All posts by didiercoeurnelle

The Death of Death Fertility, longevity & menopause. N° 144 March 2021

The law is already strict on rapamycin and metformin, requiring a prescription. In comparison, alcohol and tobacco do not require a prescription or medical supervision. Smoking has no health benefits and dramatically reduces life span, accelerating all diseases. While smoking causes cancer, rapamycin prevents it, including smoke-induced lung cancer. Is it then paradoxical that alcohol and tobacco are sold without prescription, while rapamycin and metformin are not. 

Blagosklonny M. V. The goal of geoscience is life extension. Oncotarget. 02 February 2021; 12: 131-144


Theme of the month: Fertility, longevity & menopause


While men are fertile every day, women’s fertility is cyclical. In fact, most girls are born with a certain stock of oocytes from birth, and even a little before. This stock varies between 300,000 and 500,000, of which an average of 400 will actually mature. From puberty onwards, an oocyte is released at each cycle and then eliminated by menstruation when there is no fertilization and over the years, this stock of oocytes decreases. 

And when they’re gone… they’re gone… It marks the end of a woman’s fertility cycle and the arrival of menopause!

Nature is such that, spontaneously, around the age of 50, a woman’s body undergoes a major hormonal change. The health consequences attributed to this change are multiple and variable, both in frequency and in severity. Symptoms include climacteric disorders (hot flashes, chills, feelings of discomfort and dizziness, etc.), mood and sexual disorders (decreased libido, pain during sexual intercourse, vaginitis, etc.), as well as an increased risk of cardiovascular disease and osteoporosis.

When the ovaries quit …

However, for some women, menopause strikes very early. Even before blowing out 40 candles, their lives are turned upside down. A report published on the American website Health explains the 5 reasons why some women are subject to early menopause. Among the factors influencing the age of menopause, there is the genetic factor. In 20% of the cases, a woman who went through menopause very early was not the only one in her family to suffer from this problem. Certain treatments such as chemotherapy and radiotherapy can also affect the genetic material of ovarian cells. But not only that, smoking and being overweight can also be responsible. Several studies state that on average, menopause occurs 2 years earlier in smokers. On the other hand, an overall improvement in diet, hygiene and quality of life in Western countries has put off the average age of menopause.

And among the animals?

Menopause seems to be unique to women… and to cetaceans. This early cessation of reproduction is rare in the animal world. On Earth, only women and four other animal species (the beluga, the narwhal, the killer whale and the pilot whale) experience menopause, a phenomenon among mammals that intrigues scientists. For example, female orcas can expect to live to over 90 years of age, but astonishingly they reach menopause between the ages of 30 and 40. 

But why should a female stop reproducing before the end of her life? This physiological cessation is often described as an evolutionary paradox, as it appears that females derive no benefit from ending their reproductive careers well before death. In a recent study published in Scientific Reports, conducted by researchers from the University of Exeter (UK) and the Center for Whale Research (USA), Dr. Samuel Ellis explains that « For menopause to make sense in evolutionary terms, a species needs both a reason to stop reproducing and a reason to live afterwards”.

The British researcher suggests the « grandmother effect » as an explanation. This hypothesis had been formulated by the anthropologist Kristen Hawkes and her colleagues to understand why menopause occurred during the evolution of humanity. Menopause would have been selected by natural evolution to allow females of very sociable species with a long life expectancy to devote themselves to their direct offspring and those of their children without running the risk of dying during a late pregnancy. After a few generations, a post-menopausal female will therefore have passed on her genes to more offspring than a female who has continued to give birth.

In tribes of hunter-gatherers, it has been found that the chances of survival of the young until the age of reproduction, is positively correlated to the presence of one or two of their grandmothers, certainly because they relieve the mothers in the burdens of child-rearing.

Inmost animals, as in our pets (dogs, cats, mares, cows…), we observe that over the years, the cycle becomes more irregular, that fertility decreases and health concerns can appear because of the drop in sexual hormones, but we cannot call this a real menopause.

Paradoxically, this phenomenon does not exist in any primate. Our closest cousins can become pregnant until the very end of their lives because their reproductive organs slow down with the rest of their bodies. Chimpanzees can remain reproductively viable for more of their lifespan than women. Although research published in 2011 on captive chimpanzees indicates that females go through menopause in their final years.

More surprisingly, in elephants we observe this « grandmother effect » which may explain the usefulness of menopause. However, the females can reproduce until the end of their lives. Scientists do not yet know why cetaceans have a menopause and elephants do not. More studies are needed to solve the mystery…

Birds do not experience menopause either. Some can remain fertile for a very long time. Wisdom, a female Laysan albatross defies nature. The oldest wild bird in the world had a chick at the age of 70! 

Pregnancy after 50? Is it possible to reverse menopause? 

Menopause can be considered either as a natural part of aging or as a pathology that needs to be treated.

It is often said that pregnancy after menopause is impossible. However in 2016, scientists at the Fertility Clinic in Athens managed to reverse the menopause process in a 45-year-old woman even though she had been menopausal for 5 years! 

The scientific team injected the ovaries of about 30 menopausal women with platelet-rich plasma (PRP). It is widely used to speed up the repair of damaged bones and muscles. The women who received the PRP treatment were all between 45 and 49 years old and had not had a period for several months. Six months after receiving a PRP injection, the 45-year-old woman noticed her period returning. The newly released eggs can be collected and fertilized in vitro. This offers a new window of hope for women suffering from early menopause.

In 2020, Dr. Konstantinos Pantos and his scientific teams obtained even more astonishing results: menopausal women gave birth after a PRP injection! Their fertility is said to have been restored thanks to the PRP treatment. Among the 30 menopausal volunteers, four became pregnant and three had children.

Cryopreservation to delay menopause by 20 years! 

This is at least what specialists in in vitro fertilization in Great Britain affirm. Their method has already been tested on nine women. The procedure consisted of taking ovarian tissue which is then frozen to be preserved. Later on as they enter menopause, the frozen tissue can be defrosted and transplanted back into the body to restore declining hormone levels. 

However, experts believe that it is possible to delay the onset of menopause by up to 20 years, but this depends on the age at which the tissue is removed and when it is put back in. For example, tissue taken from a 25-year-old woman could delay menopause by 20 years, while tissue taken from a 40-year-old could delay its onset by only five years.

Conversely, some beauty products bring forward the age of menopause…

According to Dr. Amber Cooper and her team (United States), exposure to chemical molecules, contained in particular in beauty products, can advance the age of menopause by 4 years. Between 1999 and 2008, they conducted blood and urine tests on 31,500 women to check for the presence of chemicals. The researchers found that women with high levels of chemicals in their bodies went through menopause 1.9 to 3.8 years earlier than women with lower levels.

The value  of rodents in the fundamental understanding of key elements in the reproductive and aging processes… 

We wrote earlier that only a few animals experience menopause. However, rats (and mice), at least in the laboratory, gradually cease to be fertile well before their maximum lifespan. Indeed, a rat can live more than three years, but its fertility decreases sharply after 10 months.

As we have seen, the effect of platelet-rich plasma (PRP) has had a positive effect in postmenopausal women in Greece.

In 2018, scientific teams wanted to evaluate the effect of PRP on ovarian structures and function in cyclophosphamide (Cy)-induced ovarian failure in female rats using a stereological method. The researchers concluded that it appears that PRP has a protective effect on ovarian failure in the infertile female rat model.

Rats and mice are imperfect but extremely useful models to better understand and combat the mechanisms of aging. However, to be certain of the effectiveness of a treatment, the maximum lifespan with or without treatment must be compared. This can take a long time since a rat can live more than 3 years. 

By examining the fertility of rats with anti-aging treatments, the information in the laboratory can be obtained much faster. An « ordinary » laboratory rat is 6 months old when experiments begin. After only 4 months of treatment, it will be possible to see if treated rats, compared to control rats, remain more fertile and therefore age less.

It should be noted that longevity experiments are done with a much more pleasant treatment of the animals than the life of sewer rats. This can be explained by the demanding protective legislation and because the goal is to make them live longer, good treatment favors it.


The (relatively) good news of the month:

 The fight against Covid through vaccination is making progress  


To speak of good news about this disease is very relative. There are nearly 3 million deaths recorded. New mutations are appearing more and more. The fine declarations concerning the vaccine, a common good of humanity, have been followed by little effect. Collaboration across financial, social and political barriers is difficult. Finally, populations are exhausted by restrictive measures.
But all is not bleak. By the first quarter of 2021, a big year after the pandemic broke out, more than 100 million people worldwide will have been vaccinated. About 10 vaccines are now being administered worldwide. The vaccines seem to be effective against the different variants of the disease.

