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

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

Steve Hill


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

~ Bobby Ridge, Assistant Editor, July 7, 2019


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

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

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

Knowledge is power

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

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

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

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

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

Future-positive

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

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

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

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

Reasons to be cheerful

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

Senolytics

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

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

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

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

Partial cellular reprogramming

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

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

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

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

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

In closing

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

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

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

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

Moving Closer to a Vaccine for Atherosclerosis – Article by Steve Hill

Moving Closer to a Vaccine for Atherosclerosis – 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 April 13, 2018. In this article, Mr. Hill reviews a study published by the La Jolla Institute for Allergy and Immunology, in which the study authors successfully vaccinated atherosclerotic mice. In fact, this method supported Dr. Aubrey de Grey’s early insight – his claim that we must attack plaque altogether.

~ Bobby Ridge, Assistant Editor, July 5, 2019

Scientists could be one step closer to a solution to atherosclerosis by preventing the buildup of plaques that clog the arteries and lead to strokes and heart attacks.

What is atherosclerosis?

Atherosclerosis is the accumulation of cholesterol-containing plaques in the walls of arteries; this causes them to narrow, leading to reduced blood flow, higher blood pressure, and an increased risk of a heart attack or stroke. Atherosclerosis is the number one cause of death globally, and, by far, the highest risk factor for this disease is aging, although there are lifestyle factors, such as poor diet, smoking, obesity, and being sedentary.

Drugs such as statins attempt to manage the symptoms but are not truly effective in combating this disease, as they do not address the underlying cause: the formation of the sticky plaques that clog the arteries. Scientists such as Dr. Aubrey de Grey from the SENS Research Foundation have long been advocating for therapies that remove or prevent the formation of plaques altogether, as this would address the problem directly.

One step closer to a solution

In the journal Circulation, researchers at the La Jolla Institute for Allergy and Immunology have published a new study that supports the possibility that there are ways to prevent the formation of plaques in the first place [1]. The team has reported the successful vaccination of atherosclerotic model mice by using a small piece of protein cut from “bad cholesterol”, which facilitates the formation of plaques.

The vaccine was shown to reduce plaque in the mice, and the team also identified the T cells most likely responsible for positive outcomes in human blood samples as part of the same study. The researchers suggest that this technique could form the basis of a vaccine for people.

The vaccine works by boosting the activity and numbers of a type of T cell responsible for reducing inflammation, which leads to a reduction of plaque formation. We have talked about therapies that modulate the immune system and change the ratio of immune cells multiple times, and it is looking like an increasingly promising avenue of research.

“Bad cholesterol” is an amalgam of cholesterol, which is a lipid, and its carrier, low-density lipoprotein (LDL). In order to create the vaccine, the team engineered a peptide that represents a short section of LDL.

The team mounted this peptide on a scaffold called a tetramer and exposed it to immune cells to see which ones became activated in its presence. They tested human blood from two groups of women, one with plaques and one without, to see which immune cells responded to the presence of the peptide.

They observed that a type of regulatory T cell (Tregs) was activated in both groups, although the numbers of Tregs was much lower in subjects with plaques than subjects without, as were the presence of other types of T cells. This suggests that the function of Tregs is somehow hampered by the inflammation that atherosclerosis causes.

The next generation of vaccines that offer greater utility

As well as having the potential to address atherosclerosis, this research spotlights the utility of next-generation vaccines. The immunogenic component of traditional vaccines is a cocktail of molecules harvested from dead or weakened pathogens, but this approach does not work against non-infectious diseases like cancer and atherosclerosis; these next-generation vaccines are much more specific, as they can regulate the immune response using just a single peptide. This means vaccines that target non-infectious diseases are now possible, and, as they are highly targeted, they should have fewer unwanted side effects.

The results presented in this paper show that an effective vaccine against atherosclerosis is now potentially possible. However, the researchers do caution that there is more research to be done before this vaccine can be translated to human use.

Conclusion

While statins simply try to treat the symptoms, a therapy that prevents the buildup of plaques in the first place would be a very welcome step in the battle against age-related diseases and the suffering they bring. If the therapy can be translated to people, it would make strokes and heart attacks practically a thing of the past, and that day cannot come soon enough.

Literature

[1] Kimura, T., Kobiyama, K., Winkels, H., Tse, K., Miller, J., Vassallo, M., … & Jenkins, M. K. (2018). Regulatory CD4+ T Cells Recognize MHC-II-Restricted Peptide Epitopes of Apolipoprotein B. Circulation, CIRCULATIONAHA-117.

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.

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

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

Steve Hill


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

~ Bobby Ridge, Assistant Editor, June 29, 2019

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

Why this will not stop progress

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

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

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

Researchers are free to target aging processes

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

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

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

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

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

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

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

This does not mean regulatory changes are not needed

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

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

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

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

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

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

Moving with the times

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

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

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

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

Conclusion

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

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

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

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

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

Reason
Nicola Bagalà


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

~Bobby Ridge, Assistant Editor, June 25, 2019

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

What is your take-home message for our readers?

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

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

Dr. Aubrey de Grey Accelerates His Estimates – Article by Steve Hill

Dr. Aubrey de Grey Accelerates His Estimates – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill highlights a recent webinar where Dr. Aubrey de Grey, the Biogerontology Advisor of the U.S. Transhumanist Party / Transhuman Party, revised his projections for the arrival of rejuvenation treatments in a more optimistic direction. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party / Transhuman Party, April 16, 2019


On January 28, 2019, we held a webinar with the SENS Research Foundation as part of a new ongoing series of research webinars. During the webinar, we asked Dr. Aubrey de Grey how close we might be to achieving robust mouse rejuvenation (RMR) and robust human rejuvenation, and his answer was somewhat surprising.

RMR is defined as reproducibly trebling the remaining lifespan of naturally long-lived (~3 years average lifespan) mice with therapies begun when they are already two years old.

Dr. de Grey now suggests that there is a 50/50 chance of achieving robust mouse rejuvenation within 3 years from now; recent interviews and conversation reveal that he’d adjusted this figure down from 5-6 years. He has also moved his estimation of this to arrive from around 20 years to 18 years for humans.

So, what is the basis for this advance in schedule? Dr. de Grey is more optimistic about how soon we might see these technologies arrive, as the level of crosstalk between damages appears to be higher than he originally anticipated a decade ago. This means that robust mouse and human rejuvenation may be easier than he previously believed.

We also asked Dr. de Grey which of the seven damages of aging was the most challenging to address. Originally, he thought solving cancer through OncoSENS methods was the biggest challenge in ending age-related diseases. However, intriguingly, he speaks about his enthusiasm for immunotherapy and how it may potentially solve the cancer issue and negate the need for Whole-body Interdiction of Lengthening of Telomeres (WILT), which was always considered a last-resort approach to shutting down cancer.

There are two main components of the WILT approach. The first is to delete telomerase-producing genes from as many cells as possible, as human cancers lengthen telomeres through one of two available pathways, and the second is to avoid the harmful consequences of our cells no longer having telomerase by periodically transplanting fresh stem cells, which have also had their telomerase-associated genes knocked out, to replace losses.

This approach has always been considered extreme, and Dr. de Grey has always acknowledged that this was the case. However, over a decade ago when Dr. de Grey and Michael Rae originally proposed this in the book Ending Aging, immunotherapy was simply not on the radar. Now, there are alternatives to WILT that show true potential and less need for radical solutions, and it is reassuring to see that Dr. de Grey is so enthusiastic about them.

He now suggests that MitoSENS is probably the most challenging to tackle of the seven types of damage in the SENS model of aging. This is no surprise given that DNA and mtDNA damage are highly complex issues to fix.

On that note, we asked Dr. Amutha Boominathan from the MitoSENS team which mitochondrial gene was their next target after they had successfully created nuclear copies of the ATP-6 and ATP-8 genes.

MitoSENS will be launching a new fundraising campaign on Lifespan.io later this year with the aim of raising funds to progress to more of the mitochondrial genes. This time, the aim will be to move the approach to an animal model and demonstrate how it could be used to correct mitochondrial defects.

Finally, if you are interested in getting involved directly with these webinars and joining the live audience, check out the Lifespan Heroes page.

About  Steve Hill

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

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

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

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

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

Finally, Rejuvenation is a Thing! – Fresh Interview with Aubrey de Grey by Ariel VA Feinerman

Finally, Rejuvenation is a Thing! – Fresh Interview with Aubrey de Grey by Ariel VA Feinerman

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Ariel VA Feinerman
Aubrey de Grey


This interview was originally published here

Preface

What is ageing? We can define ageing as a process of accumulation of the damage which is just a side-effect of normal metabolism. While researchers still poorly understand how metabolic processes cause damage accumulation, and how accumulated damage causes pathology, the damage itself — the structural difference between old tissue and young tissue — is categorized and understood pretty well. By repairing damage and restoring the previous undamaged — young — state of an organism, we can really rejuvenate it! It sounds very promising, and so it is. And for some types of damage (for example, for senescent cells) it is already proved to work!

Today in our virtual studio, somewhere between cold, rainy Saint-Petersburg and warm, sunny Mountain View, we meet Aubrey de Grey, again! For those of you who are not familiar with him, here is a brief introduction.

Dr Aubrey de Grey is the biomedical gerontologist who researched the idea for and founded SENS Research Foundation. He received his BA in Computer Science and Ph.D. in Biology from the University of Cambridge in 1985 and 2000, respectively. Dr. de Grey is Editor-in-Chief of Rejuvenation Research, is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organizations. In 2011, de Grey inherited roughly $16.5 million on the death of his mother. Of this he assigned $13 million to fund SENS research.

Note: If you have not read “Ending Aging” yet I suggest you to do it as soon as possible, and to be more comfortable with the ideas we are discussing below I highly recommend you to read short introduction to SENS research on their web page. Also if you are interested in recent news and up-to-date reviews about [anti]ageing and rejuvenation research the best place to look for is Fight Aging! blog. Finally, if you are an investor or just curious, I highly encourage you to take a look at Jim Mellon’s book “Juvenescence”.

