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? 

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

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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.

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

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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.

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To know more about it :

• See in particular : heales.org, sens.org, longevityalliance.org and longecity.org.
• image source.

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.

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Theme of the month: Cosmetics and longevity

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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.

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The good news of the month :

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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.

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Find out more:

• See in particular : heales.org, sens.org, longevityalliance.org and longecity.org.
• Source of the image.

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. 

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Theme of the month: The most well-known longevitists

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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…

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

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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.

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To learn more:

• See in particular: heales.org, sens.org, longevityalliance.org and longecity.org.
• Image source: produced by the editorial staff.

I have a dream that one day humans will unite and say: We hold this truth to be self-evident that what serves the right to health is a common good.

I have a dream that one day medical data, research data for health and longevity will be accessible to all and will allow for a longer and healthier life, with more solidarity.

I have a dream that those who were sick and those who were overwhelmed by bureaucracy, regulations and financial or psychological factors will find sisters and brothers to be all together more resilient, happier and proud to help each other.

I have a dream that the hell of privatized and dispersed knowledge will be transformed into an Eden of knowledge sharing to enable a much longer healthy life for all.

Text inspired by « I have a dream » by Martin Luther King.

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Theme of the month: Sharing health data and longevity

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Our health data

Of all the personal information stored in computerized form, but also often in paper format, information relating to health and all our biological data is among the most numerous, the most sensitive and the most useful.

Since the beginning of the history of medicine, healthcare has been delivered through collective knowledge, individual experiences, often inaccurate beliefs and knowledge of the patient’s condition.

It is only relatively recently that patient data have become an important part of the field of knowledge, not only for the treatment of individuals themselves, but also for medical research.

How to share health data?

Since the end of the 20th century, the concern to protect privacy has been growing. Initially, the measures taken were aimed at, and resulted in, preventing abuses. Today, the combination of regulations and practices relating to medical data and, more broadly, all the regulations and practices concerning the privacy of citizens has resulted in :

• The citizen does not have access to their own medical data in a simple way.
  
• The citizen does not have the opportunity to participate in medical experimentation and share knowledge scientifically, even if he or she wishes to do so out of personal or collective interest and even if he or she has given explicit informed consent.
  
• Researchers do not have access to the detailed health data of most citizens.
  
• Medical data is often the subject of opaque and self-interested commercial transactions.
  
• The development of research using artificial intelligence and « massive medical data » is slowed down, as biased and sold data potentially contains more inaccuracies.

It is perfectly normal that citizens are protected from illegal uses of private data that could be harmful to them. But the protection should stop there. It is immoral, and it should be illegal, for data useful to public health to be withheld from researchers, when this does not cause harm to the people from whom the data originates.

In an ideal world, the fact that medical data may have value for research should not give rise to financial transactions except in relation to the cost of the operations required to make the data available.

The current situation does not ensure the protection of privacy, it prohibits almost totally, in fact and in law, the effective sharing of data. As far as classical medicine, medical records, relations with our health institutions, pharmaceutical information, etc. are concerned, we only have restricted and temporary access to them. The lack of sharing to prevent and reduce the impact of diseases in the future is particularly regrettable for information concerning the elderly (indicators of neurological diseases, detection of falls, …).

Some private and public organizations sharing data

New tools, such as the mass processing of health data and artificial intelligence, will enable significant progress in patient support, evaluation and choice of treatments and management of the healthcare system. This is why many players are investing in this field.

• Health Data Hub (HDH) is a health data sharing platform launched in December 2019 in France. Its objective is to promote the use and multiplication of the possibilities for exploiting health data, particularly in the areas of research, support for healthcare personnel, healthcare system management, patient monitoring and information. The HDH enables the development of new techniques, particularly those related to AI methods. It also has a role in promoting innovation in the use of health data.
• A similar project exists in Germany: the Medical Informatics Initiative (MII). The French and German projects share the same objectives but differ in terms of methodologies. The HDH project is based on a top-down approach and focuses on a shared computing infrastructure, providing tools and services to accelerate projects between data producers and users. The MII project is based on a bottom-up approach and relies on four consortia comprising teaching hospitals, universities and private partners.
• Apple places a lot of emphasis on health and wellness features with its Apple Watch. The latest model can measure heart rate, warn of falls and perform an electrocardiogram (ECG) thanks to an optical sensor. Unfortunately, both the Apple firm and firms offering similar services do not share the information.
• The X-Prize Foundation promotes the integration of healthcare data. Breaking down barriers to data access while respecting privacy and security principles is a huge challenge and a tremendous opportunity. Standardized, aggregated and granular patient data that can be shared across systems is the foundation for low-cost, high-quality healthcare, including enabling front-line healthcare systems to function optimally and efficiently. In addition, this data is essential for A.I. algorithms to deliver information.

