Senior Lecturer in Pharmacology, University of Cambridge

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Study Shows Telomerase Gene Therapy Does Not Increase Cancer Risk – Article by Steve Hill

Study Shows Telomerase Gene Therapy Does Not Increase Cancer Risk – 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 August 27, 2018. This article takes another step forward toward clearing up a common misconception that many scientists and laypeople hold, i.e., the notion that extending telomeres causes cancer. Mr. Hill cited a recent article published in the journal PLOS Genetics, in which researchers found there to be no increase in cancer, even when telomeres were extended in mice from cancer-prone mouse strains. Hopefully this article will help researchers reevaluate this misconception so this very important age-reversal research will be advanced much faster.

~ Bobby Ridge, Assistant Editor, June 20, 2019

Researchers have demonstrated that telomerase gene therapy does not increase the risk of cancer, even in strains of mice that are particularly susceptible to cancer [1].

A tale of telomeres

Short telomeres trigger cellular senescence and are thought to be one of the primary hallmarks of aging, which has led to various researchers seeking ways to restore the telomeres in order to prevent cells from dying and to encourage division and tissue regeneration. We won’t go over the basics of telomeres and how they influence aging  here, but if you would like to learn more, check out our telomeres article, which explains it all.

Ever since Dr. Maria Blasco and her team at the Spanish National Cancer Research Centre (CNIO) first used telomerase gene therapy in mice back in 2012, a debate has raged about the potential of telomerase for regenerating tissue and reversing some aspects of aging versus the risk of it causing cancer.

Despite the concerns, it has proved effective against infarction by spurring regeneration of cardiac tissue and in treating aplastic anaemia and idiopathic pulmonary fibrosis in mice; all of these conditions are associated with critically short telomeres.

The CNIO’s Telomeres and Telomerase Group, which conducted the new study, has been investigating the potential of using telomerase therapy to treat age-related diseases for many years. Its 2012 publication featured a specially developed gene therapy that used an adeno-associated virus (AAV) to deliver a payload to cells that reactivated the telomerase gene, which can restore lost telomeres by creating the telomerase enzyme, and it appeared to delay and reverse certain aspects of aging [2].

Its AAV therapy is special in that the vectors do not integrate into the genomes of the target cells. Therefore, the telomerase activation only lasts for a few cell cycles before its effects cease. This transient activation of telomerase makes for a safety net, as unlimited cell division is only a step away from cancer.

Abstract

Short and dysfunctional telomeres are sufficient to induce a persistent DNA damage response at chromosome ends, which leads to the induction of senescence and/or apoptosis and to various age-related conditions, including a group of diseases known as “telomere syndromes”, which are provoked by extremely short telomeres owing to germline mutations in telomere genes. This opens the possibility of using telomerase activation as a potential therapeutic strategy to rescue short telomeres both in telomere syndromes and in age-related diseases, in this manner maintaining tissue homeostasis and ameliorating these diseases. In the past, we generated adeno-associated viral vectors carrying the telomerase gene (AAV9-Tert) and shown their therapeutic efficacy in mouse models of cardiac infarct, aplastic anemia, and pulmonary fibrosis. Although we did not observe increased cancer incidence as a consequence of Tert overexpression in any of those models, here we set to test the safety of AAV9-mediated Tert overexpression in the context of a cancer prone mouse model, owing to expression of oncogenic K-ras. As control, we also treated mice with AAV9 vectors carrying a catalytically inactive form of Tert, known to inhibit endogenous telomerase activity. We found that overexpression of Tert does not accelerate the onset or progression of lung carcinomas, even when in the setting of a p53-null background. These findings indicate that telomerase activation by using AAV9-mediated Tert gene therapy has no detectable cancer-prone effects in the context of oncogene-induced mouse tumors.

More support for telomerase gene therapy

Despite this safety measure, the medical use of telomerase therapy has been held back due to concerns of cancer risk, so the researchers at CNIO set out to see if this concern is justified.

To do this, they used this gene therapy in a mouse model that is at high risk of lung cancer. Their results showed that activating the telomerase gene via their gene therapy does not increase the risk of developing cancer, not even in this cancer-prone mouse strain.

These findings suggest that this gene therapy appears to be safe even in a pro-cancer environment. The authors chose this cancer-prone mouse strain to create a “killer experiment”, which creates a worst-case scenario that tests a hypothesis to its limit; if the hypothesis holds true despite the extreme scenario, it shows that the hypothesis is good. Because this therapy did not increase cancer risk in this extremely vulnerable mouse population, it demonstrates that telomerase gene therapy is possibly safe enough to use in humans.

The road ahead

The safety and utility of telomerase therapy is becoming more apparent with each passing year. The purpose of this new study was to demonstrate the plausibility of using telomerase to safely treat many diseases that currently have no cure, such as pulmonary fibrosis, and to help speed up its progress into human clinical trials.

Conclusion

The potential of telomerase gene therapy has long been debated amid cancer concerns, but this experiment suggests that those concerns are unfounded. There is no doubt that telomerase can and does regenerate tissue when it is delivered via gene therapy and that it does reverse various aspects of aging in multiple models.

Can we safely use what some people describe as a double-edged sword and apply it the fight against aging? This experiment strongly suggests that yes, we can.

Literature

[1] Muñoz-Lorente, M. A., Martínez, P., Tejera, Á., Whittemore, K., Moisés-Silva, A. C., Bosch, F., & Blasco, M. A. (2018). AAV9-mediated telomerase activation does not accelerate tumorigenesis in the context of oncogenic K-Ras-induced lung cancer. PLoS genetics, 14(8), e1007562.

[2] de Jesus, B. B., Vera, E., Schneeberger, K., Tejera, A. M., Ayuso, E., Bosch, F., & Blasco, M. A. (2012). Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO molecular medicine, 4(8), 691-704.

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.