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Steve Hill Interviews Sarah Constantin of The Longevity Research Institute

Steve Hill Interviews Sarah Constantin of The Longevity Research Institute

Sarah Constantin
Steve Hill


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

~Bobby Ridge, Assistant Editor, June 30, 2019

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

Searching for longevity

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

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

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

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

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

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

Replicating and Extending Lifespan Results

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

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

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

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

Best practices and transparency

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Steve Hill


Editor’s Note: The U.S. Transhumanist Party features this article by our guest Steve Hill, originally published by the Life Extension Advocacy Foundation (LEAF) on August 27, 2018. This article takes another step forward toward clearing up a common misconception that many scientists and laypeople hold, i.e., the notion that extending telomeres causes cancer. Mr. Hill cited a recent article published in the journal PLOS Genetics, in which researchers found there to be no increase in cancer, even when telomeres were extended in mice from cancer-prone mouse strains. Hopefully this article will help researchers reevaluate this misconception so this very important age-reversal research will be advanced much faster.

~ Bobby Ridge, Assistant Editor, June 20, 2019

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

A tale of telomeres

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

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

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

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

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

Abstract

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

More support for telomerase gene therapy

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

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

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

The road ahead

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

Conclusion

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

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

Literature

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

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

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

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.

A Biohacker’s Letter to Santa – Article by Elena Milova

A Biohacker’s Letter to Santa – Article by Elena Milova

Elena Milova


Editor’s Note: Happy Holidays! If Santa Claus were real, life extension would be the greatest gift that he could possibly give. Elena Milova convincingly illustrates why in this letter, originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Gennady Stolyarov II, Chairman, U.S. Transhumanist Party, December 21, 2018

Dear Santa,
My name is Elena Milova, and I am from Moscow, Russia. I am a science popularizer, biohacker, and public health advocate in the field of aging and longevity. I am 39, single, and without children, but if you think that I am reaching out to you to ask for a CRISPR-designed baby, I am not. I believe that this type of wish is rather in the pile of letters from China. I am not asking you for a particular health improvement, as one could not wish for a better HOMA-IR (mine is 0.40, because I greatly reduced fast carbs) or total cholesterol level (below 4 mmol/L). I am fine without a new smartphone, too.

The thing that I am going to ask you for is much more tricky to get. I want everyone on Earth to realize that biological aging is amenable to medical intervention and that treatments targeting various mechanisms of aging are already in human clinical trials. 7.6 billion minds, one idea. That is my only wish.

Why this is so important to me

You have probably noticed yourself that your clientele is changing over time. There are more and more people over 60 in the world, and I assume that the number of wishes for recovery from this or that age-related disease are spiking higher every year. This must be a problem for you, as for many diseases of old age, there is still no effective treatment that would actually help to cure people. It must be frustrating to not be able to fulfill a sincere wish of a good person, especially when a child asks for her grandparents to recover so that they can walk and throw snowballs together.

Source: United Nations, Department of Economic and Social Affairs, Population Division (2017). World Population Prospects 2017 – Data Booklet (ST/ESA/SER.A/401)

By 2050, the elderly will be a quarter of the global population, and these people will likely be suffering from several chronic diseases at once, gradually losing their health, independence and dignity. For so many people, being a burden on their families because of their deteriorating health is unacceptable, which is why the number of suicides in this age group is so high.

Is aging an invisible problem?

The numbers of these voluntary deaths are very upsetting, but what is even more upsetting is that diseases of old age are the major cause of death worldwide and aging kills around 100,000 people every day. This is the population of a small city. Imagine what would happen if everyone in a city like Cambridge, Massachusetts were to die in one day. I bet that there would be a lot of media attention and that thousands of experts would be on television discussing the potential causes of death and ways of preventing this tragedy in the future. Let’s say that the next day, another city becomes deadly peaceful. Take the Russian city of Domodedovo, which has its own airport. Everyone dead. People in neighboring cities would probably be frightened, and some charismatic politicians would be trying to calm down the public and promising to do something about all these deaths. The next day, this happens to yet another city, maybe in India. Then another one in Australia. It would not take long before G20 would set up an urgent conference call to set up an international commission and allocate money and scientists to investigate and solve the problem.

                                                                                                                                              Source: WHO website

Guess what? This type of thing never happens in relation to aging, because people dying from it are spread around the globe, so the disaster does not make the headlines. The public only notices the problem when an actor, scientist, or other significant public figure dies from an age-related disease – most often heart disease, stroke, or cancer. Do you want an example? “Santa Claus, age 90, dies from a heart attack: a critical blow to the industry of giftmaking.”

Sorry, sorry. I didn’t mean to scare you, but you get the point, right? From looking at your pictures, I could suspect that you might have some minor problems with glucose metabolism, but your extensive physical activity during gift delivery should be compensating for that, so you should be fine. For other people aged 60 and older, aging is an ever-increasing problem. Here, we come to the other important issue.