As the elderly are the first victims, they are also very often the first to be vaccinated. Never in the history of mankind have we been so concerned about the weakest people in society and about research on this subject.  This is progress for all of humanity. Finally, the realization that Covid is just one of the many age-related diseases is gradually growing. And research to end Covid is sometimes extended to research against other age-related conditions.


For more information:

ALL ABOUT PEOPLE 2021: Digital Transformation in Science, Education and Arts (Slovenia) March 12 to 19, 2021.

9th Scientific Conference with International Participation under the auspices of the President of the Republic of Slovenia, Mr. Borut Pahor

The conference All about people 2021 is dedicated to the topic of digital transformation in science, education, and arts. With the arrival of COVID-19, the changes that had already taken place in the educational process, have only accelerated unexpectedly with the rapid development of new technologies.

This event will take place online from March 12 to 19, 2021.

the conference schedule is online http://submission.almamater.si/mobile/#s:64 

The Death of Death N° 143. Longevity, amortality, transhumanism, technoprogressism. February 2021

…will we be able to live forever remains an unanswered question; turning a hundred years old into the new sixty – that is significantly extending human lifespan – has changed from a question of « if » to a matter of « when ». Peter Diamandis, entrepreneur, engineer, futurist. Page 179. The Future Is Faster Than You Think.


Theme of the month: Longevity, amortality, transhumanism, technoprogressism


It is one of humanity’s oldest dreams, health without any time limit. We all wish each other this in the New Year. Good health. We know more and more about why and how aging occurs. But we still cannot control senescence.

Not all those who wish to go beyond our biological limits, beyond 100 years of life, will define themselves as transhumanists. On the other hand, almost all transhumanists will describe themselves as longevitists.

What is longevitism?

It is the search for a much longer life, beyond what is possible today, thanks to advances in science and medicine.

Longevitism arouses both attraction and opposition. The opposition isoften motivated by the fear of false hopes, the fear of living longer but in poor health and the fear of therapies only for the rich. 

Longevitists want research for a healthy life, based on serious scientific evidence and are generally attentive to broad accessibility.

Their research may be moderate, aimed at and only a few more years of good health. It can be strong, aiming for a life of well over 120 years.

So the goal of these therapies is to strongly reduce or even eliminate the mechanisms of senescence. The most optimistic will aim at what is called « biological immortality« , the absence of any aging mechanism. The term « amortality » is also used.

What is transhumanism?

Let’s take Wikipedia’s definition: it is a philosophical movement that advocates for the transformation of the human condition by developing and making widely available sophisticated technologies able to greatly modify or enhance human intellect and physiology.

The word transhumanism sometimes frightens people because it evokes the appealof dangerous, dehumanizing technologies. The vast majority of transhumanists are aware of the dangers linked to technical progress. They actively wish for technologies to reduce risks, especially the so-called « existential » ones, to increase resilience and thus the quality and duration of life.

The improvements that transhumanists aim for can be physical: higher, stronger, further, more adapted to the environment. It can be related to the sense organs (better sight, smell, new sensory capacities…). The improvements aimed at can also be related to intellectual capacities. The goal is then to allow more intelligence, more capacity for empathy, compassion, happiness …

But the improvement most often envisaged by transhumanists is that of the improvement of life expectancy, thus the objective of longevitists. This is the necessary, but not sufficient condition for all other increases, for all human rights. Without sustainable life, there are no rights, no possibilities.

What is technoprogressism?

Technoprogressism is a transhumanism for which the idea of linking technological and social progress is central. When we look at the history of humanity, we see that technological progress has largely contributed to social progress and vice versa. But this is not automatic. Technoprogressists will insist on accessibility to technological progress for all those who want it. This applies in particular, of course, to health and longevity therapies.

One of the main founders of transhumanism, Briton David Pearce, summarized transhumanism by 3 S’s: Superlongevity, Superintelligence and Super well-being. Technoprogressists sometimes add « Super democracy » or Supersocial.

Biological » longevity and « computer » longevity.

For most contemporary longevitists, the ultimate goal is a much longer life with an « ordinary » body, not so different from the contemporary body.

This concept of « ordinary body » must be put into perspective. We already accept today many things that would have appeared totally unnatural even to the most erudite two centuries ago. We transfuse blood, we almost all have foreign bodies in our mouths. At the end of our lives, most of us will have gone through a physiological state that does not exist outside of medicine, somewhere between sleep and death. We call it general anesthesia. Millions of humans have been conceived in a test tube. Millions of us also have pacemakers, cochlear implants… In fact, what yesterday was unimaginable transgression is today medicine. And today’s transhumanism could be tomorrow’s medicine.

But for some more radical transhumanists and longevitists, we could go far beyond our biological composition. Man-machine « fusion » could develop, concerning an increasingly large part of the body, creating a cyborg. Further still, one day, human consciousness could become independent of the body, be transferred onto a computer medium. This vision was discussed in a letter in 2012. It remains today totally hypothetical within a reasonable timeframe. For most longevitists, and probably also for most transhumanists, this could only become possible where computers reproduce biological processes as well as or even better than the processes themselves.  Where the virtual copy would be better than the original. Like a beautiful film can be more beautiful than reality. Like a game can be more enjoyable than the situation that gave birth to it.

This requires nanotechnology and computer efficiency far beyond current capabilities. Above all, it implies being able to understand and replicate the neural mechanisms of what is often defined as « the most complex object in the known Universe« .

Longevity, transhumanism, artificial intelligence

The IT of the near future is above all the development of an increasingly strong artificial intelligence, developed to facilitate human interests. Longevitists, transhumanists or not, hope, and try, to implement computing processes allowing better and faster research. An acceleration of discoveries for health, longevity and resilience also requires massive data that is easilyaccessible and well organized.

Using research capabilities primarily for these purposes, rather than for competitive, military or consumer purposes, is likely to reduce the risks associated with artificial intelligence. Making the best « brains », both human and computational, work together for a much longer healthy life will reduce the risks of developing intelligence that is far removed from human beings.

This is important because the risks of an artificial intelligence « turning radically wrong » are considered high by many. Among those who are concerned, there are many transhumanists, including Nick Bostrom, author of a renowned book on the subject.

More human, tomorrow

Longevitists generally focus first on medical progress and everything that contributes to it. Transhumanists, especially technoprogressists, also seek to analyze why this progress is important. They will explain that a much longer life will make it possible to have

– a more peaceful life, with less violence and more caution;

– to love each other more and to stress us less, since we will have more time;

– to be more careful about the biosphere because we will know that we are here for the long term. A sustainable body is not possible without a sustainable planet.

Less overpopulation, and more attention to children. For it is where life is longest that children are the rarest and that we have the most time to devote to them.

For these and other reasons, the age-old quest for the Fountain of Youth is today a more desirable and reasonable goal than ever. Today, we still have to accept death from old age because we have no choice. Tomorrow we may choose.


This month’s good news: Conference and workshops on February 11, 2021 on animal and human testing for longevity. Support from Heales for two studies testing the lifespan of rats treated with young plasma.


The February 11th conference on the topic « Clarifying whether and to what extent current anti-aging approaches work in mice or people » was a great success with more than 100 participants.

Present were specialists on the subject such as Irina Conboy, Nir Barzilaï, Greg Fahy and Liz Parrish to name but a few. If you wish to discover them all, the conference split up by speaker remains accessible.

A synthesis of the proposals made during the workshops has been produced.

Since the beginning of 2021, the Heales association has been supporting two studies, carried out by Rodolfo Goya in Argentina and Harold Katcher in India, each following the maximum lifespan of rats treated with blood products, in order to verify the beneficial effect on longevity of this type of treatment.

If significant longevity results are not achieved, this will « close a door ». If important longevity results are established, this will be extremely important news. The conviction of most researchers and the association is that the first hypothesis is the right one. But we would love to be proved wrong!


Find out more:

The Death of Death. Will something that doesn’t kill you make you stronger? Hormesis. N° 142 January 2021

I mentioned (…) the work of the 2009 Nobel Prize winners, Blackburn and Greider (…), who, in their press conference on telomerases, told us:  (…) We will live between 300 and 600 years. I say this in front of an audience of bosses who burst out laughing. (…). Would you take these capsules? Of course I would take them. Of course I would! Roselyne Bachelot (former Minister of Health) in 2016. Why does Google want to make us immortal? 


Theme of the month: Will something that doesn’t kill you make you stronger? Hormesis.


Hormesis (also known as  preconditioning, conditioning, pretreatment, cross tolerance, adaptive homeostasis, and rapid stress hardening) is a biological principle that allows us to naturally improve the functions of our body, its resistance, its immunity… It is a valuable aid in fighting the adverse effects of aging.

It is a particularly topical subject given the importance of good immune defenses to avoid or limit the impact of viral infections. Still poorly characterized, hormesis has been the subject of numerous scientific studies over the last twenty years.

