Category Archives: The Death of Death

Monthly newsletter about life extension.

Newsletter. The Death of Death. October 2021. The Terror Management Theory.

We have long since (…) touched Mars, the Moon, harnessed nuclear power, artificially reproduced DNA, and now have the biochemical means to control births; why should death itself, « the last enemy », be considered sacred and beyond conquest? Alan Harrington, novelist, 1977 (The immortalist). 


Theme of the month: The Terror Management Theory 


Introduction

Terror Management Theory (TMT) was developed in the 1980s by Jeff Greenberg, Tom Pyszczynski and Sheldon Solomon. 

According to these authors, all human beings are confronted with two realities.

On the one hand, humans, like all animals, have an instinct to protect themselves and to try to survive. On the other hand, they have a higher level of self-awareness that allows them to understand, unlike other animals, that they are alive and that they will eventually die.

It undeniably involves the frustration of the desire to stay alive. This is both frightening and motivating, and represents a central and unique psychological conflict in human beings.

But this theory, already discussed in a letter The Death of Death from May 2010, also teaches us that man, in order to face the fear of death, has developed defense mechanisms. Knowing that we are not going to survive as individuals, we identify ourselves with the collective, our survival goals become collective goals. In a global vision, we could say that all forms of art, culture, tradition, long-term collective construction participate in this mechanism. It is a matter of valuing the culture of belonging that allows us to strengthen our self-esteem in the conviction that as individuals we contribute to building this sense.

Unfortunately, this mechanism also has negative aspects. By reinforcing group values, it encourages the rejection of those who are different. Here, as in other areas, fear is a bad counsellor, a counsellor of withdrawal not into oneself, but into one’s group.

How has Covid-19 influenced our reaction to death?

The coronavirus pandemic has reminded us how vulnerable we are, especially as we age. A fact we put out of our minds when times are less threatening.

Across the world, we have seen solidarity, but also withdrawal: some have mobilized to help others (e.g. making protective gear for caregivers or organizing fundraisers), others have stockpiled cans and toilet paper.

Some recent studies show that the perception of threat (Covid-19) is related to government decisions such as lockdowns (if the government orders lockdowns, the disease must be very serious) and to the number of reported cases. The increase in the number of cases in some countries would be correlated with the increase in conservatism and authoritarianism.

Only humans are affected

As already written, awareness of inevitability of the death is unique to humans. It is possible that some animals are aware of the death of their fellow creatures and the risk to themselves. Moreover, this awareness does not even concern all humans. Young children usually live a life that seems limitless to them with joy and without boredom.

Could it be human nature to learn how to die…

Neither the sun nor death can be looked at steadily, wrote La Rochefoucauld. To philosophize is to learn to die, as Socrates and Montaigne have said. No conscious adult human being is indifferent to the inevitability of his end. Faced with the passing of time, we feel, as on the edge of a precipice, fear, but also fascination. No civilization deals with the death of our fellow human beings without a specific approach.

Or could it be the nature of man to always struggle to overcome death?

Almost all civilizations, almost all religions, explain that death is not the end of the journey.  From an agnostic perspective, the main reason for beliefs in the afterlife is of course to deal with the fear of dying.  The search for immortality is found in beliefs, practices and rituals. Sometimes these are affirmations, incantations.  Sometimes they are methods that could be called « pre-scientific », instructions for avoiding death or for making death only a temporary phenomenon. 

For the Taoists, it was a matter of learning to live according to very ascetic methods. In ancient Egypt and Christianity as it was taught until recently, it was a matter of preserving the body, by embalming or burial to allow for the return, the reincarnation (return to the flesh). The Catholic Church refused cremation until recently.

An unconscious mechanism 

This is a fundamental aspect of managing terror. Our defences are constituted by what Ernest Becker called « The Denial of Death« . Faced with what is both unbearable and inevitable, we develop unconscious processes. If these processes were conscious, they would lose much of their effectiveness.

What about tomorrow, in a world where amortality becomes conceivable?

Living without unbearable fear is, of course, a desirable mechanism. But it can also be an obstacle to the struggle for healthy longevity, when unconscious mechanisms lead us not to fight against, or even to « love » death (from old age).

Collective ideals are the result of feelings of belonging to groups that were initially opposed to each other. Today, they allow us to behave in an increasingly global community to live in a more peaceful, more united and more sustainable way, especially in the fight against global warming. In the same way, tomorrow, a better « management of the fear of death » could allow us to make better progress towards a much longer healthy life, even one day without time limits.