What is aging? How it can be addressed?

You see, aging is the accumulation of damage that happens due to normal bodily functions. This damage builds up over time, normal cell functions erode, and, at some point, this leads to the manifestation of age-related diseases. Normal operations, damage accumulation, disease, more damage, aggravation of disease, death. Simple.

It turns out that at the beginning of this century, British scientist Aubrey de Grey published an article in which he described several types of damage done by aging. He suggested the heretical idea of targeting these damages with medical interventions instead of trying to cure the symptoms of each age-related disease. He argued that age-related diseases are only a consequence of damage accumulation and that it would be much more effective to address the root causes.

The seed that Dr. de Grey dropped into the fertile soil of scholarship produced nice fruit in 2013, which is when a group of famous researchers of aging published The Hallmarks of Aging, a paper in which they described nine types of damage that accumulate with age and could be made into new therapeutic targets.

Comparison of a mouse treated with senolytics (at right) and a same-age mouse of the control group (at left). Source: Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., … & Khazaie, K. (2016). Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature, 530(7589), 184.

There were other fruits as well: animal studies have definitively proven that even only addressing one type of damage can extend the healthy period of life, postpone age-related diseases, keep animals more active, and, as a positive side effect, extend lifespan. It is worms that hold the best record so far, as tweaking some of their longevity-related genes has allowed them to live 10 times longer. The results in mice are also impressive – the researchers can extend both their healthy period of life and lifespan by 30-35%. Honestly, I find myself jealous of these mice, sometimes. I would not mind adding another 30% of youthful and healthy years to my life, even if I would have to take some pills or get some regular injections.

Can we control aging in humans?

You see, Santa, where I am going with this. I am sure that you sometimes leave gifts under the trees of people who work for the FDA. Accumulating a critical mass of knowledge about interventions against murine aging made it possible to develop the same type of interventions for people. Now, drugs and therapies addressing some of the root mechanisms of aging are in official human clinical trials. At some point, some of these trials will be successful, and drugs and therapies targeting aging itself will come to market.

If you don’t believe me, here is the short list of people whose chimneys’ stacks are the best source of additional information on the topic: George Church, Anthony Atala, Judy Campisi, Vadim Gladyshev, Maria Blasco, Michael West, Vera Gorbunova, Irina Conboy, Kelsey Moody, Brian Kennedy, Linda Partridge, Alexey Moskalev, Cynthia Kenyon, Claudio Franceschi, Alex Zhavoronkov, Nir Barzilai, and, of course, Aubrey de Grey. He wears a great beard, so you have more in common with gerontologists than you would think.

Listen to these people tell their families about their research, and you will get my point. We are on the edge of a revolution in rejuvenation biotechnology. Yet, most people don’t know about it and don’t realize what kind of potential benefit this advancement holds for them and for our aging society as a whole. Most importantly, as they know nothing, they have no say in decision making. How can people possibly speed up the pace of aging research if they don’t realize that aging is amenable to intervention? How can they foster technology transfer and local production of the cures for aging, such as senolytics, in their countries? How can they control prices and make future distribution and access equal? How can they ensure that old people in their families, who need these new treatments the most, would get them sooner?

Knowledge is power. We hear this in almost every interview, and you should be hearing it every Christmas from the researchers of aging, too. They have golden brains; the only thing they need is an appropriate amount of funding to solve the problem of aging more quickly. A strong public movement for aging research could be a game changer and could act as leverage to allocate government funding towards researching and developing treatments that target the underlying mechanisms of aging.

Ending aging and age-related diseases is possible

It is obvious that you are a kind person, Santa. You are perceptive and generous; you know what people want, and you try to give them what they want. However, if you don’t help me with my information campaign, in a couple of decades from now, you will be delivering billions of adult diapers and wheelchairs all over the globe. Wouldn’t it be nicer if you were to pile these up in your warehouse to be covered in dust while you give people therapies and drugs that prevent aging and wipe age-related diseases out of human lives? Just imagine how much happier people would be if they could remain healthy and independent, enjoy full and productive lives, achieve more, and stay with their families and friends for longer.

I was a good girl the whole year, attending scientific conferences, interviewing researchers, speaking at public events, and supporting our partners and colleagues in every way I could, even if that much socializing makes me suffer from an introvert’s hangover. I was eating healthy food and promoting evidence-based means to slow down aging among my relatives and friends. I deserve a nice Christmas gift.

All you have to do is to let everyone on the planet know that aging is amenable to intervention and that treatments addressing the root causes of aging are currently being created. For real. That would make me the happiest creature on the planet. Thank you in advance!

Sincerely, Elena

Instead of a conclusion

I am 39 years old, and I am an agnostic. There is not much evidence that Santa Claus exists. However, I do believe that miracles happen: the miracles that we create with our own hands. You who are reading these words (thanks for getting this far, by the way!) possess this special power, too. Use it! Let people around you know that science is close to bringing aging under medical control, and let’s build a world where healthy longevity for everyone is a reality.