Hormesis: how does it work?

Basically, hormesis is a stimulation of the biological defenses of an organism in response to a low dose of toxins or other stress-generating agents. This exists in all living beings, starting with the single cell.

In practice, the rule is simple: Subject your body to an optimized level of  stress, typically of short duration, followed by a period of rest and recovery, and it will strengthen itself, to adapt and better resist next time. This illustrates Nietzsche’s quote: « What  does not kill, makes you stronger« .

This stress can be a toxic substance, an exposure to extreme temperature or radiation, unusual muscular effort, physical or psychological constraints, deprivation of nutrients or oxygen, or other factors that directly affect the functioning of cells.

The paradoxical consequence of hormesis is that the increased comfort of our daily life does not always improve our health. For example, permanent environmental comfort, sanitized food, motorized travel, aseptic environment… Our modern comfort can weaken us. 

First of all, hormesis improves our functions of adaptation to the environment and to external constraints: regulation of body temperature, muscular resistance, use of nutrients, production or storage of energy within our cells…

Moreover, it strengthens other major vital functions (circulatory, immune, repair, nervous…). 

It is important to  not confuse short-term stress, rather beneficial, with chronic stress which accentuates aging and often leads to illness (especially permanent psychological stress, which is common nowadays).

Below there is  an illustration of the phenomenon. Under a certain threshold, the stimulation by stress is too weak to induce a strengthening of the organism, conversely above  a second threshold, there is a risk of toxicity or degradation.

The « hormetic zone » varies from one individual to another and depends in particular on their physical and psychological state of fitness.

The dose (or intensity) of a biological stress or nutrient is essential in determining whether it will have beneficial or toxic effects. Paracelsus’ famous quote from the 16th century « All is poison and nothing is without poison; only the dose makes something not poison » was completed in the 19th century according to Arndt-Schulz’s law: « For any substance, low doses stimulate, moderate doses inhibit, too high doses kill« .

Until now, it is not completely understood how hormesis can increase life span. Many so-called « anti-ageing » processes do, in fact, act through the mechanism of hormesis (e.g. caloric restriction or rapamycin).

Does hormesis apply to any substance or toxic action in high doses? Probably not. For example, for hormone disruptors, studies seem to show that there is an accumulation of toxic effects even at very low doses.

Phytochemicals in plants

Phytochemicals such as alkaloids, polyphenols and terpenoids activate the same processes as caloric restriction, fasting and exercise. Many of the beneficial effects of fruits and vegetables may therefore be due to the activation of stress resistance pathways by substances that plants secrete to protect themselves.

Caffeine, EGCG (green tea), curcumin, glucosamine, polyphenols, polysaccharides, quercetin (onion), resveratrol (grape and wine), spermidine (soy, mushroom) and sulforaphane (broccoli) are molecules that produce hormetic effects.

For example, a low dose of sulforaphane protects cells from oxidative stress, a higher dose of this compound has toxic effects on cells that lead to cell death. Similarly, a low dose of resveratrol (2 mg/kg) reduces inflammation-induced stomach ulcers in mice, while higher doses (5 and 10 mg/kg) increase the formation of ulcers and markers of inflammation.

Hormesis and pollutants

PFAS chemical molecules, also known as perfluorinated pollutants or eternal pollutants, are part of our daily life. It has been shown since the 2000s that these elements contaminate ecosystems, even in areas far removed from human activities, such as the Arctic regions.

However, a study by the Center for Biological Studies in Chizé and its Norwegian partners has shown that exposure to these pollutants is associated with lower telomere erosion and increased survival in a seabird from this area. These surprising results were published in July 2020. This study is the first to make the link between telomeres (a significant mechanism of ageing)  longevity and contamination by these pollutants, which are increasingly present in the Arctic.

Hormesis and radiation

According to the hypothesis of radiation hormesis, low doses of radiation can stimulate the activation of repair mechanisms that protect against disease and that are not activated in the absence of ionizing radiation.

Low dose here means small additional doses comparable to normal background radiation (10 µSv = average daily dose from the natural background). Since at high doses the negative effects are irrefutable, there must be a threshold between the beneficial and negative effects of radiation. This threshold is known as the Zero Equivalent Point (ZEP).

Hormesis and increased immunity

Our immune system strengthens with repeated exposure to microbial agents (for example, children playing in the dirt have fewer infections than those living in a more « sanitized » environment).

The hormesis principle is also found in allergy desensitization or vaccination treatments. Subjects are exposed to a very small amount of the pathogen so that their bodies learn to resist it. Kind of like King Mithridate who, fearing being poisoned, drank a small amount of poison every morning.

It has been shown that the hormesis triggered by exposure to heat (e.g. a sauna) can improve general immunity. The one triggered by brief exposure to cold may make the immune system better able to respond to infections and bacterial toxins.

Some drugs have a protective action against infectious diseases by increasing  resistance to infection. Infectious damage to body tissue is then reduced, without the substance having any direct action on the microbe.

So-called « adaptogenic » remedies (such as ginseng) would act in this way, requiring the body to make an effort to adapt to the product, which will be followed by a strengthening of immunity and a general improvement in the ability to adapt to stress.

Production of muscle fibers

Intense effort, even of short duration, will stimulate muscle production. This muscular synthesis, which atrophies with age and its hormonal modifications, will be reinforced by hormesis.

Blood and lymphatic circulation

Hormesis can counter the progressive decrease in circulating blood volume which is linked to aging and a source of disease and degeneration. If we most often speak of brief and repeated physical or intellectual efforts as triggers, the intake of certain nutritional substances (especially vegetable and called « hormetins »), induce digestive stress that can also initiate hormesis by requiring a special effort to our digestive tract simply because they are difficult to digest.

Hormesis and cognitive abilities

Phenomena related to hormesis fight against neurodegeneration of aged patients. Under certain conditions, smoking could have a protective effect against neurodegeneration such as Parkinson’s or Alzheimer’s diseases. Of course, this example is extreme and the negative effects of more than a tiny amount of tobacco smoking far outweigh the positive effects.

The production of reactive oxygen substances during oxidation reactions can also trigger a beneficial hormesis. We know that oxidation is linked to aging, but we should, a priori, make the difference between punctual and what is called « oxidative stress ». In the latter case, the body defends itself with its anti-oxidants.

ROS (Reactive oxygen species) induced hormesis is the result of several metabolic factors including the stimulation of autophagy (a regenerating process of our cells which is triggered in particular during fasting). In fact, there are  many  hormesis factors that stimulate autophagy: fasting, intense exercise, adaptogenic substances.

Hormesis and nutrition

Fasting is now classified as a hormesis inducer. At the cellular level, our bodies have powerful mechanisms for adapting to nutrient deprivation.

Caloric restriction or protein restriction are methods to improve healthy longevity. In a situation of nutrient deprivation, the body adapts itself by involving several metabolic pathways, including autophagy, and accordingly strengthens itself.

Stress generated by a reduced diet (without going as far as malnutrition), or by periods of fasting can improve health and longevity, at least partially, through hormetic processes.

The effects of dietary restriction, however, seem to be more important in short-lived animals and are likely to be quite limited in humans, in addition to the fact that caloric restriction is very difficult to follow.

Hormesis and breathing

On one hand, depriving our cells of their vital oxygen creates great stress for them. If, however, it does not last too long, hormesis will trigger very interesting mechanisms for health. Paradoxically, hyperventilation increases the blood oxygen level, and can also activate hormesis.

It has also been shown that momentarily reducing blood circulation (as is often done before heart surgery) can protect the heart and the brain.

Hormesis and aesthetics of the body

We all want to improve our skin quality with beauty care. Various exfoliating treatments (such as peelings) with repeated micro traumatisms, by stings and facial slaps, are proposed to cope in particular with skin slackening, but should not be applied without explicit permission.

Hormesis in practice

Practicing hormesis means getting out of your comfort zone in an optimized fashion, then recovering with a period of rest. 

For example :

  • Exposure to cold: some people will take a 3-minute ice bath, others will shower in cold water.
  • Exposure to heat through the sauna or hot tub.
  • High intensity exercise: The effort is different from one person to another, depending on their physical abilities and their current fitness. It is the same idea for aerobic exercise and yoga.
  • Diet: Some people will skip a meal (intermittent fasting), others will not eat for several days. For others, alcoholic beverages in small doses have a positive effect.

Conclusion and Outlook

The proverb « What  doesn’t kill you, strengthens you » contains a grain of truth if applied wisely, but is false and even cruel if the right doses are not respected. 

For example, the descendents of people who survived the famine of the last winter of World War II in the Netherlands had poorer health. Too much adversity is harmful, exemplified today by people who have suffered severe COVID, who will almost certainly have a shorter life expectancy.