Promote health uses, prevent illegitimate uses

Your insurer, your banker, the government knows a lot about you. Google, Facebook, your employer and your neighbor too. They don’t normally use it for illegitimate purposes.

What is needed first of all is to prohibit the illegitimate use of information and ensure effective sanctions in the event of harmful use of health data (as of any other data for that matter). We must prevent data on sex, origins, health status, etc., from being used by private or public companies to discriminate. It must not be permitted to sell, provide services or even contact people in a differentiated manner in other contexts than scientific research and health care. Illegitimate use must be strictly prohibited. Violation of the prohibition should be sanctioned by measures including full compensation of victims and prevention of recurrence.

An important aspect of health data being considered a public good, not a private good, is that it would be a provision that could not be opted out of. There would be no clause allowing health data to be sold, leased, exchanged, …. This prohibition would apply both to the patient data of a health institution and to an individual’s own data.

Of course, individual medical data should not be accessible to the merely curious. For everything not directly necessary for scientific research, a system of anonymization (or pseudonymization) should be implemented.

Conclusion: Sharing to improve longevity and resilience

It is now technically possible to share health data. The legal and logistical framework would be relatively easy to set up.

Imagine a world where health data cannot be used commercially, but only for your health and that of others. Imagine a world where the sharing of medical data would be systematic, instantaneous and usable by artificial intelligence. You and your doctor would know in seconds what medications people your age, in your region, with your medical characteristics are taking, what the best treatment is, based on knowledge gathered from around the world.

Imagine what should be the basic logic followed. Just as you can easily find on the internet what your favorite politician or singer did in July 2007, you could in one click find the medication you took three years ago, the blood test, the vaccinations, which you had done 15 years ago, the comparison with other populations, your allergies, predispositions, …

Imagine that all this data will allow tomorrow’s collective health research to be much more efficient, and clinical trials to be safer and faster.

Imagine a much longer and healthier life for everyone who wants it.

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This month’s good news: Towards restoring fertility in menopausal women

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A pilot study, conducted between 2017 and 2019 at the Genesis Fertility Clinic in Athens, Greece, enabled postmenopausal women to give birth. The experiment involved 30 women who had not had a period for more than a year, and 80% of them experienced an improvement in their hormone levels and returned to a regular menstrual cycle. Among them, four became pregnant and three had children. Fertility is said to have been restored with blood transfusions using the ovarian Platelet-Rich Plasma (PRP) method.

We have discussed the potential rejuvenating effects of transfusion in previous letters. Further research is underway to confirm that this fertility treatment is viable. Professor Pantos is supervising four randomized, placebo-controlled clinical trials and two other trials are being conducted by Professor Emre Seli at Yale Medical School.

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To learn more about it:

• See in particular: heales.org, sens.org, longevityalliance.org and longecity.org.
  
• Image Source.
  

The battle to feed all of humanity is over. In the 1970s hundreds of millions of people will starve to death in spite of any crash programs embarked upon now. At this late date nothing can prevent a substantial increase in the world death rate.

This is the certain fall in life expectancy following the overpopulation that Paul Ehrlich, author of the book « The Population Bomb », published in 1968 and which sold millions of copies, announced. Half a century later, the size of the world’s population has more than doubled. Even though hundreds of millions of people still suffer from hunger, we have never had so much food per person. And in terms of mortality rates, global life expectancy has increased by more than 15 years.

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Theme of the month: Overpopulation and Longevity

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Decline around 2064

It is time for some pessimists to put aside their images of doom about overpopulation. According to a recent study published in the scientific journal The Lancet, the world population will peak around 2064 at 9.7 billion people, and then begin a decline to 8.8 billion by the end of the century.

In the 1960s, each woman still had an average of 4.5 children, today this figure is less than 2.5. This is not much higher than the replacement rate of 2.1: the number you need to maintain a population.