Interview

Ariel Feinerman: Hello, Dr Aubrey de Grey!

Aubrey de Grey: Hello Ariel — thanks for the interview.

Ariel Feinerman: How do you feel 2018 year? Can you compare 2018 to 2017 or early years? What is changing?

Aubrey de Grey: 2018 was a fantastic year for rejuvenation biotechnology. The main thing that made it special was the explosive growth of the private-sector side of the field — the number of start-up companies, the number of investors, and the scale of investment. Two companies, AgeX Therapeutics and Unity Biotechnology, went public with nine-digit valuations, and a bunch of others are not far behind. Of course this has only been possible because of all the great progress that has been made in the actual science, but one can never predict when that slow, steady progress will reach “critical mass”.

Ariel Feinerman: In 2017 SENS RF have received about $7 million. What has been accomplished in 2018?

Aubrey de Grey: We received almost all of that money right around the end of 2017, in the form of four cryptocurrency donations of $1 million or more, totalling about $6.5 million. We of course realised that this was a one-off windfall, so we didn’t spend it all at once! The main things we have done are to start a major new project at Albert Einstein College of Medicine, focused on stem cell therapy for Alzheimer’s, and to broaden our education initiative to include more senior people. See our website and newsletters for details.

Ariel Feinerman: What breakthroughs of 2018 can you name as the most important by your choice?

Aubrey de Grey: On the science side, well, regarding our funded work I guess I would choose our progress in getting mitochondrial genes to work when relocated to the nucleus. We published a groundbreaking progress report at the end of 2016, but to be honest I was not at all sure that we would be able to build quickly on it. I’m delighted to say that my caution was misplaced, and that we’ve continued to make great advances. The details will be submitted for publication very soon.

Ariel Feinerman: You say that many of rejuvenating therapies will work in clinical trials within five years. Giving that many of them are already working in clinical trials or even in the clinic (like immunotherapiescell and gene therapies) do you mean the first — maybe incomplete — rejuvenation panel, when you speak of early 2020?

Aubrey de Grey: Yes, basically. SENS is a divide-and-conquer approach, so we can view it in three overlapping phases. The first phase is to get the basic concept accepted and moving. The second phase is to get the most challenging components moving. And the third phase is to combine the components. Phase 1 is pretty much done, as you say. Phase 2 is beginning, but it’s at an early stage. Phase 3 will probably not even properly begin for a few more years. That’s why I still think we only have about a 50% chance of getting to longevity escape velocity by 2035 or so.

Ariel Feinerman: Even now many investors are fearful of real regenerative medicine approaches. For example pharmacological companies which use small molecules, like Unity Biotechnology, received more than $300 million, in much more favour than real bioengineering companies like Oisin Biotechnologies, received less than $4 million, even though the biological approach is much more powerful, cheap, effective and safe! Why is this so in your opinion, and when can we see the shift?

Aubrey de Grey: I don’t see a problem there. The big change in mindset that was needed has already occurred: rejuvenation is a thing. It’s natural that small-molecule approaches to rejuvenation will lead the way, because that’s what pharma already knows how to do. Often, that approach will in due course be overtaken by more sophisticated approaches. Sometimes the small molecules will actually work well! It’s all good.

Ariel Feinerman: Do you agree that the small-molecule approach is generally the wrong way in the future rejuvenation therapies? Because they have many flaws — especially their main mechanism via interference with human metabolism. Unlike them SENS bioengineering therapies are designed to be metabolically inert — because they just eliminate the key damage, they do not need to interfere with metabolism, so it is much easier than usual to avoid side effects and interactions with other therapies. They just eliminate the key damage, which means they are easier to develop and test — and much safer.

Aubrey de Grey: Ah, no, that’s too simplistic. It’s not true that small molecules always just “mess with metabolism” whereas genetic and enzymatic approaches eliminate damage. Small molecules that selectively kill senescent cells are absolutely an example of SENS-esque damage repair; the only thing against them is that it may be more difficult to eliminate side-effects, but that’s not because of their mode of action, it’s because of an additional action.

Ariel Feinerman: In recent years many countries gave the green light for regenerative medicine. Fast-track approval in Japan, for example, allows for emerging treatments to be used so long as they have been proven safe. The similar approach works in Russia. What about the EU or USA?

Aubrey de Grey: There’s definitely a long way to go, but the regulatory situation in the West is moving in the right direction. The TAME trial has led the way in articulating an approvable endpoint for clinical trials that is ageing in all but name, and the WHO has found a very well-judged way to incorporate ageing into its classification.

Ariel Feinerman: Do you think of working with USA Army? As far as we know they conduct research on regeneration and are very interested in keeping soldiers healthier for longer. And they have much money!

Aubrey de Grey: The Department of Defense in the USA has certainly funded a lot of high-impact regenerative medicine research for many years. I’m sure they will continue to do so.

Ariel Feinerman: Is any progress in the OncoSENS programme? Have you found any ALT genes? Is any ongoing research in WILT?

Aubrey de Grey: No — in the end that program was not successful enough to continue with, so we stopped it. There is now more interest in ALT in other labs than there was, though, so I’m hopeful that progress will be made. But also, one reason why I felt that it was OK to stop was that cancer immunotherapy is doing so well now. I think there is a significant chance that we won’t need WILT after all, because we will really truly defeat cancer using the immune system.

Ariel Feinerman: Spiegel Lab has recently published an abstract where they say they have found 3 enzymes capable of breaking glucosepane. Very exiting info! When can we hear more on their research? Revel LLC is a very secretive company.

Aubrey de Grey: They aren’t really being secretive, they are just setting up.

Ariel Feinerman: When can we see the first clinical trial of glucosepane breaker therapy?

Aubrey de Grey: I think two years is a reasonable estimate, but that’s a guess.

Ariel Feinerman: What do you think of the Open Source approach in rejuvenation biotechnology? The computer revolution in the early 2000s has taken place only because Open Source caused an explosion in software engineering!

We have many examples when Big Pharma buys a small company which has patents on technology and then cancels all research. In the Open Source approach you cannot “close” any technology, while everyone can contribute, making protocol better and everyone can use that without any licence fee! Anyway, there are countries where you cannot protect your patents. Maybe it will be better to make technology open from the beginning?

Famous biohacker Josiah Zayner said: “In the gene therapy world most treatments are easy to replicate or pirate because you can reverse engineer the DNA from scientific papers or patents. Same exact treatment, same purity and quality I could give to someone rejected from the clinical trial. The cost? Hundreds or a few thousand dollars at most. Same deal with immunotherapy.”

Aubrey de Grey: I think you’ve pretty much answered your own question with that quote. The technologies that will drive rejuvenation are not so easy to suppress.

Ariel Feinerman: Is the SENS RF going to begin new research programmes in 2019?

Aubrey de Grey: Sure! But we are still deciding which ones. We expect that our conference in Berlin (Undoing Aging, March 28–30) will bring some new opportunities to our attention.

Ariel Feinerman: What are your plans for 2019?

Aubrey de Grey: I’d like to say less travelling, but that doesn’t seem very likely at this point. Really my goal is just to keep on keeping on — to do all I can to maintain the growth of the field and the emerging industry.

Ariel Feinerman: Thank you very much for your answers, hope to see you again!

Aubrey de Grey: My pleasure!

Ariel VA Feinerman is a researcher, author, and photographer, who believes that people should not die from diseases and ageing, and whose main goal is to improve human health and achieve immortality. If you like Ariel’s work, any help would be appreciated via PayPal: arielfeinerman@gmail.com.

The 2020 Undoing Aging Conference Will Take Place May 21 to 23 in Berlin, Germany – Announcement by Undoing Aging

The 2020 Undoing Aging Conference Will Take Place May 21 to 23 in Berlin, Germany – Announcement by Undoing Aging

Undoing Aging


Editor’s Note: The U.S. Transhumanist Party features this announcement by the Undoing Aging Conference, a joint project between the SENS Foundation and the Forever Healthy Foundation,  originally published on their site on April 2, 2019.  The Undoing Aging Conference is focused on the cellular and molecular repair of age-related damage as the basis of therapies to bring aging under full medical control. Undoing Aging 2020 will once again bring together scientists and startups from around the globe, all pioneers in their respective fields, who are leading the charge in maintaining and restoring full health in old age. Such research is supported by the U.S. Transhumanist Party as part of our policy goals.

~ Brent Reitze, Applicant for Director of Publication, United States Transhumanist Party, April 4, 2019


April 2, 2019  Mountain View, California / Berlin, Germany

After the incredible success of the 2019 Undoing Aging Conference, SENS Research Foundation and Forever Healthy Foundation are pleased to announce Undoing Aging 2020, which will take place on May 21 – 23. As UA2019 was sold out with nearly 500 participants from over 30 countries, Undoing Aging 2020 will be moving to a larger venue.

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The Undoing Aging Conference is focused on the cellular and molecular repair of age-related damage as the basis of therapies to bring aging under full medical control.  Among the 40 brilliant speakers at Undoing Aging 2019, there were giants in regenerative medicine such as: Dr. Nir Barzilai, Dr. Jerry Shay, Dr. Evan Snyder, Dr. Judith Campisi, and many more. Undoing Aging 2020 will once again bring together scientists and startups from around the globe, all pioneers in their respective fields, who are leading the charge in maintaining and restoring full health in old age. To accommodate the exciting growth of the emerging rejuvenation biotechnology industry, Undoing Aging 2020 will add a dedicated forum and exhibition space for rejuvenation biotech companies to present themselves to prospective investors and industry partners.

Additionally, the 2020 conference will add a special “Rejuvenation Now” session highlighting the first generation of human rejuvenation therapies that are either currently in clinical trials or are available today.

Undoing Aging 2020 is not only open to the scientific community, but also welcomes startups, investors, the general media, and all interested members of the broader rejuvenation movement. The conference will feature a student poster session showing the work of innovative undergraduate and graduate students in the field of damage repair.