Your grandmother may have already told you: Not too much, not too little. But the dosage, the « fine tuning » of substances and actions useful for longevity requires considerable research.

It is very important to determine optimized hormetic dosages of  toxic substances prior to administering them, because there are considerable financial, political and ideological interests at stake.

The precautionary principle should join the « proactive » principle. It is not just a question of preventing what could be dangerous, but of determining what could be useful and exactly how. This is made possible by massive health data (big data), rigorous new experiments with informed volunteers, and the scientific and medical study of physical, physiological, genetic mechanisms, etc. We thus progress towards a longer healthy life.


This month’s good news: Financial support for citizen research and books related to the fight against aging


The « Unlock Longevity » donation campaign organized by the SENS Foundation has raised more than $2 million in private donations to support the most promising research!

Two books defend the advances for rejuvenation. In the English-speaking world, the book Ageless: The New Science of Getting Older Without Getting Old by Dr. Andrew Steele was reviewed in The Guardian. In French-speaking world, the book La mort de la mort. Les avancées scientifiques vers l’immortalité by José Cordeiro and David Wood, was widely discussed in the French-speaking press.


To know more about it :

February 11, 2021. Conference and workshops. Clarifying whether and to what degree the current anti-aging approaches work in mice or people.

On the occasion of the next online conference to be held on Thursday, February 11, 2021, from 17:00 to 22:00 PM CET (8.00 AM to 1 PM PDT, 11.00 AM to 4 PM EDT),

we will invite renowned scientists to give an overview of effective anti-aging studies performed on mice or rats as well as the most recent tests performed on humans.

We share with you the link of the videos cut out for each speaker as well as a synthesis of the comments and proposals made during the workshops.


Thursday, 11 February

17:00 – 17:15  Introduction Didier Coeurnelle, Ilia Stambler, Sven Bulterijs 

1. Test on mice/ rats: good practices 

17:15 – 17:30  Conboy Irina “Resetting Aged Blood to Restore Youth”

17:30 – 17:45 Vera Gorbunova  “ Promoting longevity by improving genome stability “ 

17:45 – 18:00  Rodolfo Goya  “ Rejuvenation and life extension” 

18:00 – 18:15   Josh Mitteldorf  « interactions among interventions, and why we can’t just test them separately ».

18:15 – 18:30  Harold Katcher “Breakthrough in age reversal with young blood plasma”  

18:30 – 18:40 Pause

2. Test on human: good practices

18:40 – 18:55   Nir Barzilai “TAME (Targeting Aging with Metformin)”  

18:55 – 19:10  Greg Fahy “Reversal of epigenetic aging and immunosenescence trends in humans”

19:10 – 19:25 Hanadie Yousef (Juvena Therapeutics)  « Harnessing the regenerative secretome of human embryonic stem cells to rejuvenate aged tissues » 

19:25 – 19:40  Liz Parrish “Gene therapy to reduce the effects of aging”

19:40 – 19:55 Justin Rebo (BioAge)  “Reversing immune aging to treat COVID-19 and other diseases: from discovery to the clinic”

19:55 – 20:00 Martin Lipovšek “Slovenian Levine clock project”

20:00 – 20:10 Edouard Debonneuil « Of mice and men: from the Major Mouse Testing Program to the Major Human Testing Program »

20:10 – 20:20 Pause

3. From rats to humans and the other way around? Legal, scientific, technical, and political aspects concerning Clinical tests 

20:20 – 20:35 The science, aging clocks and clinical applications.  Alexander Zhavoronkov

20:35 – 20:50 . How to  accelerate. Legal, scientific, technical and political aspects Didier Coeurnelle

20:50 – 21:05. Have the anti-aging interventions worked? Some lessons from the history of anti-aging experiments on animals and humans. Ilia Stambler 

21:05 – 21:15 Pause

4. Discussion about the 3 themes in 3 groups. Goal: one page of thoughts and proposals for each group

21:15 – 22:00 Divided in 3 zoom spaces

Rats Chair Mike Conboy and Marion
Human tests Chair Aubrey de Grey
Political aspects Alexander and Didier

5. Conclusion and goodbye


The next day, Friday, February 12 (8 – 9.30 PM CET)
Finalization of the 3 texts of thoughts and proposals (discussion online)

Same Zoom link.

Monthly letter of Heales The death of death Cosmetics and longevity N° 141 Décember 2020

Human beings are 50% composed of microorganisms that help them to function. This discovery will allow us, in the years to come, to better understand how the skin protects us, evolves and ages.

 Véronique Delvigne, Lancôme.


Theme of the month: Cosmetics and longevity


The history of cosmetics

It is above all the story of how we look at ourselves and how we look at others.  From prehistoric times to the present day, this gaze has changed, dictating fashions and enacting rules that in turn seem obsolete or, on the contrary, the height of modernity. 

It all began about 12,000 years ago when the ancient Egyptians discovered the healing powers of scented oils. From then on, their cosmetic industry developed to the point where it became an important part of their religion. The gods were honored by the general population with a wide use of cosmetics. Almost everyone used oils, eyeliners and similar products to improve appearance. Even though some of their ingredients were toxic, the appeal of cosmetics did not diminish.

Cosmetics have also found their way out of Egypt. They achieved great popularity in Greece and Rome. In the « Eternal City » there was even a time when women were not considered beautiful if they did not wear cosmetics. This led to price inflation. Rich women invested fortunes in expensive cosmetics from India and the Middle East. However, at some point, many began to regard them as extravagant and unnecessary. To combat the cosmetics epidemic, the Roman Senate enacted the « LexOppia » law of 189 B.C. which banned public displays of extravagant cosmetics and women’s clothing in all cities of the Roman Republic.


The Dark Ages in Europe were the time when cosmetics almost disappeared from public practice. Due to  the tradition of prostitutes using excessive amounts of cosmetics to hide their age and exaggerate their beauty, cosmetics were totally abandoned by the majority of the European population for centuries. Kings and Queens made public statements that wearing cosmetics was not decent, Church leaders spread the belief that cosmetics were used only by pagans and Satan worshippers, and for a very long time only actors were allowed to use them, but only during their performances.

Cosmetics in search of science

Cosmetics and care products occupy an important place in our daily lives. For example, every day, the Belgian consumer uses almost 18 grams of care products. 

In the past, noble dermatology ignored trivial cosmetics. But today, cosmetics are becoming medicalized, while dermatology benefits from the innovations of the beauty industry. Witness to this rapprochement: the rise of the term cosmeceutical promoted by manufacturers as a medical endorsement for their products.

The shift from cosmetics to research began in the early 1980s, when biologists broke into a field that had previously been in the hands of chemists and pharmacists, taking a different look at the skin: no longer a simple barrier separating the body from the outside world, but a true organ with complex immunological, sensory and physiological properties.

A series of innovations punctuated this shift toward research: the introduction in 1984 of vitamin A acid, now the favorite molecule for anti-aging products, the first skin cultures in 1985 and, the following year, Dior’s launch of liposomes, the lipid vesicles that transport the active ingredient to the area to be treated. This cascade of innovations was accompanied by a surge in research and development spending. L’Oréal, the world leader in cosmetics, has tripled its research budget in ten years to reach 985 million euros in 2019. On average, the cosmetics sector spends 4% of its revenues on research and development. However, this remains negligible compared to advertising spending.

Update on the latest anti-aging advances…

Biological decoding


Each year brings its share of innovations in terms of skin aging. But researchers are currently making such discoveries that anti-aging cosmetics could be completely overturned: « On the one hand, we have the sequencing of DNA, of all our cells and our microbiome, which gives us crucial new information about how the skin works. And on the other hand, bioinformatics, which today enables us to compile (via supercomputers) billions of biological data from studies carried out all over the world, » summarizes Véronique Delvigne, Director of Scientific Communications at Lancôme.

Microbiome 2.0


Evolving knowledge about the microbiome gives us a totally different reading of how we function and how the skin in particular functions. We know today that we are 50% composed of microorganisms (bacteria, yeasts, viruses) and that this microbiota protects us from aggression, synthesizes antioxidants, strengthens our immune system and helps healing. It also communicates with all the cells of our body, and therefore of our skin, to dictate their conduct. At L’Oréal, 9 research centers and 50 researchers are already working on the subject.

Microscopic control

The microbiota is said to  effectively be able to control our internal imbalances, areas of inflammation, skin breaches or free radical attacks. The idea is to learn how to control the microorganisms so that they can repair damaged or irritated areas. The Seed company claims that its probiotics would be « trained » to graft themselves onto the intestines and act on the inflamed areas instead of crossing them unnecessarily.