As Swedish physician Hans Rosling writes in his book Factfulness: When parents see that children stay alive, that children are no longer needed for work, and that women receive an education and have access to contraceptives, both sexes, in all cultures and religions, begin to dream of fewer, but well-educated, children.

In 1950, 25 babies were born for each person who blew out 80 candles. Today, that number is about seven. If current trends continue, by 2100, for every person over 80 years of age, there will be only one baby. It is an invisible revolution, an inverted population pyramid, never seen before in history. It’s time to think about it, instead of wallowing in obsolete images of a supposedly inevitable explosion of the world’s population.

It is said that by 2100, 183 countries will not have the fertility rates needed to maintain the current population.

Today there are about7.8 billion of us. Demographers already knew that our population was expected to decline within a few decades, but this new study predicts that it will happen even faster than we thought.

The United Nations has also assumed that countries that fall below the replacement rate will stabilize at around 1.75 children per woman, but according to The Lancet, this estimate is based on a restricted sample. In countries such as Thailand, South Korea, and Greece, we find that the decline is continuing, at less than one and a half children per woman. And that makes a big difference in the long run.

Of course, a world of about 10 billion people remains a challenge, especially if we want everyone to benefit from the level of prosperity enjoyed in the West (one billion people don’t even have access to electricity yet). But with modern science and technology, this is certainly surmountable. More people even means, in many ways, good news.

A priori, it seems plausible that the more people there are, the fewer resources remain for everyone. However, from an economic point of view, this is not always true. More people often means less scarcity. Because many brains, densely packed together, come up with smarter ideas and become more specialized. The Simon Index of Abundance, named after economist and thinker Julian Simon, shows that raw materials become more abundant and cheaper as the world’s population increases. It sounds crazy and counter-intuitive, but this is often the case with scientific knowledge.

But beware, this can only be envisaged in the long run in a world where technological progress allows the use of mainly renewable energies and raw materials. This is technically possible, but it requires a political, social and economic will that is still insufficient today.

We must also temper the image of an overpopulated world. The surface of the planet is about 200 million square miles, 57 million of which is land. A country like Bangladesh is self-sufficient in food with more than 160 million inhabitants (one fortieth of the world’s population on one thousandth of the surface of the land mass).

By 2100, 183 of the 195 countries are predicted to lack the fertility rates needed to maintain current population levels, with a prediction of 2.1 births per woman, said researchers at the Institute for Health Metrology and Evaluation at the University of Washington School of Medicine. Some 23 countries – including Japan, Thailand, Italy and Spain – would see their populations decline by more than 50 percent.

However, the population of sub-Saharan Africa could triple, allowing just under half of the world’s population to be African by the end of the century.

The world, since the 1960s, has really focused on the so-called population explosion, » Dr. Christopher Murray, who led the research, told CNN. Suddenly, we’re now at that kind of turning point where it’s very clear that we’re rapidly moving from too many to too few.

More people over 80 will be over 80 than under 5 years old.

The study also predicts major changes in the global age structure as fertility declines and life expectancy increases. By 2100, an estimated 2.37 billion people worldwide will be over 65 years of age, compared with 1.7 billion under 20 years of age.

The number of people over 80 years of age in the world could be multiplied by six, from 141 million to 866 million. At the same time, the number of children under the age of five is expected to decrease by more than 40%, from 681 million in 2017 to 401 million in 2100. Childhood could become rare (article in French).

What about healthy longevity in all this?

First of all, it is necessary to recall, as was done as early as 2012 in a »Death of Death » letter (in French), that there is a strong correlation between life expectancy and fertility. In regions of the world where women and men live longer (and are better educated and more affluent), the birth rate is falling and the population tends to decrease. When life expectancy increases, the birth rate decreases and population growth is lower (or negative).

So the first good news is that longevity is a stabilizing factor for the population. To put it in a way that will appear provocative: to be fewer in number, let’s live longer!

Second good news: where people live longer, they tend to be more cautious. If one day, life expectancy becomes potentially much longer, well beyond a century, citizens will naturally be much more prudent, will invest more in their future and will not wish, for themselves or for others, an overpopulated planet.

There is, however, less good news. To this day, for populations beyond the age of 80 or 90, we still are not achieving significant progress in health. As already stated in previous letters, in terms of maximum lifespan, our progress is insufficient, particularly in terms of healthy longevity.