“The accelerating rate of progress in rejuvenation research is now unmistakeable at all levels: publications, transfer into rapidly-funded startup companies, and even into the clinic. One marker of this is the worldwide proliferation of conferences focused on it. But I have no doubt that Undoing Aging will maintain its pre-eminence among them, with its strong focus on the most cutting-edge science, its long history dating back to my first Cambridge conference in 2003, and above all its steadfast support from Forever Healthy,” said Dr. Aubrey de Grey, CSO of SENS Research Foundation.

“We are very excited to work with SENS on Undoing Aging,” stated Michael Greve, founder, and CEO of the Forever Healthy Foundation. “Forever Healthy has two key goals for this conference: To support the remarkable scientific community and the rejuvenation biotechnology startups already working on repair of age-related damage and to create an unique opportunity to experience that bringing aging under complete, genuine medical control is realistic, achievable, and, indeed, beginning to happen.“


About Forever Healthy Foundation
Forever Healthy is a private, non-profit initiative with the mission to enable people to vastly extend their healthy lifespan and be part of the first generation to cure aging.

Thru its ‘Rejuvenation Now‘ and ‘Maximizing Health‘ initiatives, Forever Healthy seeks to continuously identify and evaluate new rejuvenation therapies on risks, benefits, and potential application and to harness the enormous wealth of the world’s cutting-edge medical knowledge to empower informed decisions about health and well-being.

In addition, Forever Healthy supports the development of rejuvenation therapies that undo the damage of aging by funding basic research, bringing together the world’s leading scientists at the Undoing Aging conference and supporting startups that work on actual therapies for human use. For more information, please visit forever-healthy.org

About SENS Research Foundation
SENS Research Foundation is a 501(c) nonprofit that works to research, develop and promote comprehensive regenerative medicine solutions for the diseases of aging. The foundation is focused on a damage-repair paradigm for treating the diseases of aging, which it advances through scientific research, advocacy, and education.

SENS Research Foundation supports research projects at universities and institutes around the world with the goal of curing such age-related diseases as heart disease, cancer, and Alzheimer’s disease. Educating the public and training researchers to support a growing regenerative medicine field are also significant endeavors of the organization that are being accomplished through advocacy campaigns and educational programs. For more information, please visit sens.org

To stay updated on Undoing Aging, you can follow their facebook page.

Aubrey de Grey – Clinical Trials in Five Years – Interview by Laura Sanz Olacia

Aubrey de Grey – Clinical Trials in Five Years – Interview by Laura Sanz Olacia

logo_bgLaura Sanz Olacia
Aubrey de Grey


Editor’s Note: In this interview originally published by our allies at the Life Extension Advocacy Foundation (LEAF), Laura Sanz Olacia discusses with Dr. Aubrey de Grey his anticipation that treatments aimed at reversing biological aging may enter clinical trials within five years. The U.S. Transhumanist Party is pleased to feature these insights from Dr. de Grey. 

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, December 18, 2018

 


In November, Dr. Aubrey de Grey, a graduate of the University of Cambridge, was in Spain to attend the Longevity World Forum in the city of Valencia, and he gave a press conference organized by his friend, MIT engineer José Luis Cordeiro.

Dr. Aubrey de Grey is the scientific director (CSO) and founder of the SENS Research Foundation. In Madrid and Valencia, Dr. de Grey reaffirmed for Tendencias21 one of his most striking statements of 2018: “In the future, there will be many different medicines to reverse aging. In five years, we will have many of them working in early clinical trials.”

The Longevity World Forum is a congress on longevity and genomics in Europe. It is heir to the first congress in Spain, the International Longevity and Cryopreservation Summit, which was held at the CSIC headquarters in Madrid in May 2017, and Dr. de Grey also participated in that event. In Valencia, his presentation was recieved with interest, and Dr. de Grey explained to this select audience that aging will be treated as a medical problem in the near future. Rather than treating its symptoms using the infectious disease model, the root causes of aging will themselves be treated.

It was published recently on longevityworldforum.com that a therapy to reverse aging will be a reality within five years. What will be its mechanism of action, roughly?

There will not be just one medicine; there will be a lot of different medicines, and they will all have different mechanisms of action. For example, some of them will be stem cells, where we put cells back into the body in order to replace cells that the body is not replacing on its own. Sometimes, they will be drugs that kill cells that we don’t want. Sometimes, they will be gene therapy treatments that give cells new capabilities to break down waste products, for example. Sometimes, they will be vaccines or other immune therapies to stimulate the immune system to eliminate certain substances. Many different things. In five years from now, we will probably have most of that working. I do not think that we will really have it perfect by then; probably, we will still be at the early stages of clinical trials in some of these things. Then, we will need to combine them, one by one, to make sure that they do not affect each other negatively. So, there will still be some way to go. But, yes, I think it’s quite likely that in five years from now, we will have everything, or almost everything, in clinical trials.

Then clinical trials for seven years until it’s perfected. Don’t clinical trials usually take a long time?

It depends. For example, in aging, because there is this progressive accumulation of damage, you could have therapies that slow down the rate at which damage accumulates, or you could have therapies that repair the damage that has already happened. The second type of therapy is what we think is going to be most effective and is going to be easiest to do, and you can see results from that very quickly, like in one or two years. Now, of course, you still want to know what happens later on, but the first thing is to determine whether this is working at all, and as soon as it starts to work, then you can start to make it available. Clinical trials are changing in that way. Historically, clinical trials had to be completed before anybody could get these drugs, but now we are getting new policies; there is a thing called adaptive licensing, which is becoming popular in the US and elsewhere, where the therapy becomes approved at an earlier stage, and then it’s monitored after that.

Beyond the humanitarian perspective of avoiding the pain and suffering that comes with old age, if increasing the years of healthy life in people will significantly reduce health care spending by governments, why don’t they promote research in this area?

You’re absolutely right. It’s quite strange that governments are so short-sighted. But, of course, the real problem is psychological: it’s not just governments that are short-sighted. Almost everybody in the world is short-sighted about this. The reason I believe why that’s true is people still can’t quite convince themselves that it’s going to happen. Since the beginning of civilization, we have known that there is this terrible thing called aging, and we have been desperate to do something about it, to get rid of it. And people have been coming along, ever since the beginning of civilization, saying, “Yes, here’s the solution, here’s the fountain of youth!” And they’ve always been wrong. So, when the next person comes along and says they think they know how to do it, of course, there is going to be some skepticism until they have really shown that it’s true. Of course, if you don’t think it’s going to work, then you’re not going to support the effort financially. It’s very short-sighted, but it’s understandable.

Why do you think that the pharmaceutical industry does not devote its research and development efforts to this area, which causes the death of 100,000 people every day?

Today, the pharmaceutical industry is geared toward keeping old people alive when they are sick. It makes its money that way. It’s not just the pharmaceutical industry, it’s the whole of the medical industry. And so, most people say that they are worried that maybe the pharmaceutical industry will be against these therapies when they do come along. I don’t think that’s true at all. I think they will be in favor because people will be in favor, but people are not really in favor yet. People don’t really trust preventive medicine. They think “Okay if I am not yet sick…” They don’t trust medicine in general; they know that this is experimental. So, when they are not yet sick, they think “Well, I’ll wait until I am sick,” but we can change that. Eventually, people will understand that it’s going to be much more effective to treat yourself before you get sick, and then the whole medical industry will just respond to that; they will make the medicines that people want to pay for.

So you don’t think that they will be against these therapies?

No. They will follow.

But now, they are not focusing their research into this field.

That’s right because they don’t need to. The big pharmaceutical companies don’t really do much of their own research in the first place. They just wait to see what happens, and then they buy small companies.

In the car analogy that you use, you say that a car is built to last 10 or 15 years, but with proper maintenance, it can last up to 100 years. Isn’t this expressing the idea that aging is programmed and that the life of a car is also programmed?

No, it’s not. All of you know that, a long time ago, Henry Ford invented a concept called planned obsolescence, which was a way of building a car so that you could predict pretty accurately how long it would last. But, of course, the only reason that the prediction works is because people are lazy, and they don’t mind replacing their cars, so they only do the minimum amount of maintenance that the law tells them to. The reason that some cars last 100 years is not because those cars were built differently, it’s because there are a few people out there who fall in love with their cars and they don’t want them to get old. So, it really is exactly the same. In the human body, we have aging, because there are certain types of damage that are not automatically repaired when they happen. Of course, many types of damage in the human body are repaired automatically when they happen, so we don’t need medicine for that, but some of them are not. So, if we can develop medicines that do fix those things, it’s exactly the same as with a car.

If aging is not programmed, why do different species have different lifespans?

Because they have different qualities of built-in repair machinery. When I talk about all these types of damage, they are the types of damage that accumulate in the body, and they accumulate because the body does not have ways to repair them. There are massive amounts of other types of damage that I don’t call damage, and the reason I don’t call them damage is because they don’t accumulate. The reason that they don’t accumulate is because we already have built-in machinery to repair them when they happen. So, long-lived species have more comprehensive automatic repair machinery built into them.

Do you think that first we can focus on just replacing organs and restoring their function, and eventually we can eliminate the root causes of aging? Once we reach longevity escape velocity, maybe we can focus on just eliminating it?

We will never be able to stop the body from creating this damage. The body is going to do that because it is intrinsic to metabolism, but the better we get at repairing the damage, the fewer problems we have.

What healthy habits do you follow now?

I don’t do healthy habits. I’m lucky, I don’t need to do anything; I can drink whatever I like and nothing happens. I don’t even do much exercise, and also I don’t get nearly enough sleep, which is probably shortening my life, but it is worth it because I am hastening the defeat of aging, so it is a net positive.

Which generation will live to be a thousand years old? Do you think it is born already?

I think it is very probably born already, yes. But, of course, we cannot know until we get the medicines.

Which country do you think is more aware, or the people is more aware that this is a problem that we need to fix?

I would say Russia.

Russia?

Yeah. Surprising, isn’t it? But when I go to Russia and I talk about all of this, it’s so wonderful; I don’t get any of the uninformed questions, and everyone seems to understand it.

They don’t ask you ethical questions?

That’s right, yeah. They understand that this is a medical problem, it needs to be fixed, and it can be fixed.