Aging Prediction Kit

In the United States, the widespread use of DNA decoding kits now makes it possible to treat dermatological aging as a classic health problem. The state of the skin is deciphered not only from its genetic capital, but also from the state of its microbiota of the moment, its morale and its lifestyle. The results give a 360° vision of each person, compressed in the form of a data bank. Passed through the filters of artificial intelligence, this information makes it possible to predict risk areas, inflammation levels or the effectiveness of different families of probiotics. At home, some kits already allow us to discover our predispositions to certain allergies, diseases or the way we are going to age. The Lifenome tests, for example, are supposed to predict a natural aptitude for running or a tendency to skin ptosis with, at the end of the day, ultra-targeted recommendations for fitness, nutrition or skin care. EverlyWell kits focus on food allergies, DHA levels and body metabolism.

Anti-aging cream based on senolytics

Senescent cells interfere with tissue function and health when they linger and multiply, as they do with age. They contribute to the chronic inflammation associated with senescence. In the skin, senescent cells are most likely responsible for a significant fraction of skin aging, which is perceived to be more problematic from the age of 50 onwards.

 Therefore, OneSkin offers a senolytic treatment. And this is happening years before the FDA approves one of the programs aimed at destroying senescent cells throughout the body.

Collagen, the protein that keeps you young

Collagen is a protein that gives resistance and elasticity to skin, bones, muscles, cartilage and ligaments.

It is today the object of intense marketing: beauty creams, drinks, powders, food supplements. Of course! Everyone would like to be filled with collagen again like children with their soft cheeks, peachy skin and supple joints.

Unfortunately, our collagen production decreases with age. In addition, collagen proteins present in our body are degraded by sunlight, pollution, free radicals and junk food.

Collagen, in particular, is vulnerable to excess sugar. It is also damaged a lot by AGEs (Advanced glycation end-products). AGEs are toxic molecules contained in the « crispy bit » of meats and fried foods, which we consume too much of.

Because of the non-renewal of collagen, older people experience a kind of general decay of the body. This is problematic at all levels: osteoporosis, osteoarthritis, aging of tissues (wrinkles).

One of the best known (and most sought-after) functions of collagen concerns wrinkles. A study published in 2014 on women between 35 and 55 years old showed an increase in skin elasticity in 4 weeks, under the effect of a supplement of collagen hydrolysate.

The « aging well », an evolution of anti-aging before going further?

Anti-aging is the fundamental trend in the sector, which can be found in all brands in the form of day/night creams, serums, masks, sprays, make-up, etc. Consumers love skin care products that reduce wrinkles, even out and brighten their complexion, reduce pigmentation spots, in short: to limit or even repair the signs of aging.

However, cosmetic products are still dedicated to daily surface use that can improve the appearance of the skin for a limited time. They are not drugs or invasive surgical procedures that completely reverse the effects of age. Anti-aging claims on trademarks are increasingly controlled with countries, such as the United States, Canada and European countries, regulating the appearance of such claims on packaging and limiting the scope of the terms used.

The current trend is towards self-acceptance, respect for one’s body and accompanying it in its daily well-being. In this context, articles are multiplying on the notion of « aging well », which adds a nuance to the classic « anti-aging ».

For thousands of years, women and men have sought to stave off the irreparable outrage of the passing years, for their physical appearance as well as for their health. Cosmetics have only a limited role in this regard. To go further, only knowledge, particularly in terms of genetics, massive data analysis, and understanding of all the organisms that make up our bodies, can contribute to the radical advances needed for a much longer healthy lifespan.


The good news of the month :


Massive data in the field of health is increasingly interconnected. This is a positive step forward in the fight against age-related diseases. It is a matter of better understanding in order to fight better, for example against Covid 19, this disease that unfortunately continues its deadly growth in recent weeks.

Overall positive developments are particularly noticeable:

In France, the Health Data Hub enables the pooling of a large amount of health data. Some concrete projects are progressing. But more public confidence is needed. Emmanuel Bacry, the Hub’s Chief Scientific Officer, said on December 9, 2020: << I think it’s extremely important to explain to citizens what it means to share data, to really explain to them what the real risk of data sharing would be, but also its benefits, and what we can expect from it. (…) There can be positive fantasies. Thanks to artificial intelligence, I’m going to live to be 200 years old. There are negative fantasies. My data will be taken by insurance companies and I will be evaluated and graded. »

In Finland, for several months now, all health data has been linked via a public body called FinData. It is worth noting the broad consensus that exists when the guarantees of public authority, scientific interest and lack of commercial interest are integrated into the project. The system provides that citizens who wish to take part may « opt out ». But as of November 10, 2020, less than 200 people out of about 6 million Finnish citizens have wished to have their data not accessible – according to Johanna Seppänen, director of the institution.

At the European level, progress on the « European Data Space » is fast. A text relating to new rules for data sharing within the Union is being drawn up, with a text on health projected for early 2021. Perhaps the most positive step forward is more in terms of ideas than in technical terms. The European Union is proposing a new concept, that of an « altruistic database » managed by non-profit organizations.

In the United States, the « All of Us » project aims to pool the extensive health data of a million volunteers. Results linked to the biological samples of 270,000 people already actively involved have recently become available to researchers and volunteers themselves.


Find out more:

Studies financed by Heales: Effect of young rat plasma on the lifespan of aging rats. 21 december 2020.

Studies financed by Heales: 

Effect of young rat plasma on the lifespan of aging rats

Heales supports two experiments on the rejuvenation of elderly rats through transfusions. The maximum longevity thanks to these treatments will be measured for the first time. Whether the results are positive or not, they will be published. To accelerate this research or to close doors.

Today, in spite of the gigantic progress in medicine and research, we still do not know how to be healthy beyond about 85 years of age. 

The use of blood plasma to address the issue of human longevity is still controversial, and companies like Alkahest and Ambrosia are never far from the headlines. 

Mice and rats also experience old age, but much earlier than we do, starting at about 2 years.  And they never get older than 4 years old… 

A recent study that has not been peer-reviewed, signed notably by Harold Katcher and Steve Horvath, details a procedure of reverse aging using Elixir that is wholly derived from plasma. Young rat plasma was administered to 2-year-old rats and their physiological indicators during the test had almost become those of 6-month-old rats. 

The results, obtained using Horvath epigenetic clocks, showed a mean age inversion of 54.2% in four tissues. Specifically, liver tissue rejuvenation was measured at 75%, blood rejuvenation at 66%, heart rejuvenation at 57% and hypothalamus rejuvenation at 19%. 

However, this study does not test longevity per se. This is why the Heales organization decided to fund, with a rather modest but useful amount (2 times 25,000 dollars), two studies on the maximum longevity of these animals. One will be conducted by Professor Harold Katcher in his laboratory in India and the other is under the direction of Professor Rodolfo Goya at the Institute for Biochemical Research in Argentina. 

Based on the above information, we decided to evaluate the possible effect of the plasma of young rats on the lifespan of older rats (25 months). Specifically, we propose to compare the survival of older rats treated intravenously with young plasma with that of corresponding age controls (untreated). We also propose to collect blood samples from all animals, every other week, in order to follow the evolution of epigenetic age over time. As a functional assessment, we plan to evaluate the performance of spatial memory before the start of treatment and 3 months after. Cognitive tests will include an evaluation of motor performance.

Already 15 years ago, this surprising lead in the quest for rejuvenation was opened with the experiments conducted by Irina and Michael Conboy and their colleagues at Stanford University. 

To verify this, their team had temporarily connected the vascular network of young mice to that of older mice, as if they were Siamese twins, a complex surgical operation called parabiosis. And they found that the muscles and liver of the older mice regenerated more efficiently, while the opposite occurred in the younger mice.

A new study, led by Irina and Michael Conboy of Berkeley University, has revealed an interesting new avenue in efforts to combat the effects of aging. The team’s research showed how diluting the blood plasma of older mice can have a strong rejuvenating effect on tissues and organs by reducing the concentration of inflammatory proteins that increase with age.

Half of the mice’s plasma was exchanged for a solution composed of salt water and albumin. This significantly improved the health of the aged mice. The rejuvenation effects on the brain, liver and muscles were the same or greater than in the first experiments in 2005! 

We also hope that Irina and Michaël Conboy, brilliant researchers in this field, will agree to test the longevity of the mice with their plasma dilution technique.

Attention, Please note that the financing of these studies does not mean that Heales vzw is certain of positive results. On the contrary, a major effect unfortunately seems rather unlikely. But, apart from the fact that we would love to be wrong to be pessimistic, in the most probable case these studies on the longevity of rats aim to « close doors », to determine which avenues of research should be continued and which have a limited (or even negative) impact. 

To learn more about the protocol used in these two studies, here are the corresponding documents: 

Rodolfo Goya
Harold Katcher

The Death of Death N° 140 Clinical Testing and Longevity. November 2020.