So, in the current state, overpopulation is not something that we are at risk of, on the contrary. However we do stand to havea world with a large population in fragile health. This is one of the many reasons why research for a much longer life in good health is fundamental, not only in the individual interest, but also in the collective interest.

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This month’s good news: Alzheimer’s disease is declining in Europe and the United States. Plasma and albumin to reduce the impact of Alzheimer’s disease. An enzyme prevents memory loss in mice.

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The risk of developing Alzheimer’s disease or another form of neuronal degeneration at a given age has been reduced by 13% in ten years, reports an important study conducted in the United States and several European countries. 

Beware, this good news is relative. Because of the increase in life expectancy, the number of people with Alzheimer’s disease is still increasing. In other words, the percentage of people affected in a given age group is decreasing, while the absolute number of people affected continues to increase.

In the field of Alzheimer’s disease research itself, a clinical trial to remove aging factors from the blood (by injecting albumin and immunoglobulin) is showing good results. This study is randomized and double-blind. It remains to be confirmed, however, especially since it is funded by a company producing albumin and immunoglobulin for therapeutic purposes.

In an article to be published in the journal Acta Neuropathologica, Lars and Arne Ittner, researchers specializing in the study of dementia at Macquarie University, detail how activation of a key enzyme (p38gamma) in the brain can prevent the type of memory loss associated with advanced forms of Alzheimer’s disease, and even reverse it. An important advance tested on mice, to be confirmed on humans.

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For more information, please visit:

• Heales.org, sens.org, longevityalliance.org and longecity.org.
• Image Source. 

Man has overcome the power of natural selection. He no longer adjusts to the conditions of external environment, but creates around him an artificial, beneficent environment, remaking nature. He does not need death as a factor accelerating the improvement of humanity from generation to generation. …

There are no theoretical prohibitions to raising the possibility of immortality. I am deeply convinced that, sooner or later, the era of longevity will arrive. … As in any task, enthusiasts are needed for this, unfortunately these are very few; we are hindered by the deep-rooted conviction that death is inevitable and that the struggle with it is futile. This is a sort of psychological barrier that must be overcome.

Vasily Feofilovich Kuprevich, microbiologist (1897-1969). Quoted by Ilia Stambler in A History of Life-Extensionism In Twentieth Century. 2014.

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Theme of the month: Blood and rejuvenation

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Some history

For thousands of years, blood has been one of the elements of the body with the strongest symbolic representation, representing in particular life, heredity (blood ties), fidelity (exchange of blood) and mechanisms of rejuvenation.

Considered to be one of the most ancient acts of medicine, bloodletting probably originated in Ancient Egypt, but also in the oldest traditions of India and the Arab world.

In Greece, Erastratus, in the third century BC, taught that diseases result from an overabundance of blood: the plethora.

In the second century AD, Galen professed that good health requires a perfect balance of the four « humors »: blood, phlegm, yellow bile and black bile. His writings and teachings made bleeding a common technique throughout the Roman Empire.

In medieval Europe, bloodletting became the basic treatment for all diseases, in particular, plague, smallpox, epilepsy and gout.

The technique then was to cut veins or arteries in the forearm or neck, using a special tool with a sharp blade.

Bleeding, as a medical procedure, became a little less distressing in the 18th century: doctors used spring-loaded lancets and an instrument called a scarifier, with several blades making parallel cuts.

Young blood 

What if the elixir of youth flowed through our veins? At least among those of us who have not yet dried up the source: the young. The hypothesis, which seems to come straight out of a vampire movie, is being studied more and more seriously since experiments have shown that blood extracted from an organism in the prime of life can regenerate bodies weakened by the weight of years. So much so that, in order to combat the many diseases associated with old age, the first patient transfusion trials have just begun.

A recent article by Harold Katcher and Steve Horvath, among others, concerns two-year-old rats that received blood plasma from young rats. Their physiological indicators during the test had almost become those of 6-month-old rats. This seems promising but this study is controversial, in particular because it does not test longevity and the rat sample is not sufficient to draw reliable conclusions. Moreover, this study has not yet been validated by the scientific community.

Already 15 years ago, this surprising lead in the quest for eternal or at least prolonged youth was opened up by the experiments carried out by Irina and Michael Conboy and their colleagues at Stanford University. “We wondered why all organs age at more or less the same rate, and we thought that the blood that connects them could be an explanation, » says Michael Conboy.