Kriorus [the first and only cryonics company in Eurasia] is there right?

Yeah, I know Kriorus, I know the people very well.

Alcor [the world leader in cryonics located in Arizona] is the most expensive.

It gives the best service. I mean, it makes sense to have a very expensive, high-quality service and also less expensive and lower quality service. That is normal.

Where are you currently living?

I live in the United States, but I go everywhere when I am invited to speak and so on.

Laura Sanz Olacia, has a degree in Pharmacy from the Complutense University of Madrid (2015). Between 2016 and 2017 she worked for nine months in different pharmacies in London. She also worked in a pharmacy laboratory compounding medicines and cosmetics in Madrid. More recently she worked in IQVIA as Data Management Analyst. She is very interested in research and, in particular, in the area of ​aging. During her stay in London, she participated in the organization of the Antiaging Conference London 2016, and back in Madrid, she collaborated closely with the organizing committee of the International Longevity and Cryopreservation Summit 2017. She wants to devote her career to doing research in this field.

Interview with Dr. Aubrey de Grey by Yuri Deigin

Interview with Dr. Aubrey de Grey by Yuri Deigin

logo_bg

Yuri Deigin
Aubrey de Grey


Editor’s Note: The U.S. Transhumanist Party is pleased to publish this in-depth interview by Yuri Deigin of Dr. Aubrey de Grey, the U.S. Transhumanist Party’s Anti-Aging Advisor. Herein Dr. de Grey offers original, in-depth insights regarding the current state of research and public opinion regarding the pursuit of advances in rejuvenation biotechnology that will hopefully achieve significant life extension, one of the U.S. Transhumanist Party’s Core Ideals, within our lifetimes.  This interview was originally published in the Russian language here. The English-language version was first published by one of the U.S. Transhumanist Party’s Allied Organizations, the Life Extension Advocacy Foundation (LEAF), here

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, July 29, 2018

Note from the Life Extension Advocacy Foundation (LEAF): Today we have an interview with Dr. Aubrey de Grey from the SENS Research Foundation. This interview conducted by Yuri Deigin, CEO at Youthereum Genetics, was originally published in Russian language and he has kindly translated it into English so our audience can enjoy it, too.


Yuri: Aubrey, thank you very much for agreeing to this interview. Why don’t we dive right in? I am sure everybody asks you this: how and when did you become interested in aging, and when did you decide to make it your life’s mission to defeat it?

Aubrey de Grey: I became interested in aging and decided to work on it in my late 20s, so, in the early 1990s. The reason I became interested was because that was when I discovered that other biologists were almost all not interested in it. They did not think that aging was a particularly important or interesting question. I had always assumed, throughout my whole life, that aging was obviously the world’s most important problem. I thought that people who understood biology would be working on it really hard. Then, I discovered that wasn’t true and that hardly any biologists were working on it. The ones that were weren’t doing it very well, not very productively as far as I could see. I thought I’d better have a go myself, so I switched fields from my previous research area, which was artificial intelligence.

Yuri: By the way, do you think there are disproportionately many people from computer science in aging research these days?

Aubrey de Grey: There are a lot, and there are lots of people who are supporting it. Most of our supporters are, in one way or another, people from computer science or from mathematics, engineering, or physics. I think the reason why that has happened is actually very similar to the reason why I was able to make an important contribution to this field.

I think that people with that kind of background, that kind of training, find it much easier to understand how we should be thinking about aging: as an engineering problem. First of all, we must recognize that it is a problem, and then we must recognize that it is a problem that we could solve with technology. This is something that most people find very alien, very difficult to understand, but engineers seem to get it more easily.

Yuri: So do you think that people who don’t have such a background, this way of thinking, have a chance of understanding the importance of this problem, or are they better off letting people with an engineering mindset figure it out?

Aubrey de Grey: Well, of course, there is always an overlap. The reason I spend so much time doing interviews and running around the world giving talks is precisely in order to help people, for whom this is not obvious, to think about these things. For any new idea or any new way of thinking, there are always people who understand it first and who then communicate that knowledge to other people.

Yuri: Right. And you have been running around giving talks for a very long time, as I understand. It’s been, what, twenty years?

Aubrey de Grey: Well, at least 15 years that I’ve been doing a lot of it.

Yuri: So between the time in your twenties, when you realized that aging is not something that’s being adequately covered by biologists, and the time when you decided to have a go at it yourself, how many years have passed? And can you give a bit more background on when you founded SENS and what SENS is?

Aubrey de Grey: Sure! The year in which I switched fields properly is probably 1995. For the next five years, I was basically just learning. I was going to all the conferences, getting to know the right people, leaders in the field. Learning a lot of what was known and doing a huge amount of reading, of course. The big breakthrough came in the summer of 2000 when I realized that comprehensive damage repair was a much more promising option then what people had been doing before. Since then, it has been a matter of persuading people of that.

There were a few years when I was just ignored and people thought I was crazy and didn’t think I made any sense. Then, gradually, people realized that what I was saying was not necessarily crazy. Some people found it threatening, so in the mid-2000s, I had a fair amount of battles to fight within academia. That’s normal; that’s what happens with any radical new idea that is actually right, so that happened for a while. This decade, it’s been rather easier. We founded the SENS Foundation; we’ve started getting enough donations into the SENS Foundation to be able to do our own research, both within our own facilities as well as funding research at universities and institutes. Gradually, this research had moved far along enough that we could publish initial results. Over the past two or three years, we’ve been able to spin off a bunch of companies that we have transferred technology to so that they can actually attract money from investors.

There are, of course, an awful lot of people out there who believe in what we are doing, but they fundamentally don’t like charities; they don’t like to give money away. They have been waiting for the point when these projects move far enough ahead that they are investable, and that’s resulting in much more money flowing into these areas.

Yuri: This is a good point you bring up – that a lot of wealthy people for some reason aren’t prepared to spend money on fundamental research on aging but somehow desire a financial return on their investments in this field. Do you know why that is? Why can’t they realize that in their position, it is much more rational to try to convert their wealth into something much more valuable that they cannot yet ever get back, which is years of healthy life. Why do they try to also make money on this research?

Aubrey de Grey: Well, it’s not really a rational decision, and it’s different for every individual, whether it’s for that reason or any other. Let me first say that it actually seems less of a problem in Russia. Our single biggest donor at the moment is Vitalik Buterin, the guy who created Ethereum, who is a Canadian of Russian heritage. Another major donor of ours is a guy named Michael Antonov, one of the co-founders of Oculus. I think maybe Russians have less of a problem with this. However, in general, the kind of people who have a lot of money and who are also visionary enough and understand technology enough, they tend to be the kind of people who made their money by doing certain things; they got it through the capitalist system. So, those kinds of people are inherently biased in favor of that system and against philanthropy. Then, of course, there are many other reasons. There are some people who won’t give us money because they don’t think it’s a good idea to defeat aging. There are plenty of people who want to give us money, but their wives think it’s crazy. I am not kidding! There are at least a couple of our major verbal supporters who I know for a fact that that’s why they are not giving us significant amounts of money. Another reason, I think, is that some people just have overly big egos, so they think they can do better than us even when they can’t.

Yuri: Let me probe you a little bit more on this. You brought up wealthy Russians and people who think they can have a go at aging themselves. Would Sergey Brin qualify as one of those people who decided they know better and founded their own company, Calico, for precisely this reason?

Aubrey de Grey: Yeah, I had a funny feeling you might ask me about that. I have a very low opinion of Calico. The fundamental reason for this is because of Larry and Sergey. In fairness to Sergey, my understanding is that Calico is mainly a Larry project, or at least more so than a Sergey project. Of course, they are both on the Board of Directors, and they both share the responsibility. At the end of the day, Calico is a catastrophe, and it’s their fault. They just created it wrongly.

They’ve known me for fifteen years; they could easily have told me, “Listen. We don’t like charity. We want to create a company, and we want you to run it,” and I would’ve said “No problem!” and they knew that. Instead, they decided to be more traditional about this. I don’t know why. Maybe they don’t like people who have beards.

The fact is that they made an absolute catastrophe of it. They started out reasonably sensibly by hiring Art Levinson, the world’s best biotech CEO, but what they didn’t do was tell him what to do next. They gave him a job to cure aging, and he doesn’t have the slightest idea how to cure aging, and he knows that he doesn’t have the slightest idea. So, he hired someone who he thought would have an idea how to do it and made him Chief Science Officer. Unfortunately, he didn’t know how to make that decision either, so he hired completely the wrong person. He hired a completely inveterate basic scientist, David Botstein, who is a fantastic scientist but who doesn’t understand technology. In fact, he went on record saying that he doesn’t have a translational bone in his body. You don’t get that sort of person to run an outfit that’s supposed to be solving a technological problem. Sure enough, they are doing fantastic research that will understand aging better and better as time goes on over the next century, but they will never, ever, if they follow their current strategy, actually make any kind of difference in how long people can stay healthy and, therefore, how long they can stay alive.

Yuri: Why do so few people have a sense of urgency that we need to do everything possible to combat aging within our lifetimes and not centuries to follow?

Aubrey de Grey: There are two answers to that. The David Botstein answer, the Calico answer, is that they just don’t understand the idea of knowing enough. People who work on basic science understand how to find things out, but that’s all they understand. For them, the best questions to work on are the questions whose answers will simply create new questions. Their purpose in life is to create new questions rather than to use the answers for a humanitarian benefit. They don’t object to humanitarian benefit, but they regard it as not their problem. You can’t change that. Botstein is a fantastic scientist, but he’s in the wrong job.

The other part of your question, why people, in general, do not regard aging with a sense of urgency, has a different answer. People weigh up the desirability and the feasibility. Remember that everyone has been brought up to believe that aging is inevitable, I mean completely inevitable in the sense that stopping it would be like creating perpetual motion. If the probability of doing something about this thing is zero, then the desirability doesn’t matter anymore. So, under that assumption, we really ought to put it out of our minds and get on with our miserably short lives. That’s all we can do.

Yuri: So it’s a case of learned helplessness?