It would be more useful to find out how to make our genome permanently worry-free rather than looking for palliative solutions.

Some ethics specialists believe that they are alone on what they believe to be the right path to progress! They want the slow road that will leave billions of deaths behind because of the lack of preventive/curative care that genome modifications would have allowed.

This vision exasperates me because patients need concrete solutions, not moral bullshit.

Arnaud D. Longevity activist, private email in November 2020.


Theme of the month: Clinical Testing and Longevity


 

Clinical Trials 

Clinical trials are an essential phase in the development of new drugs. Halfway between research in the laboratory, on cultured cells or animals (rodents, monkeys…), and patient care, this long process takes place in several phases and ensures that the benefits outweigh any risks. It is an indispensable element in the elaboration of big data for health and longevity.

In particular, clinical trials make it possible to determine the populations for whom the drug is most effective and the optimal conditions of use (route of administration, concentration, dosage, etc.). There are three phases in these clinical trials, necessary before the molecule can be authorized for sale as a drug; plus a fourth phase after the product is marketed.

Phase 1, evaluation of the toxicity of the molecule

A Phase 1 clinical trial is the very first use of a new molecule in humans. It may be remunerated. The molecule is tested over a short period of time, from a few days to a few months and on a small number of people, no more than a few dozen.

The objective of the phase 1 trial is to carry out a short-term assessment of the safety of the product’s use, i.e. its possible toxicity, its short-term evolution in the body and an initial pharmacokinetic profile.

In France, the National Agency for the Safety of Medicines (ANSM) states that in this type of first administration trial, « the first dose of the new active substance administered must not cause any detectable short-term toxic effects ». According to Leem (French association of drug companies), 30% of products tested fail to pass this first phase.

Phase 2, efficacy and optimal dosage studied

Once toxicity has been studied, it is the efficacy of the product that is evaluated in phase 2 trials. This type of trial is carried out on small homogeneous groups of 10 to 40 patients with the targeted disease, over a period ranging from a few months to 2 years. The aim is to determine the most appropriate dosage, the smallest effective dose for a given pathology, and to optimize the pharmaceutical form of the product. Only one third of products tested would pass Phase 1 and 2 trials.

Phase 3, the study of the benefit/risk ratio of the drug candidate

This time, the drug candidate is tested on a large sample of patients (at least several hundred), often in international studies.  This involves comparing the drug in development to a placebo (a drug with no therapeutic effect) or to another proven drug. Ideally, this phase should be carried out with randomly selected groups. The objective is to prove efficacy and to evaluate the efficacy/tolerance and benefit/risk ratios of the molecule. This step should also allow the demonstration of possible interactions with any other simultaneous medication.

It is only after these validation steps for the molecule that the drug can eventually obtain marketing authorization (MA). Between 70% and 90% of drugs entering phase 3 are retained for a marketing authorization application.

Phase 4, long-term post-marketing follow-up

This additional step is a follow-up phase of the drug now on the market. Trials are carried out throughout the marketing of the drug and allow to deepen the knowledge of the product in real conditions of use and to detect rarer adverse effects that cannot be detected beforehand.

European regulations

The European regulation EU 536/2014 on Clinical Trials (CTR), which came into force in 2019, brings about a major change for European researchers. The main objectives of this important change in legislation are administrative simplification and harmonization at the European level.

Via a central EU portal, only one application (CTA, clinical trial authorization) will have to be submitted per clinical trial by the sponsor from all Member States taking part in the clinical trial. Only one of the Member States will be designated by the sponsor as « Rapporteur Member State » which evaluates the application centrally and then issues a single opinion to the sponsor and the other Member States concerned.

Situation in the United States

The Food and Drugs Administration (FDA), an agency of the U.S. Department of Health and Human Services, protects public health by ensuring the safety, efficacy and security of human and veterinary drugs, vaccines and other biological products for human use, as well as medical devices.

Over the past several decades, the FDA has encouraged registration practices that would lead to clinical trials that better reflect the population most likely to use the drug if it is approved, primarily by broadening the eligibility criteria. Despite these efforts, difficulties in participating in clinical trials remain, and certain groups continue to be under-represented in many clinical trials, particularly older people.

It should be noted that the U.S. National Library of Medicine’s Clinical Trials site is the official reference for reported clinical trials occurring anywhere in the world.

Ethics Committees

The notion of protection of persons in research practices appeared in the 1930s. After the Second World War, following the atrocious experiments carried out by Nazi doctors and Japanese war criminals, international awareness of the ethics of human experimentation for the protection of individuals began to emerge.

In 1947, the Nuremberg International Tribunal defined a code made up of ten rules, universally known as the « Nuremberg Code« . This Code « recognizes » that experimentation on humans « for the good of society » is permissible and stipulates that « the voluntary consent of the human subject is absolutely essential ». This was followed in 1949 by the International Code of Medical Ethics and in 1964 by the Declaration of Helsinki.

Most countries where clinical research is conducted currently have their own ethics committees, as do the countries of the European Community and the United States. Unfortunately, ethical approvals are often slow and still differ even within the European Union depending on the country (and sometimes even regionally). As a consequence, even in the time of Covid, some research is still considerably slowed down.

Eroom’s law

Eroom’s « law » is the observation that drug discovery becomes slower and more expensive over time, despite technological improvements, a trend first observed in the 1980s.

The cost of developing a new drug roughly doubles every nine years (adjusted for inflation). The current cost of developing a drug based on a new substance is estimated at one billion dollars! To contrast this with the exponential progress of other forms of technology over time, this conjecture has been deliberately called Moore’s Law in reverse.

Self experiments

The famous geneticist George Church didn’t want to wait for the results of the clinical trials. In what appears to be the first « citizen science » vaccine initiative, Preston Estep and at least 20 other researchers, technologists and science enthusiasts, many of whom are linked to Harvard University and MIT, have volunteered as « lab rats ».

To develop a vaccine, the group, called the Rapid Deployment Vaccine Collaborative, or Radvac, studied reports of vaccines against SARS and MERS, two other diseases caused by coronaviruses. The goal is to find « a simple formula that you could make with readily available materials, » says Estep. The vaccine, administered nasally, could create what is called mucosal immunity, that is to say immune cells found in airway tissues. This local immunity could be an important defence against SARS-CoV-2. But unlike antibodies that appear in the blood, where they are easily detected, signs of mucosal immunity may require a biopsy to be identified.

Clinical trials. How to advance medicine. Consent, a condition that is sometimes somewhat fictitious.

Without clinical trials: no new therapeutic methods, no new drugs. Every year, thousands of citizens engage in clinical trials to test new drugs.

Clinical trials must be conducted under the direction and supervision of a physician who must clearly inform the volunteer and obtain « informed » consent about the purpose of the research, its methodology, expected benefits, foreseeable constraints and risks, and the right to refuse to participate in research. Anyone who has consented to participate in research is free to withdraw consent at any time, and thus stop participating in the research.

The law makes it clear that the interests of those who participate in clinical research always outweigh the interests of science and society. In this area, we have moved from one extreme to the other, from abuses of human experimentation to provisions where even those who accept to take informed risks for the common good are not allowed to do so. Moreover, this extremely cumbersome legislation does not harm certain private interests, on the contrary. Only the big pharmaceutical companies are able to carry out the tests and to remunerate expensive and time-consuming legal and administrative staff. Small competitors are therefore eliminated (or absorbed), regardless of the value of their ideas.

Finally, it should be noted that for seriously ill people in hospital who are offered an experimental treatment, no matter what happens, informed consent is best summed up as « We are offering you a treatment for which we think you have a better chance of survival (or improvement). You are free to take that chance or increase your risk of dying ». Since the patient will still remain in the same facility if he or she refuses, even if the doctor is acting in perfect good faith, this limits the « free » character.

A question of patents and financial interests (Belgian example)

In 2018, 162 patent applications for drugs and/or vaccines were filed in Belgium (+30% compared to 2017), 507 new clinical studies were initiated and 1,399 drug studies were conducted. Last year, nearly 3.6 billion euros were invested in research in Belgium by (bio)pharmaceutical companies.

Three out of four clinical trials (77%) are organized and financed by the (bio)pharmaceutical companies themselves. The remaining 23% are carried out at the initiative of the academic or public sector. This proportion of private funding is one of the highest in Europe. Direct public investment in health is low. There is a high level of tax and other support for the privatization of research.

And the consequences for longevity research?

Measuring the impact of therapies for the elderly is complex. Obtaining their « informed » consent is often impossible, especially in the fight against neurodegenerative diseases.

Conducting clinical tests to fight against aging will be difficult, especially because deaths or accidents during clinical tests inspire fears. However, by definition, with or without treatment, mortality and morbidity will be higher in older subjects.