As a devoted advocate of rejuvenation technologies since 2013, Elena Milova is providing the community with a systemic vision how aging is affecting our society. Her research interests include global and local policies on aging, demographic changes, public perception of the application of rejuvenation technologies to prevent age-related diseases and extend life, and related public concerns. Elena is a co-author of the book Aging prevention for all (in Russian, 2015) and the organizer of multiple educational events helping the general public adopt the idea of eventually bringing aging under medical control.

Fifth Enlightenment Salon – Discussions on Longevity, Gene Therapy, Overcoming Disabilities, Animal Lifespans, Education, and Privacy

Fifth Enlightenment Salon – Discussions on Longevity, Gene Therapy, Overcoming Disabilities, Animal Lifespans, Education, and Privacy

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Gennady Stolyarov II
Bill Andrews
James Kohagen
Bobby Ridge
John Murrieta


On October 13, 2018, in the spirit of the Age of Enlightenment and its furtherance today, Gennady Stolyarov II, Bill Andrews, James Kohagen, Bobby Ridge, and John Murrieta met for the fifth interdisciplinary discussion – hosted by Mr. Stolyarov – on science, culture, education, advocacy, and policy. Subjects discussed included the following:

– The recent RAAD Fest 2018 in San Diego
– Developments in the field of gene therapy
– Advances in epidural stimulation for treating and overcoming spinal-cord injuries
– Long-lived organisms and their similarities and dissimilarities to humans
– How animal experiments can become more humane
– How contemporary science still has far to go to accumulate even fairly basic information about certain organisms
– How the study of lifespans can be included in educational curricula starting at early childhood
– Whether privacy will remain in a more technologically interconnected future.

Join the U.S. Transhumanist Party for free, no matter where you reside by filling out an application form that takes less than a minute.

Find out about Death is Wrong – the illustrated children’s book on indefinite life extension.

“Squeak” – Art by Laura Katrin Weston, a.k.a. Katrin Brunier

“Squeak” – Art by Laura Katrin Weston, a.k.a. Katrin Brunier

Laura Katrin Weston




Commentary by Gennady Stolyarov II, Chairman, United States Transhumanist Party: “Squeak” is a print by Dr. Laura Katrin Weston, a.k.a. Katrin Brunier, the original exemplar of which I received in November 2017 due to my donation to the successful MouseAge crowdfunding campaign by Lifespan.io.

It is fitting for a project on mouse longevity to involve at least one image of mice – creatures whom life has unfortunately dealt a bad hand, due to their short lifespans (only 3 years for even long-lived mice in the absence of medical intervention), difficulty in getting along with humans, and unnecessary attrition due to disposal practices after lab experiments. “Squeak” invites the viewer to appreciate mice a bit more; if we can extend their lives significantly, we stand a decent chance of achieving dramatic extension of our own lifespans.  Perhaps we can also give some of the mice a break by using photographic markers of aging in experiments, as the MouseAge project seeks to do.

Here, the mice are depicted scurrying along a narrow circular path. The golden circle, with rays emanating outward represents perhaps the great hope that these creatures unknowingly provide to us. One may wonder, as I have done over many months of reflecting on this work, whether these are mutant, two-tailed mice, or whether they each just have their ordinary curly tails, and the track along which they move might simply be painted in the same colors and textures as their tails. (Well, in actuality it is indeed painted that way!) Mutant or not, these mice are rather extraordinary in having become emblems of a species that has added much to our understanding. Unlike most of their brethren to date, these mice have earned their extreme longevity through Laura Katrin Weston’s brush.

You can find more work by Dr. Laura Katrin Weston at the Katrin Brunier Gallery, an Ethical Investment-Grade Art Gallery for the Neo-Renaissance Era (see its Instagram page). Proceeds from art sales at the Katrin Brunier Gallery will go to support causes such as medical research and conservation.

Being Excited About Failure – Article by Martin van der Kroon

Being Excited About Failure – Article by Martin van der Kroon

Martin van der Kroon


The much hyped CRISPR-Cas9 genome-editing technique often explained as being the ‘DNA scissors’ or the ‘cut and paste’ technique, has had a setback, and this has me excited.

CRISPR-Cas9 has has the scientific community, and in particular those involved in research and development of genome editing, raving over the roughly past 3 years. It is hailed as a cheap and fast way to edit genomes with great accuracy compared to other genome-editing techniques, and this is true. Now however, researchers have found CRISPR-Cas9 to have some annoying side-effects. The side-effects were found in mice who had their blindness corrected but also caused mutations in other parts of the DNA sequence, roughly 1500 mutations. It is unknown what the consequences of the mutations are at this moment.

“Why am I excited about this setback?” you might ask.

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