Aubrey de Grey: Yes, exactly, it is learned helplessness, and it’s a perfectly reasonable, rational thing to be thinking until a plan comes along that can actually solve the problem: a plan that demonstrates that we actually might be within striking distance of genuinely solving the problem. That only happened quite recently. Of course, I have a huge mountain to climb to persuade people that we have crossed the boundary from this being just a recreational, exploratory field to it being a technological, translational field.

Yuri: Have you had success in the past fifteen years that you’ve been climbing this mountain; have you seen that the public’s perception has greatly improved?

Aubrey de Grey: Absolutely. Things have got hugely easier. I mean, there is a huge amount of the mountain still to climb, but we have climbed a hell of a lot of it. Just the nature of a conversation, the kinds of people who want to hear about this. The way in which credentialed scientists with reputations that they need to protect are willing to embrace this. We could not conceivably have created the scientific advisory board that we have now fifteen or even ten years ago. There are thirty people there who are all world-leading luminaries in their fields, and they are all signed up very explicitly to the ideas that comprehensive damage repair is a thing and that it actually has a good chance of genuinely defeating aging. So, I’ve won the scientific argument.

People are even reinventing the whole idea of comprehensive damage repair and pretending it’s a new idea. Five years ago, there was a paper called “The Hallmarks of Aging” published by five very senior professors in Europe. That paper is saying pretty much exactly what I said eleven years before it. The key difference is that unlike my work, this work is being noticed. In fact, it’s been more than noticed. It’s become the definition of what’s useful work to do. This one paper that was only published 5 years ago has been cited more than 2,000 times already. There’s no question that it’s going to be, by far, the most highly cited paper in the whole of the biology of aging this decade, and it has the same ideas that I put forward the previous decade. So that’s fantastic. I’d like to have more credit, but I really don’t care about that; what I care about is that the idea is now in the mainstream.

Yuri: You mentioned your plan for comprehensive damage repair; could you elaborate a little bit more on what the plan actually is?

Aubrey de Grey: Sure. The idea is to emulate what a mechanic would do to maintain a car. We know that this works; there are cars over a hundred years old that are still running and are doing so just as well as when they were built. We know that they are not doing that because they were designed to last that long; they were probably designed to last only ten years. They’ve vastly exceeded their warranty period, and they’ve done so because of comprehensive damage repair.

The only reason that we can’t do this to the human body already is that the human body has more complexity and more types of damage. However, it’s a manageable amount of complexity. In particular, the big thing that led me through to this route was when I realized back in the year 2000 that we could classify all of the types of damage that the body accumulates into seven major categories, for each of which there’s a generic approach to fixing it.

For example, one of the categories is cell loss, which is when cells are dying and not being automatically replaced by the division of other cells. The repair, of course, is stem cell therapy. We simply put cells into the body that have been pre-programmed into a state where they know what to do to divide and transform themselves into replacements for the cells that the body is not replacing on its own. That’s just one of the seven types of damage that I enumerated, and, of course, that direction is very well advanced. We have hardly ever done any work in stem cells because we didn’t need to; other people are doing all of the work that’s necessary.

The other six categories are more neglected; they are in an earlier stage. That’s why we created the SENS Foundation to push them forward. We’ve been very successful. A number of those things have reached a point where we could actually create a startup company and transfer technology into it, so it would attract investment from the kinds of people I was mentioning earlier who don’t like to give money away.

Yuri: So you’ve created several startups, could you elaborate on the ones that have the most potential?

Aubrey de Grey: They’re all doing pretty well. Let me just focus on one as an illustration: Ichor Therapeutics. Ichor is all about macular degeneration, which is, of course, the number one cause of blindness in the elderly. The category in SENS that it comes under is the accumulation of molecular waste products inside cells. They accumulate in different cells in many different ways. It’s a side effect of their normal operation. Different cells accumulate different types of waste products. One of them is a byproduct of vitamin A that is created in the eye as a side effect of the chemistry of vision, and it poisons cells at the back of the eye called retinal pigmented epithelial cells.

What we’ve done is identify enzymes in bacteria that are able to break down this toxic waste product. If they can break it down, the waste product no longer accumulates. We have identified the genes for these enzymes, and we’ve been able to incorporate them into human cells in such a way that they still work. Ichor is pursuing that, and it will probably soon start clinical trials to pursue this as a cure for macular degeneration later this year. This is dry macular degeneration, the major form in the elderly.

Yuri: Could you tell us about some other startups that you’ve spun out from SENS?

Aubrey de Grey: Sure. Ichor was part of LysoSENS. Another one that we’ve spun off is called AmyloSENS. We’ve got a problem of waste products that accumulate not inside the cells but in the spaces between the cells. In theory, those waste products are easier to get rid of, because they’re inherently easier to break down. The way we do it is by actually getting cells to swallow this stuff, internalize it, and then break it down. There are various ways to trick the immune system into doing that. In the case of Alzheimer’s, this was done some years ago, and it’s already working in clinical trials.

Our focus has been on other types of waste products that are similar to the plaques in Alzheimer’s disease, but they consist of different proteins, and they occur in different tissues. We’ve been able to fund a group in Texas that was able to create some antibodies that could break down the extracellular garbage which is actually the number one killer for really old people, people over the age of 110. That’s now been turned into a company.

Another example is a company that’s being run by the person who used to be our Chief Operating Officer. It’s a company focused on organ preservation. It’s well-known that there’s a huge shortage of organs for transplants. Many thousands of people die every year on waiting lists, just waiting for an organ that is sufficiently immunocompatible for them and that happens to be donated by somebody who dies really nearby. That is a requirement for that organ to be given to the recipient fast enough before it breaks down. We want to solve that transport problem and create whole banks of organs with a variety of immunological profiles. In order to do that, we need to be able to freeze them, but in order to freeze them, we need to develop ways that will not cause damage to the organ in the process of freezing. The company we spun out has got a wonderful new technology that is really good at that.

Yuri: Is that Arigos? The company that uses helium persufflation for cryopreservation?

Aubrey de Grey: That’s the one. You are very well-informed!

Yuri: Can you comment on Human Regeneration Biotechnologies?

Aubrey de Grey: That was our first spin-off, actually. It’s now got a shorter name. It’s called Human Bio, and it’s run and funded by a guy named Jason Hope, who was, for some time, one of our most major donors. He’s now focusing his funding on the company. It was initially created to do something very similar to what we’re doing with Ichor in macular degeneration. In that case, it was for atherosclerosis. The target was not this byproduct of vitamin A; instead, it was oxidized cholesterol, and they have kind of run into the sand a little bit on that. We’re trying to reactivate it right now, but they’ve got other interests as well. They’re working on senolytics, drugs that will kill senescent cells. They are potentially going to be quite a big player in a number of different areas at SENS. At the moment, they are a bit stealthy; they don’t need money, because they are funded by this wealthy guy. They are not going around telling everyone all that much about what they are doing, the way that most of these companies are.

Yuri: What about enzymes that are meant to break glucosepane crosslinks? Is there a startup for that?

Aubrey de Grey: We have funded research on glucosepane at Yale University. We’ve funded that for about 4-5 years now. They had a fantastic publication 2 years ago, where they made a huge breakthrough in this area. Essentially, they first had to be able to make glucosepane in large quantities without a high expense. That was published in Science; that’s our highest-profile publication in any area. It was important because it allowed them to proceed with obvious things, such as identifying enzymes that could break it. That was very successful: they have identified half a dozen enzymes that seem to be promising. For a couple of those enzymes, there’s a pretty good understanding of how they work. Now is the right time to create a company out of that, and that’s exactly what’s happening. That company is a month or two from being incorporated, and its funding is established.

Yuri: Great, so we’ll be on the lookout for an announcement for that company to be spun off.

Aubrey de Grey: It’s going to be called Revel.

Yuri: Ah, let’s hope we can one day revel in its accomplishments.

Aubrey de Grey: That’s right!

Yuri: We might have gotten a bit too deep into science for a casual reader. Maybe we can step back and you could elaborate on what you think actually causes aging? I know there are different schools of thought on that in the scientific community so maybe you can share your perspective?

Aubrey de Grey: I get rather sick of this question, actually. You know, there’s nothing that “causes” aging. What causes the aging of a car? You wouldn’t ask that question: you know that that’s a stupid question. All I really want to tell you is that the aging of a living organism is no different fundamentally than the aging of an inanimate machine like a car or an airplane. Therefore, questions like “What causes aging?” are no more sensible for a living organism than they are for a car.

Yuri: If the underlying causes of aging are the same for all organisms, why do you think there’s such a big difference in lifespan between different species: some live for just a few months, while others for centuries?

Aubrey de Grey: The analogy with inanimate machines like cars works perfectly well there too. Some cars are designed to last 50 years, like Land Rovers, for example, but most cars are only designed to last 10 years. It’s just the same for living organisms. Some living organisms have evolved to age more slowly. A perfectly good question is what causes evolution to create this disparity? Some species in a particular ecological niche, say, at the top of the food chain have an evolutionary imperative to age slowly, whereas species that get eaten a lot don’t need to have good anti-aging defenses built into them. That’s really the basis for why there is this variation in the rate of aging across the living world.

Yuri: The more interesting question is when will humanity actually conquer aging?

Aubrey de Grey: It all depends on how rapidly research goes, and that depends on money. Which is why when people ask me, “What can I do today to maximize my chances of living healthy and for a long time?” I tell them to write me a large check. It’s the only thing one can do right now. The situation right now is that everything we have today – no matter how many books are written about this or that diet or whatever – is that basically, we have nothing over and above just doing what your mother told you: in other words, not smoking, not getting seriously overweight, and having a balanced diet. If you adhere to the obvious stuff, you are doing pretty much everything that we can do today. The additional amount that you can get from just any kind of supplement regime, diet, or whatever is tiny. The thing to do is hasten the arrival of therapy for the betterment of what we have today. That’s where the check comes in.

Yuri: Some people probably couldn’t afford to write a sizable check; maybe they can do something else?