Yet, as we have seen with Covid research, enabling the oldest and most fragile people to live longer can become an almost absolute priority, even at considerable economic cost. Confidence is generally greater when research is carried out by non-profit organizations (public or not), leading to research results that can benefit everyone, without commercial involvement.

There are millions of young, old, and very old men and women who are willing to give informed consent (or who were willing to do so when they were still fully aware) for healthy longevity advances, even if they are not certain to benefit directly. In any case, in the event of experimental treatment, these people will benefit from very detailed follow-up, which will almost always be favorable to their health.


The good news of the month : Progress on Covid-19


In several countries, including France and even more so Belgium, overall mortality in 2020 will unfortunately be higher than in 2019.

Fortunately, at the end of this year, the huge efforts in vaccine research are now making it possible for products to be used no longer in the test phase, but on the general population, with a strong predicted efficacy and few side effects. Of the more than 300 vaccines in development worldwide, three are already being administered to the general population (two in China and one in Russia) and three are approaching this stage for the rest of the world (vaccines from consortia including Pfizer, AstraZeneca and Moderna, respectively).

No doubt, complex discussions will be held about choices, prices or anti-vaccine opposition. To get to where we are today may seem like a long road. However, the epidemic is less than a year old. Never before has a vaccine against a virus of the coronavirus family been made. The development of a new vaccine normally takes years.

A more « incremental » piece of positive news is that thanks to better knowledge of the disease and of therapies, especially in intensive care, mortality has decreased quite slowly but steadily for patients with the disease.


Find out more:

The Death of Death. The most well-known longevitists. No. 139 October 2020

I, personally, if there are technologies that can extend my life, and I have access to them, yes, I would choose to use them. But I also think that there are going to be individual questions because in the name of this freedom, we are also going to create inequalities between human beings. (…) There is going to be a radical moment (by) the conjunction between gene therapy and nanotechnology (…) which means that we are going to have treatments that are not only extremely effective in treating diseases related to aging, but also perhaps even in halting aging.

Corinne Narassiguin, French politician, number 2 of the Socialist Party, talking notably about possible ways of making these therapies accessible one day to all those who wish to have them. 


Theme of the month: The most well-known longevitists


Obviously, the choice below is subjective. It is an overview of some of the women and men committed to making a much longer and healthier life possible. They have expressed themselves behind their test tubes, in their academic research, but also in front of cameras. The diversity of their approaches illustrates the difficulty and richness of the work in this field that concerns us all.

Aubrey De Grey 

Aubrey de Grey is an English scientist, former computer scientist at the University of Cambridge and was initially self-taught in bio-gerontology. He now lives in California.

Inspired by Dr Denham Harman’s 1972 « Mitochondrial Theory of Aging », he developed a project called SENS (Strategies for Engineered Negligible Senescence) to prevent age-related physical and mental decline.

He proposes to develop a means of regenerating cell tissue that will rejuvenate and extend human life expectancy without any time limit. He says he has identified seven causes of the aging process that must be countered in order to successfully complete this project.

Regarding his past career as a computer scientist (and then as a bioinformatician in genetics), Aubrey de Grey says :

There are really important differences between the creativity of a scientist and that of a technical engineer. It means that I am able to think in many very different ways, and end up with approaches to things that are different from the way a normal scientist thinks

In 2007, he wrote a book, Ending Aging, with Michael Rae, which summarizes the scientific, political and social issues of the SENS project. He is the editor of the journal Rejuvenation Research. He is also a polymath, occasionally able to solve a mathematical problem that has remained unsolved for decades.

Irina Conboy

Irina Conboy is a Professor at the University of California, Berkeley, in the Department of Bioengineering. Her discovery of the rejuvenating effects of young blood through parabiosis in a seminal article published in Nature in 2005 paved the way for a thriving field in the biology of rejuvenation. Her husband, Michael Conboy, works with her.

A study published in May in the journal Aging shows that similar age-reversal effects can be achieved by simply diluting the blood plasma of old mice without using young blood.

In humans, the composition of blood plasma can be altered by a clinical procedure called therapeutic plasma exchange, or plasmapheresis, which is currently approved by the U.S. Food and Drug Administration for the treatment of various autoimmune diseases.

David Sinclair 

David Sinclair is an Australian biologist who is Professor of Genetics and Co-Director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School.

He is known for his research on aging, including being appointed an Officer of the Order of Australia (AO) for « distinguished service to medical research on the biology of aging and life extension, as a geneticist and academic, to biosafety initiatives and as an advocate for the study of science ».

Dr. Sinclair is co-founder of several biotechnology companies (Sirtris, Ovascience, Genocea, Cohbar, MetroBiotech, ArcBio, Liberty Biosecurity) and serves on the board of directors of several others. He is also co-founder and co-editor of the journal Aging.

In particular, he is working on substances called sirtuins, a class of enzymes that act as « circulating agents », mobilizing a large number of proteins to repair and defend cells.

Miroslav Radman

Miroslav Radman likes paradoxes. In the same sentence, this rigorous scientist, passionate about art and singer in a choir, explains having created, in Split, in a former Croatian military barracks, the Mediterranean Institute of Life Sciences (MedILS), which operates with a « college » spirit but like a jazz band!

A former researcher at Harvard, but also in Zagreb and Brussels, he has been awarded numerous scientific prizes, including the French Inserm Grand Prix. He is Professor of Cell Biology at the University Paris Descartes, and a member of the National Academy of Sciences. He is also the author of the book Le Code de l’immortalité. 

This famous biologist-geneticist seeks to revolutionize studies on aging. After working on DNA and genes, but also on the extremophilic and hyper-resistant bacterium Deinococcus radiodurans, he deciphers our bacteria and repair proteins, paving the way to new therapies for degenerative and cancerous diseases. 

Steve Horvath 

Steve Horvath is a German-American researcher, geneticist and biostatistician specializing in aging. He is a professor at the University of California at Los Angeles, known for developing the aging clock that bears his name, which is a highly accurate molecular biomarker of aging, and for developing weighted correlation network analysis.

According to him: Once we know how to accurately measure aging, we can study it and overcome it.

He works on all aspects of biomarker development, in particular genomic biomarkers of aging. He has developed a very accurate multi-tissue biomarker of aging known as the epigenetic clock.

Nir Barzilai

Dr. Nir Barzilai is founding director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York

I think prevention of aging is really good. … and I think life is going to be very different in the next decade because of our progress.

On his agenda for several years has been the development of a clinical trial, unique in the world, which aims to show that one molecule can delay the onset of all the diseases whose incidence increases with age. Its name: metformin, a well-known drug that reduces insulin resistance in the treatment of type 2 diabetes.

The TAME (Targeting Aging with METformin) study is funded by a non-profit association, AFAR (American Federation for Aging Research). « No one will make money if this drug proves to be effective because metformin is a generic that costs only a few cents per dose”, he says.

Cynthia Kenyon 

Cynthia Kenyon is an American molecular biologist who studies the genetics of the aging process (gerontogenesis).

Dr Kenyon studied chemistry and biochemistry and received her PhD in 1981 from the Massachusetts Institute of Technology.

In Cambridge, she studied the Hox genes, active in the morphogenesis of drosophila (fruit flies). She then directed UCSF’s Hillblom Center for the Biology of Aging in San Francisco.

In particular, she demonstrated that by acting on a single gene (named daf-2) and destroying cells of the reproductive system, the lifespan of the nematode Caenorhabditis elegans could be multiplied by 6, from less than 3 weeks to 4 months.

Dr. Kenyon is currently employed by Google Calico as Vice President and Researcher on Aging.

Brian Kennedy 

Brian Kennedy is internationally recognized for his research on the biology of aging and for his work in translating research discoveries into new ways to delay, detect and prevent human aging and related diseases. He currently works in Singapore. From 2010 to 2016, he was President and CEO of the renowned Buck Institute, where he remains a professor.

Our work on multiple animal models shows that the processes that lead to aging are conserved in the species. The study of these common pathways makes it possible to develop therapies that would slow down the aging process, thus preventing chronic diseases.

Jean-Marc Lemaître 

The biologist Jean-Marc Lemaître was born on October 14, 1963. As a child, he enjoyed observing the ponds of his native French region, Picardy, to study the transformations of newts and tadpoles. A passion that led him to study developmental biology. As a research fellow at the Institute of Functional Genomics (Inserm/CNRS/University of Montpellier), he tries to demonstrate that aging is reversible.

In November 2011 he succeeded in doing so and published his work on cell rejuvenation in the American journal Genes and Development.

This is a considerable clinical success, comments Jean-Marc Lemaître. If we are able to delay cell aging, we may then be able to delay the development of certain pathologies.