To test this, his team temporarily connected the vascular networks of young and old mice as if they were Siamese twins; a complex surgical procedure 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.

According to results published by an international team led by Tony Wyss-Coray of Stanford University, young blood could stimulate the production of new neurons in older mice. Meanwhile, an Anglo-American team, co-led by Amy Wagers, observed a regenerative effect in the spinal cord.

But where do these « alchemical » powers of young blood come from? Scientists have been trying for several years to identify the molecules that promote this regeneration. Experiments involving the injection of some of them have already produced promising results, and there is no shortage of avenues of research.

Where, on the other hand, may the molecules with the opposite action come from that gradually replace them in the blood over the years? We can imagine that certain tissues or organs, as they age, ‘infect’ others by producing more and more harmful molecules, which will travel through the bloodstream, says neurologist Tony Wyss-Coray. It remains to identify which ones.

The researcher shares the hope, with many colleagues, that inhibiting the action of these molecules linked to aging, and reinforcing the action of regenerative molecules present in young blood, could slow down the aging process.

While waiting for this Grail of life extension, the objective is already to prevent or treat the many chronic diseases favored by age (cardiovascular or neurodegenerative pathologies, bone and muscle fragility…), but also to promote organ regeneration after an accident or surgery.

And the first human trials have already begun. As early as 2014, Tony Wyss-Coray founded a start-up, Alkahest, which has since been giving weekly transfusions of a few deciliters of plasma, donated by individuals under 30 years of age, and bought from blood banks when they had a surplus, to 18 Alzheimer’s patients.

In 2019, the Wyss-Coray team published in Nature Medicine concerning a protein, VCAM1, which increases with age and seems to have a significant impact on the brain. Biological and cognitive measurements indicated that blocking VCAM1 not only prevented old plasma from damaging the brains of young mice, but could even reverse the deficits in older mice.

Diluted blood plasma

A new study, led by Irina and Michael Conboy of Berkeley University, has revealed an interesting new direction 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 older mice. The rejuvenation effects on brain, liver and muscles were the same or greater than in the first experiments in 2005. The procedure had no negative or positive effects on the health of the young mice.

Using proteomic analysis to study blood plasma and its protein content, the team discovered that the process acts as a « molecular reset button”. After the exchange, the team observed lower concentrations of pro-inflammatory proteins while beneficial proteins, particularly those that promote vascularization, were able to thrive.

“There are two main interpretations of our original experiments (from 2005), » explains Irina Conboy. The first is that in the mouse joining experiments, the rejuvenation was due to young blood and young proteins or factors that decrease with age, but an equally possible alternative is that, with age, you have an increase in certain proteins in the blood that become harmful, and these have been suppressed or neutralized by the young partners. As our (recent) experience shows, the second interpretation proves to be correct. Young blood or factors that are not necessary for the rejuvenating effect; dilution of old blood is sufficient.

Drug candidates

“Some of these proteins are of particular interest and in the future we may consider them as additional therapeutic and drug candidates » says Michael Conboy. “But I would caution against being overly optimistic. It’s very unlikely that aging can be reversed by changes in a single protein. In our experiment, we found that we could do a relatively simple, FDA-approved procedure that simultaneously altered the levels of many proteins in the right direction.”

So this is extremely promising. Unfortunately, only markers of aging were measured. No verification of progress in longevity was done since the mice were sacrificed once the experiment was completed. It may well be that the effects are only temporary or even negative over the long term.

However, a double-blind experiment on humans is said to be already being planned. It is very positive if this happens quickly and with well-informed volunteers. We would then quickly know whether there is as positive an effect on humans as on mice. We would know after a few months whether the positive effect is lasting. If it is, it will be a huge advance in longevity.

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This month’s good news: More and more international conferences for online longevity  

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Following the Covid-19 pandemic, a positive collateral effect is a wider, faster and often free dissemination of events concerning longevity. Thus the Life Extension Advocacy Foundation (LEAF – Lifespan.io) broadcasts numerous conferences, in particular via its YouTube channel.

Note for non-English speakers that it is possible to use automated translation for subtitling. It is still imperfect, but generally already understandable. A useful technological advance for many uses, including sharing information for a longer life.

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For more information, please visit:

• heales.org, sens.org, longevityalliance.org and longecity.org.

Source of the image.