Aubrey de Grey: What I always say in relation to that is that the poorer you are, the more people you know who are richer than you. Therefore, the less you can do in terms of writing your own check, the more you can do in terms of persuading other people to write checks.

Yuri: So it’s activism, being vocal about aging research?

Aubrey de Grey: Absolutely. It’s activism and advocacy: it’s all about spreading the word and raising the level of people’s understanding of the fact that aging is the world’s biggest problem.

Yuri: Do you see any increase in funding for longevity research over the past 10 years?

Aubrey de Grey: Things have certainly improved. I mean, there’s more money coming into the foundation, a little bit more money, but there’s a lot more money coming into the private sector, into the companies I mentioned and other companies that have emerged in parallel with us. The overall funding for rejuvenation biotechnology has increased a lot in the past few years, and we need it to increase a lot more. The private sector can’t do everything, not yet, anyway. There will come a time when SENS Research Foundation will be able to declare victory and say, “Listen, everything that needs to be done is being done well enough in the private sector that we no longer need to exist.” For the moment, that’s not true. For the moment, there are still quite a few areas in SENS that are at the pre-investable stage where only philanthropy will allow them to progress to the point where they are investable.

Yuri: It’s great to hear that there is money coming into SENS because from what I understand, there was a time when you had to use your own money to fund the foundation, is that correct?

Aubrey de Grey: That’s right. I inherited 16.5 million dollars of which I donated 13 million. That was back in 2012 before we had any projects that we could spin out into companies. That inheritance was very timely, but the point is that I would still do it even now. If my mother died today, I’d probably do the same thing, because the foundation is still the engine room of the industry. For the foundation, it’s kind of double aid. The more progress we make, the more credible the whole idea becomes, which, of course, improves our ability to bring in money. We are also creating new opportunities where you can invest rather than donate, so it’s kind of a disincentive to donate. There’s a balance there. Of course, every donor is different; some donors are more philanthropically inclined than others.

Yuri: From what I understand, you’ve had some high-profile donors like Peter Thiel who’s been supporting the foundation for a number of years. Is he still a supporter?

Aubrey de Grey: Peter started supporting us in 2006, 12 years ago. He’s actually pretty much phased out now. I understand that. Ultimately, he’s much more comfortable with investing than donating. He wanted to be sure that we’re actually creating something, and sure enough, we are. We speak all the time to his investment advisors, who focus on investment opportunities in the biotech sector, especially in the anti-aging sector. I’m sure that he will continue to contribute financially to this field, though the contributions are quite likely to be focused more on the companies rather than the foundation.

One way in which Peter is donating indirectly right now is that he funded Vitalik Buterin four years ago as a Thiel Fellow under the 20 Under 20 program. That was how and where Vitalik created Ethereum, which of course made Vitalik very wealthy, and Vitalik donated 2.5 million dollars to us a few months ago. He is very much philanthropically inclined. So, Peter is still donating to us by proxy.

Yuri: What about his PayPal co-founder, Elon Musk? Has Peter ever connected you two or maybe you spoke to Elon yourself?

Aubrey de Grey: I have indeed met Elon many years ago, probably 10 years ago. I haven’t met him recently. In general, I think it’s quite unlikely that Elon will get heavily involved in this just because he’s got other things to focus on. It’s a bit like Bill Gates, though in the opposite direction. Bill Gates has pretty much explicitly said that his priority is to help the disadvantaged. He’s much more interested in mosquito nets in sub-Saharan Africa and less interested in people who already have advantages. Elon is kind of at the other end of the spectrum. He is more of a “toys for boys” kind of guy. He’s more interested in space travel and solar energy and so on. The thing is I don’t want to take money away from either one of those two people. I think that both of them are doing fantastic work that really matters for humanity. There are plenty of other people, such as Peter Thiel, who are in the middle, who do understand the enormous value of defeating aging, and who have the vision to understand who is likely to be able to do it, so I don’t want to distract either Elon or Bill from what they’re already doing.

Yuri: Do you think Elon might be moving in a somewhat different direction of mind uploading for circumventing aging?

Aubrey de Grey: Yes and no. I kind of pay attention to what he is doing with Neuralink and what people like Bryan Johnson are doing with Kernel. I am closely connected with those groups. I know a lot of people in that space. At the end of the day, I think they know as well as I do that it’s very, very speculative. Ways in which we might transfer our consciousness, our personality to different hardware, while still satisfying ourselves that we are genuinely the same person after the transfer rather than just creating a new person – those are pretty speculative ideas. There is a long way to go to make them even slightly comparable to something that competes with medical research.

Yuri: So you think that mind uploading, even if theoretically possible, is still far off in the future as something feasible?

Aubrey de Grey: It’s always dangerous these days to say that such and such technology is definitely not going to be developed until some particular number of years in the future. At some point, people said that the game of Go would never fall to a computer, but then AlphaGo came along. However, it is a certainty that the distance that we have to go is much larger in the case of mind uploading than in the case of the boring “wet approach” of medical research.

Yuri: Speaking of AlphaGo and AI, some researchers in the aging space are working AI as a kind of proxy to help us solve biology. What do you think about that approach?

Aubrey de Grey: There is definitely an intersection there. I actually know a lot of people who are at the cutting edge of AI research. I actually know Demis Hassabis, the guy who runs DeepMind, from when he was an undergraduate at Cambridge several years after me. We’ve kept in touch and try to connect every so often. I think it’s reasonable to view these things as very linked. I certainly agree with you that there are some AI researchers who are working on AI precisely because they don’t trust people like me to get the job done by the “wet approach”. That’s fine; they may be right, and if they are right, I’ll be just as happy for them to save my life rather than me saving their lives.

Yuri: Do you think we’re close to having AI help us with biology, or do you think it’s still years away?

Aubrey de Grey: There are some medical AI startups that are looking at ways to use machine learning against aging. One of the most prominent is InSilico Medicine led by Alex Zhavoronkov, which is largely focused on identifying drugs that can work in particular ways. It’s a very important area. I’m sure that we will use AI a lot in medical research in general. Whether we will go as far as supplanting medical research with the mind uploading approach, that’s a different question altogether.

Yuri: One of your most famous quotes is that you think that a person who will live for over 1,000 years has already been born. Do you still think so and what are the chances for, say, a 50-year-old person today to reach what you call Longevity Escape Velocity?

Aubrey de Grey: I certainly think what I used to think, and it is indeed as a result of the concept of the longevity escape velocity. I do not believe that even within the next hundred years, we’re likely to develop therapies that can completely 100% succeed in repairing all the damage that body does to itself in the course of its normal operation. I do believe that we have a very good chance within the next 20-25 years of fixing most of that damage, and most are good enough because it buys time to fix a bit more and then a bit more. The reason it buys time because the body is set up to tolerate having a certain amount of damage without significantly declining function. I think we’ve got a very good chance of getting to that point while we are staying one step ahead of the problem by improving the comprehensiveness of the therapies faster than time is passing.

Yuri: So that is essentially the definition of Longevity Escape Velocity, right?

Aubrey de Grey: Yes, to be precise, Longevity Escape Velocity is the minimum rate at which we will need to improve the comprehensiveness of these therapies subsequent to the point where we get the first ones working so they get us a couple of decades of extra life. The good news is that longevity escape velocity goes down with time, because the more we can repair, the longer it takes for the stuff we can’t repair to become problematic.

Yuri: If you had unlimited funding, how long do you think it would take for us to reach Longevity Escape Velocity or the technology necessary for it?

Aubrey de Grey: It’s actually pretty difficult to answer that question because the amount of funding is kind of self-fulfilling. Every increment of progress that we achieve makes the whole idea more credible, makes more people more interested, and makes it easier to bring in the money to make the next step. I think that, at the moment, unlimited funding could probably let us increase our rate of progress by a factor of three, but that does not mean that we will change the time to get to Longevity Escape Velocity by a factor of three, because when we get even a little bit closer to it, it will be easier to get money, and that factor of three will come down. I think that right now, if we got like a billion dollars in the bank, then, in the next year, we would probably do the same amount of work and make the same amount of progress that we would otherwise make in the next three years. In the year after that, only two years of progress, and in the year after that, only a year and a half, and so on. What that adds up to is that if I got a billion dollars today, we would probably bring forward the defeat of aging by about 10 years. And it’s a lot of lives, maybe 400 million lives.

Yuri: Yes, given that 100,000 people die per day from aging-related causes, it’s a lot of lives.

Aubrey de Grey: Yup.

Yuri: So, you said, “if I had a billion in the bank”. The Chan/Zuckerberg Initiative – they said they are prepared to spend 3 billion dollars to eradicate all diseases by 2099. Maybe they can set aside 1 billion for your work. Did you ever communicate with them?

Aubrey de Grey: All I can say is that my email address is not very difficult to find online. No, we have not been in talks, and they have not made it easy for us to get in touch with them.

Yuri: That’s disappointing, especially given your close geographic proximity and the fact that you probably have an overlapping social and professional network.

Aubrey de Grey: Yes, it is very disappointing. Of course, you can argue that it’s not quite as disappointing as the situation with Calico. Because in the case of Calico we are talking about people with equally deep pockets who have known me for 15 years and who have already decided that aging itself is a thing to target. Zuckerberg, first of all, he never met me, God knows how much he knows about what we even do. Certainly, none of the pronouncements from the Chan/Zuckerberg Initiative indicate that they even understand that aging is a medical problem. They may have a long way to get to the point of even considering this.

Yuri: Yes, they do use some odd phrasing, speaking about “eradicating all diseases”, considering that all age-related diseases have one root cause – the aging process.

Aubrey de Grey: This is part of the problem. People simply should not be using the word “disease” for age-related diseases. The fact is that if a medical condition is age-related, then it’s part of aging, as it mainly affects people who have been born a long time ago. That means that it shouldn’t be described using the terminology that makes people think that it’s a bit like infection. People will often tell each other that I say that aging is a disease or a collection of diseases. But that’s completely wrong: I say the exact opposite. I say that not only should the word “disease” not be broadened to include aging, it should be narrowed to exclude the so-called diseases of old age.