Maria Blasco 

Dr. Blasco is a molecular biologist whose main interests, since the time of her university studies, have been cancer and aging. After obtaining her PhD at the Center for Molecular Biology in Madrid, she moved to Cold Spring Harbor, New York, to work as a post-doctoral researcher in the laboratory of Dr. Carol Greider, the same Carol Greider who co-discovered telomerase with Elizabeth Blackburn in 1995.

At the time, the link between cancer, aging and telomerase was just a hypothesis that had yet to be proven, and Blasco set out to clone the mouse telomerase gene and create telomerase knockout mice to study the effects that lack of the enzyme would cause in animals.

George Church 

As bearded, gifted and often as anti-conformist as Aubrey de Grey, George Church is an American chemist, geneticist and molecular biology engineer, best known for a book Regenesis, co-authored with Ed Regis, subtitled « How Synthetic Biology Will Reinvent Nature and Ourselves », which presents a future where genetic engineering will have improved human and animal health, increased our intelligence, memory and lengthened our lives.

He took a list of 400 genes identified as potentially responsible for longevity in humans and reduced it to 45. Today, he is developing different techniques to target combinations of these genes. Our main goal is to reverse the aging process, explains Church, We know that by changing the rules, we can increase life expectancy by two and a half years in rodents and 200 years in bowhead whales.

Gene sequencing, he adds, is almost 3 million times less expensive than it was ten years ago. It allows us to use synthetic biology, and we are no longer restricted by the limitations of living things. 

Church’s work is funded in part by the Wyss Institute. The scientist has also received funding from Google and Peter Thiel. 

Laura Deming

Laura Deming is a biologist and founder of The Longevity Fund, the first venture capital firm to focus on companies working to extend the lives of healthy human beings and combat age-related diseases through biotechnology.

This is how she describes the birth of her commitment:

I remember one time when my grandmother came to visit us. I had never been with anyone over 60 before. (…) For my grandmother, just getting up from a chair was really painful. (…) I remember asking my parents what the disease was. They told me: she doesn’t have an illness, she is old. I asked them what disease it was to be old. They said, « Oh, no, no, you don’t understand, it’s a natural process. And as a child, you say to yourself: « This is stupid. Why is there a natural process that we should all get, a disease that makes us so damaged? »

Alex Zhavoronkov 

Alex Zhavoronkov is the founder and CEO of Deep Longevity, Inc., a global company that develops a wide range of biomarkers of aging and longevity based on artificial intelligence. He is also the founder and CEO of Insilico Medicine, a leader in artificial intelligence technologies for drug discovery and biomarker development.

Since 2015, he has invented critical technologies in the field of « Generating Adversary Networks » (GANs) and Reinforced Learning (RL) for the generation of new molecular structures with desired properties, and the generation of synthetic biological and patient data. He has also pioneered applications of deep learning technologies for predicting human biological age using multiple types of data, transferring learning from aging to disease, target identification, and signaling pathway modeling.

A certainly incomplete list, and some favorites 

To make a choice involves abandoning other options. We could have written about many other researchers as well. There are thousands of them who struggle day after day to repair what dramatist Jean Racine called the irreparable outrage of the years. The brilliant Greg Fahy and his thymus studies, Josh Mitteldorf and his Data-Beta Project studying the cumulative effects of longevity therapies, Michael Rose, who worked on the notion of antagonistic pleanthropy, William Andrews, the telomere specialist who also runs ultra-marathons, BioViva‘s controversial Liz Parrish who has experimented with gene therapies on herself, the specialists of (super)centenarians including Jean-Marie Robine and Leonid and Natalia Gavrilov.

They are many others less well known: the hundreds of collaborators of the above-mentioned scientists, Sven Bulterijs, co-president of Heales, who each month produces a review of longevity news, Ilia Stambler, the best historian of the sciences of longevity, author of the monumental Longevity A History of Life-Extensionism in the Twentieth Century, Kevin Perrott and his organization Open Cures, Alexandra Stolzing, who strives to rejuvenate mice with conviction and discretion, Guilhem Velve Casquillas, creator of the LongLongLife site and of multiple companies, the Russian Maria Konovalenko, photogenic scientist and activist working, like many others, in Silicon Valley, Laurent Simons, the gifted Belgian child who is 9 years old wanted to make his grandparents live forever…


This month’s good news: Eurosymposium on Healthy Ageing 2020


The 5th edition of the Eurosymposium took place online on October 1st, 2020 on the occasion of the International Day of Older Persons. 

This event brought together leading scientists to address the topic of biomarkers of longevity as well as clinical testing.

Videos, separated for each speaker, are available on Youtube.

Following this conference, a declaration was adopted to facilitate biomarker research and clinical testing. Here is an excerpt from it:

There should be an obligation for ethical committees to decide within a reasonable time on the diagnostic tests on biomarkers of aging and clinical research of geroprotective therapies (not more than one month, unless providing a justification for the delay). Deciding faster must not mean being less careful, on the contrary (…)

By enhancing the evaluation of clinical aging biomarkers and testing new geroprotective therapies, it may be possible to radically reduce degenerative aging processes, and thus increase the health and economic benefits of the rapidly aging society.  We must mitigate senescence processes as soon as possible to save as many lives as possible.


To learn more:

How to Significantly Extend Healthy Lifespan Declaration on Biomarkers and Clinical Tests

Scientists from around the world met today during the International Day of Older Persons to share their research on the extension of healthy lifespan. Two topics emerged as particularly important: biomarkers and clinical tests.

Scientific research and technological innovation have already significantly improved the life expectancy and health of the population. Many of the biological mechanisms by which we age (« hallmarks of aging ») have been identified but require further exploration as targets for intervention. There are proofs of principle that therapeutic interventions into these mechanisms can improve healthspan in animal models and in human pilot trials. More needs to be done to improve the healthy and productive life expectancy for the aging population. 

We are calling for more research and development to therapeutically treat aging as the main factor for disability and death to improve the resilience and immunity of the elderly. Staying healthy and independent for as long as possible is everyone’s wish, as well as a major public health goal as we strive to build a more resilient society. The differences observed between biological and chronological age may enable health professionals to implement targeted and personalized actions.

The goal would be to combine different biomarkers of aging to develop a generally acceptable measure of aging and degenerative processes. This is necessary in order to better understand and predict the aging process, as well as to have common metrics to evaluate the effectiveness and safety of potential geroprotective treatments. The use of the latest machine learning techniques to find even more relevant markers and predictors of aging could be an important milestone. Advances in artificial intelligence, combined with the availability of large databases, make it possible to identify and integrate many more biomarkers. These biomarkers should give reliable information about aging of all systems of the body (immune, cardiovascular, respiratory, nervous, etc.) and their integration. It is also important to have more open and collaborative databases about these biomarkers, accessible to the public while ensuring individual privacy rights.

There are emerging initiatives in this area, including databases on actionable biomarkers of aging: Mortality Predictors (http://mortalitypredictors.org/); Longevity Biomarkers (https://www.aginganalytics.com/biomarkers-of-longevity); Deep Biomarkers Of Human Aging (http://young.ai), and other relevant resources, such as Human Aging Genomics Resources (https://genomics.senescence.info/index.php) and Geroprotectors (https://geroprotectors.org/). These and analogous initiatives must be supported.  The science community needs open databases including case studies, solutions, and datasets.

Another crucial point we have identified is the need to enable the validation of research on aging and geroprotective therapies by clinical studies.

To this end, the recruitment of appropriate subjects is critical. It is especially important to recruit people aged over 60 years and even 70, 80 or 90 years for clinical studies. It is important to test the therapies in the groups for whom they can produce benefits, following the International Council on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) criteria for geriatric drug development. Clearly there are risks for older persons in such studies, but the risks and dangers of not developing therapies and/or applying untested therapies are much more detrimental. It should be absolutely necessary that there is an informed consent and a process of ethical review.

To accelerate decisions:

  • There should be an obligation for ethical committees to decide within a reasonable time on the diagnostic tests on biomarkers of aging and clinical research of geroprotective therapies (not more than one month, unless providing a justification for the delay). Deciding faster must not mean being less careful, on the contrary.
  • Authorizations should be more standardized, interoperable and transferable between countries.
  • Standards for protecting the privacy of medical data of trial participants should be established that allow easier collaboration between institutions, countries, etc. 

One way to accelerate the research could be also via self tests by scientists (e.g. the Rapid Deployment Vaccine Collaborative initiative http://radvac.org). 

By enhancing the evaluation of clinical aging biomarkers and testing new geroprotective therapies, it may be possible to radically reduce degenerative aging processes, and thus increase the health and economic benefits of the rapidly aging society.  We must mitigate senescence processes as soon as possible to save as many lives as possible.

More information:
Virginie Stephenne, scientific collaborator
Didier Coeurnelle, Co-chair, Heales.org, info@heales.org, +32 489 43 55 94.