Yuri: So that would be cancer, Alzheimer’s and all kinds of heart conditions…

Aubrey de Grey: Yes, and atherosclerosis, everything that’s bad for people who have been born a long time ago but that very rarely, if ever, affects people in young adulthood.

Yuri: So would you call Alzheimer’s a pathology then? If it’s not a disease?

Aubrey de Grey: I would call it part of aging. The problem is the idea of carving up little bits of aging, pretending that they are separate from each other. They’re not; they’re all parts of – consequences of – a lifelong accumulation of damage.

Yuri: Interesting. There’s been quite a large ongoing effort among the aging research advocacy community to persuade WHO to include aging as a disease in its International Classification of Diseases.

Aubrey de Grey: Yes, it seems to be going quite well, and I am very pleased to see that this effort is being led by some Russians: Daria Khaltourina, who is very much Russian, and by Ilia Stambler, who is from Israel but of Russian extraction. Again, the Russians seem to “get it” much easier than most people and it’s very heartening to me.

Yuri: Do you support this inclusion of aging into ICD as a separate disease?

Aubrey de Grey: The ICD is a little bit different. The “D” in the ICD stands for disease, but the purpose of the ICD is to determine which things medicine should be attacking. It really should be the IC of “medical conditions”. We should be distinguishing medical conditions that are extrinsic, such as infections, from the ones that are intrinsic consequences of being alive, that are age-related. I believe that it would be better if we did that by using different words, but medical conditions of old age are medical conditions, and they ought to be listed in the ICD.

Yuri: I see. Thanks for clarifying! Can I ask you about your new role with Michael West at AgeX and BioTime?

Aubrey de Grey: Michael West and I have been friends for 20 years, and, of course, we have very closely aligned goals in life. We’ve never been able to work together in a formal capacity until now, but we’ve been very much mutual admirers. I’ve always looked up to Mike as someone who, way before anyone else, did something that I thought was impossible with the creation of an actual gerontology research company, as was the case with Geron 20 years ago. He’s done it three times by now: Geron, then Advanced Cell Technology, and now with BioTime.

AgeX is a new subsidiary of BioTime that is about to be floated independently on the stock market. The goal, of course, is very much our goal: damage repair. The area that AgeX is focusing on is stem cells. There are two main themes within AgeX. One of them is stem cell therapy in the normal sense: in other words, injecting stem cells. The particular differentiator that AgeX and BioTime have is the ability to create particularly pure populations of a particular type of stem cells, ones that will only do what you want them to do – they are lineage committed in a particular way. That’s something that other organizations don’t have the ability to do nearly so well, and it’s very important; you want to be able to give the people the type of stem cells they need and not give them the other ones in the wrong place, which might do damage. That’s one side.

The other side of AgeX, which is at a much earlier stage of development, so you shouldn’t be looking out for any products on the basis of this yet, is induced stemness. In other words, it’s giving an organism not stem cells per se but rather reagents that would cause cells already in the body to revert a little bit, become more stem-like and be more able to regenerate the tissues. We already have one compound that has this effect, but we have lots and lots more work to do that will allow this to be done safely and effectively.

Yuri: Is this based on Michael West’s work in planarians, axolotls and other animals that demonstrate the ability to regenerate lost limbs even in adulthood?

Aubrey de Grey: No, not really. Certainly, we pay attention to the regenerative capacity of lower organisms, but the main focus of AgeX’s work is on what happens in early development in mammals, particularly the phase change that happens during early development, which we call the embryonic-fetal transition. It’s a little bit imprecise; we are still characterizing it, and there’s still work to do and stuff to be understood. Basically, what happens is that over a relatively short period of time during development, there is a change in the level of expression in a number of genes; some of them go up, and some go down. The particular change that happens across the entire embryo seems to coincide with – and we think it’s causally related with – the loss of regenerative capacity. In other words, before this transition, a particular type of injury to the embryo is entirely reversed by regeneration, whereas after this transaction, the same type of injury is not reversed, it’s rather patched up with scarring. That’s what happens in the adult as well. We believe that this is very indicative of something that’s going on across the whole body and that has a close relationship with the decline in regenerative capacity and repair capacity against various problems within aging.

Yuri: Is that the COX7A1 gene that was described in a paper in conjunction with Alex Zhavoronkov?

Aubrey de Grey: Yes, COX7A1 is one of the genes that change expression during the embryonic-fetal transition. We do not yet know, or at least we’re not sure, whether it plays a causal role or whether it’s just a marker. We are definitely looking quite a lot at other genes that also change, but COX7A1 is the one we focused on first and most at this point, basically just because it has the sharpest transition in the cell types that we studied so far.

Yuri: Would gene therapy be the vehicle to deliver to the body a way to modulate that gene?

Aubrey de Grey: It might be. Exactly what you do depends on which cell types you decide matter the most in expressing or not expressing a gene and in terms of what gene you want to express. Yes, we might do it with gene therapy. Of course, there are different types of gene therapy. For example, if you want to knock a gene down, you can do RNA interference, which is something that doesn’t involve integrating a new gene into the cell’s DNA. If you want to knock a gene up, you can sometimes also do it by RNA interference, because you can sometimes find the genes that antagonize the gene you want to knock up. If you knock down the gene that antagonizes the gene you want to knock up, then it happens indirectly. There are lots of tricks that are specific to the details of the genetic network, but in general, we would want to manipulate the level of expression and effectiveness of certain genes that change during the embryonic-fetal transition.

Yuri: Can I ask you about a different potential gene therapy, for example, partial reprogramming using Yamanaka factors? Do you think it has any potential as a systemic anti-aging therapy?

Aubrey de Grey: This is the idea that’s actually very similar to what I just described when I talked about the idea of restoration of stemness that we are pursuing at AgeX. Mostly, we don’t know which way is going to work better. We believe that we have a priority in terms of intellectual property, which, of course, is important for investors, but that’s not my problem; I’m focusing on the science.

Obviously, we don’t know which way is going to work best. There are lots of possibilities. The guys who pioneered the idea of partial reprogramming in vivo – there’s a group in Spain led by Manuel Serrano, who is someone I know very well; he’s spoken at one or two of our conferences in Cambridge. He’s a great guy doing a number of other really useful things; he’s got a brilliant new innovation in terms of killing senescent cells as well, which is a completely different area of SENS, of course. More recently, someone in San Diego named Juan Carlos Izpisua Belmonte developed a similar technique that he was able to make work, and his technique involved the intermittent inducible expression of the Yamanaka factors. Essentially, what will determine which of these approaches is the best is not just how well it works but how much harm it does, because there is always a possibility with these things that you will cause cells to become more regenerative that you wished were less regenerative, such as cancer cells, and we need to find a way to control that. It’s possible that AgeX will be able to do this better by using different genes.

Yuri: Okay, great. The reason I knew about Arigos earlier is that I am a big proponent of cryonics. I wanted to ask about your views on cryonics and whether you would personally consider it for yourself?

Aubrey de Grey: Cryonics in general – my position is well known. I’ve been a member of Alcor and a member of its scientific advisory board for 16 years now. I am definitely a very strong supporter. I think that it’s an absolute tragedy that cryonics is still such a backwater publicly and that a large majority of people still believe that it has no chance of ever working. Complete nonsense! If people understood it better, there would be more research done to develop better cryopreservation technologies, and more people would have a chance at life.

The question is what can we do to make cryonics work really well? I certainly don’t have a strong philosophical position with regard to what kinds of revival constitute actual revival and what kinds constitute creating a totally new person from information that you got from the old person. I am not a philosopher, so don’t ask me about that. My personal inclination is that if I have to be cryopreserved at all, and I hope not to be just like any cryonicist, then I prefer to be woken up by being warmed up rather than by being rebuilt from some kind of information restored from slicing and scanning my original brain. Therefore, I am really interested in improving the cryopreservation process: in other words, reducing the amount of damage that is inflicted by the process of cryopreservation and therefore would need to be repaired for successful reanimation; of course, this is along with the damage that the body already had that led to it getting declared legally dead in the first place. Arigos, with its helium persufflation approach, is, in my mind, a massive breakthrough, a breakthrough even bigger than vitrification, which was made 20 or so years ago by Greg Fahy and his peers at 21st Century Medicine when they identified a rather elaborate cocktail of cryoprotectants called M22 that allows biological material of any size to be cryopreserved without any crystallization at all. It eliminated over 90% of the damage that cryopreservation would hitherto have done to biological tissues. After that, it had become the standard of care at Alcor, the Cryonics Institute, KrioRus, and elsewhere.

We need more because the fact is that we still got a lot of cracking that happens – large-scale fracturing – and we’ve also got the toxicity of cryoprotectants, which is mild but non-trivial. Persufflation appears to solve both of these problems pretty much 100% by pumping helium through the vasculature, thereby stopping cracks from propagating, and cooling so much faster that you can vastly lower the concentration of cryoprotectants and still get no crystallization.

Yuri: Did you work with Greg Fahy or Mike Darwin at all on this technology?

Aubrey de Grey: I don’t work with any of these people, but I certainly talk to them. I am not sure what Mike Darwin has done, but Greg, as far as I know, had no work with persufflation itself. Obviously, he pioneered vitrification, but persufflation is something that was first explored in the Soviet Union, I don’t know exactly where, decades ago. Rather like parabiosis, it’s an area that was explored in the Soviet Union and then fell into neglect, and then everyone forgot about it for a long time, and then people in California found out about it and started to do something. The big innovation that Arigos has introduced was using helium, which has a number of advantages for cryonics purposes, but we are definitely building on what was originally done in the Soviet Union.

Certainly, Greg Fahy has been involved in the conversation. He has been advising a lot, and my current understanding is that he is very optimistic about the promise of persufflation, which tells a lot about Greg. The fact is that if persufflation works as well as it’s probably going to work, it’s going to blow Greg’s last 20 years of work out of the water. It takes a lot of honor.

Yuri: Absolutely; Greg is an amazing scientist and human being. I think for him, just as for you, it’s all about defeating aging first, and everything else is secondary. In any case, do you have any other cryonics research planned as part of SENS or Arigos?

Aubrey de Grey: Not as part of SENS, but, of course, I talk to all these people all the time. Something that you might be aware of, which happened very recently, was that Alcor received a very large donation of 5 million dollars specifically for research from Brad Armstrong, one of the people who made plenty of money on cryptocurrencies.

Yuri: It’s great to see crypto millionaires donating money to longevity research.

Aubrey de Grey: Yes, 5 million dollars is a hell of a lot of money for research in cryonics compared to what’s been available up until now. I am actively helping Max More, CEO of Alcor, to decide how to spend it.

Yuri: That’s great to hear. Maybe we’ll get some research done on the restoration of brain activity after cryopreservation. I know that Greg Fahy has done some prior work on assessing LTP preservation, but it’s probably outside of the scope of our interview.

Switching topics, there’s a lot of talk about the biohacking community lately, and a lot of people call themselves biohackers these days. Some claim that taking supplements or working out qualifies as biohacking. Do you consider yourself a biohacker; do you take any supplements or nootropics like Ray Kurzweil or Dave Asprey or do anything else that could be considered as biohacking?

Aubrey de Grey: I don’t take any supplements; I don’t do anything special with my lifestyle. I am not saying that that’s my recommendation for other people. My situation is very strongly that I am prepared to listen to my body. I know that I am just a lucky guy. I am genetically built so that my aging is slow, and I am fortunate enough to have been tested for a total of five times now over the past 15 years; they’ve measured 150 different things in my blood and did all manner of physiological and cognitive tests. I always come out really well, way younger than I actually am, so I should be conservative: if it ain’t broke, don’t fix it.

I eat and drink what I like, and nothing happens. I will pay attention to the situation when it changes, but it’s not changing yet. There’s a couple of things that I do that are bad for my health, especially the fact that I travel so much that I am not getting enough sleep. I think I’ve been coping with that so far as well, and, of course, the reason I do this is to hasten the defeat of aging with all the work that I do. Maybe it’s a net win. The bottom line is that I’m lucky.

I don’t say that Ray Kurzweil is being dumb in doing what he’s doing. On the contrary, Ray is one of the unlucky people; he came down with Type 2 diabetes in his 30s, and his family has had a lot of cardiovascular problems. It probably makes sense for him to be taking all of these supplements in order to largely normalize his rate of aging. For somebody whose rate is normal or better, there’s no evidence that taking supplements could actually have any benefit.

Yuri: What about the cognitive enhancers that Dave Asprey is recommending? Have you ever found anything that works or that you have considered trying?

Aubrey de Grey: No, I let my brain do what it normally does. Even for jet lag or needing to go to sleep, I don’t need these things. I can get to sleep whenever I am tired, whatever time of day it is. I occasionally thought it might be good to have a stash of modafinil just to be able to get through times when I need to stay awake for a long time, but I managed to work my way around those periods, so I haven’t done that either.

Yuri: Maybe your brain is already overactive – I read that you do math problems for fun, and what was this preprint that you published that made a splash in the media?

Aubrey de Grey: I’ve always played with maths for fun. I am reasonably good with certain types of maths, especially those that don’t need too much background knowledge because I don’t even have a degree in maths like graph theory or combinatorics. Yes, earlier this year, I got lucky and made some progress on a very famous long-standing maths problem called the Hadwiger-Nelson problem, and that got a bit of attention. The thing that strikes me the most about all that is that a number of people said, “I always thought Aubrey de Grey was a bit of a lunatic and never paid any attention to what he said about aging, but now that he made progress in this maths problem, he’s obviously smart, so now I will pay attention to what he says about aging.” I think that’s the most fucked-up logic you can possibly imagine, but I’ll take it.

Yuri: From what I understand, despite your background in computer science and no formal training in biology, you actually also have a Ph.D. in biology for your work in mitochondrial respiration back in the 1990s. Is that correct?

Aubrey de Grey: Yes, that’s correct. I benefited from the fact that I’d done my undergraduate degree fifteen years earlier in Cambridge. Of course, that was in computer science, but there’s a system at Cambridge where if you do your undergrad degree there, then you don’t have to be a Ph.D. student to get a Ph.D. from Cambridge. You can just submit published work, it gets evaluated like a dissertation, and you do a thesis defense. Mitochondrial respiration was probably the first area in biology that I got interested in and that I was invited to write a book about, so I did. It included the material for the first six papers of mine, and that’s what I ultimately got my Ph.D. for.

Yuri: It seems that the mitochondrial theory of aging was all the rage back then but has lost a lot of its appeal over the past two decades.

Aubrey de Grey: Yeah, that’s a problem. The reasons why things move in and out of fashion in a biological field are often overly superficial. Nothing’s really changed. Twenty years ago, people were overly breathless about mitochondria and free radicals, and they were neglecting the importance of the shortcomings of those theories, which my first couple of papers helped to repair. I pointed out that you can’t just say “mitochondrial mutations matter because free radicals matter.” You’ve got to flesh it out, and I did flesh it out in a way that nobody else had bothered to do.

Conversely, what happened more recently is that people have swung the other way, saying “there’s various new evidence that free radicals don’t matter, therefore game over.” Again, they are being overly simplistic in the opposite direction. In fact, what this new evidence shows is that certain, particularly simplistic, versions of the free radical theory of aging are not true, but people like me who actually pay attention knew that all along. For me, nothing’s really changed.

Yuri: You make an excellent point that there seems to be some kind of fashion in the field of biology in general or aging research in particular. I wonder why; is it just human nature to jump on the bandwagon and reject all other ideas, or is it groupthink? What is it about science?

Aubrey de Grey: In science, I would say it’s even worse than groupthink. It’s not a question of people just being sheep because they can’t think for themselves. Scientists can think for themselves. The problem in science is that people are forced to follow fashion in order to get money, whether it’s in the form of a grant application, funding, getting promoted, or tenure, which is appalling, because the whole point of science is to go against the grain, to be in the minority of one as often as possible, and to find things out that people didn’t know before. However, the way that the scientific career structure these days actually works opposes that. It’s a tragedy.

Yuri: Indeed, the incentives for going against the grain seem to be misaligned. Is there any way to mitigate this?

Aubrey de Grey: The only solution is to throw a lot more money at science so that people can be career scientists in a way that they used to be 200 years ago when no scientists were without patrons, wealthy noblemen who kept them as pets. They were getting stuff done, and they didn’t have to worry about justifying how they were getting stuff done.

Yuri: Well, let’s hope some philanthropically inclined wealthy noblemen hear you and create more fellowships. Okay, final, semi-serious question: once humanity does reach negligible senescence, what would that do to relationships, family institutions, marriage, and children?

Aubrey de Grey: Nothing at all. The only things that would happen as a result of increased longevity are simply the continuation of societal changes that have already been occurring over the past century. What I see is that as people live longer and stay healthy longer, there’s a rapid increase in the number of divorces, the number of people who have multiple relationships over their lives, and it’s just going to be a continuation of that. It’s not interesting.

Yuri: And overpopulation is never going to be an issue, right?

Aubrey de Grey: This is the one that everybody is worried about, but it’s just so silly that people worry about it. I’ve been saying this since forever – and nobody contradicts my answer, they just ignore it – the answer is that the carrying capacity of the planet, the number of people it can sustain without a problematic amount of environmental impact, is going to go up much faster than the population can possibly go up even if we completely eliminated all death. It’s going to go up as a result of renewable energy, artificial meat, desalination, and all those things. It’s just so painfully obvious, and I’ve been saying this in so many interviews and so many talks, and people just ignore it. I think the only reason people are ignoring my answer is because they need to. They need to carry on believing that aging is a blessing in disguise and thus be able to put it out of their minds, get on with their miserably short lives, and not get emotionally invested in the rate of progress that we will make.

Yuri: Well, let’s hope we can shake them out of their learned helplessness in the face of death and aging.

Aubrey de Grey: Absolutely.

Yuri: Great, thank you so much for this interview! I really look forward to seeing you in Moscow soon and discussing some of these issues in person as well as hearing about your latest achievements in the fight against humanity’s biggest problem!

Aubrey de Grey: Indeed! Thanks so much, Yuri, it’s been great.

Yuri Deigin is a serial entrepreneur and an expert in drug development and venture investments in biotechnology and pharmaceuticals. Yuri brings almost a decade of drug discovery and development experience from his previous role in a biotech startup where he oversaw research and development of original medicines aimed at treating diseases like Alzheimer’s and rheumatoid arthritis. Yuri has a track record of not only raising over $20 million for his previous ventures but also initiating and overseeing 4 clinical trials and several pre-clinical studies, including studies in transgenic mice. He also has experience in pharmaceutical product launch, promotion, manufacturing, and supply-chain management. Since 2013 Yuri also serves as a vice-president of the non-profit Foundation “Science for Life Extension” whose goal is the popularization of the fight against age-related diseases. To further this cause, Yuri frequently blogs, speaks, writes op-ed pieces, and participates in various TV and radio shows. Yuri holds a B.Sc. from the University of Toronto and an M.B.A. from Columbia Business School. Yuri is the CEO of biotech company Youthereum Genetics.

U.S. Transhumanist Party Chairman Gennady Stolyarov II Answers Common Interview Questions

U.S. Transhumanist Party Chairman Gennady Stolyarov II Answers Common Interview Questions

Gennady Stolyarov II


Gennady Stolyarov II, Chairman of the U.S. Transhumanist Party and Chief Executive of the Nevada Transhumanist Party, answers questions posed by Francesco Sacco, which are representative of common points of inquiry regarding transhumanism and the Transhumanist Party:

1. What is Transhumanism and what inspired you to follow it?
2. What are the long-term goals of the Transhumanist party?
3. What are your thoughts on death and eternal life through technological enhancements?
4. Do you feel there are any disadvantages to having access to the cure for death? What advantages are there?

Become a member of the U.S. Transhumanist Party for free, no matter where you reside. Fill out our Membership Application Form here.

See Mr. Stolyarov’s presentation, “The U.S. Transhumanist Party: Pursuing a Peaceful Political Revolution for Longevity“.