Good news of the month


  • Although this is a fragile development, mortality from the Covid-19 epidemic is slowing down. While the number of people affected continues to rise, the number of deaths both in Belgium and worldwide is decreasing, showing the increasing effectiveness of preventive vaccines and therapeutic treatments.
  • Among the most promising treatments for the coronavirus, molnupiravir is providing renewed hope: the tablet is believed to halve the risk of hospitalization or death in Covid-19.

For more information:

Newsletter. The dead of the dead. N° 150 September 2021. Microbiome and longevity

« But there is every reason to believe that adding Triphala and these probiotics to the diet is a guarantee of longevity and health. »

Satya Prakash (Biomedicine and Cellular Therapy Research Laboratory, Department of Biomedical Engineering, McGill University, Canada) (note: this is only about moderate improvements in healthy life span with better nutrition). 


Theme of the month: Microbiome and healthy longevity


Introduction 

Our body is made up of complex, fascinating, interdependent and changing systems.

All of them vary throughout the ages of life and, unfortunately, gradually deteriorate. 

The digestive system is the one that most directly confronts the outside world, the most changing, hostile and dangerous environment.

Every year, nearly a ton of food and drink, but also kilos of medicines, non-nutritive substances and millions of billions of bacteria, viruses and parasites pass through it and sometimes settle in it. As humans are omnivores, the diversity is particularly great. This is one of the reasons why research approaches to longevity are also diverse.

The importance of the gut microbiota

Our body is home to many different bacterial species. These communities of microorganisms, called « microbiota« , take up residence in different parts of our body: the mouth, the skin, the vagina… But above all the intestine! This organ, which is about 8 meters long, is home to up to 100,000 billion bacteria, mainly located in the small intestine and the colon. Scientists estimate that nearly 90% of fecal matter is made up of bacteria!

These bacteria, associated with other microorganisms such as viruses and yeasts, form the intestinal flora, now renamed « gut microbiota » by the scientific community.

In utero, the fetal digestive tract remains a sterile environment. During birth, breastfeeding and dietary diversification, the intestinal microbiota of an individual builds up over the years, until it contains nearly 1,000 different bacterial species in a healthy adult. A bacterial world that weighs nearly 2 kilos.

The 200 million neurons of the digestive tract

The same neurons as those in our brain line our digestive tract, some people call it a « second brain« ! 

The primary function of the enteric nervous system is to ensure the motor function of the intestine. The nerve cells are also responsible for transmitting information from our intestine to our brain. In addition, like the brain, the neurons of the intestine are able to produce hormones and neurotransmitters. 

Our emotions are also lodged in our intestines. Being « scared to death » or « having a knot in your stomach », « digesting information » are expressions that illustrate realities.

Links between Alzheimer’s disease and the microbiome have been established by studies. On the other hand, it does not seem that the neurons of the « second brain » suffer from a specific Alzheimer’s or neurodegenerative disease, even if the nervous control degrades with age (one of the causes of incontinence in the elderly).  

Could the microbiota and the gut be the key to improving longevity?

Recently, variations in the gut microbiota have been associated with age-related phenotypes and probiotics have shown promise in managing the progression of chronic disease. 

In a scientific paper published in Nature in May 2018, researchers highlight a longevity extension in Drosophila. By adding a combination of probiotics and a plant-based supplement to the diet of Drosophila flies, scientists at McGill University were able to extend their lifespan by 60% and protect them from chronic diseases usually associated with aging.

In this study, novel probiotic and symbiotic formulations were shown, in combination, to extend longevity in male Drosophila melanogaster through gut-brain communication mechanisms with implications for chronic disease management.

Longevity in mice

Researchers discover the potential of microbes to slow brain aging

Research from the APC Microbiome Ireland (APC) SFI Research Centre at University College Cork (UCC) published in Nature Aging presents a new approach to slowing aspects of age-related brain and cognitive deterioration via gut microbes. This research opens up potentially new therapeutic avenues in the form of microbial interventions to slow brain aging and associated cognitive problems.

There is a growing appreciation of the importance of microbes in the gut to all aspects of physiology and medicine. In a very recent study in mice, the authors show that by transplanting microbes from young animals into older animals, they could rejuvenate aspects of brain and immune function.

The researchers explained in the journal Nature Aging, « The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process leads to dramatic alterations in microbiota, which are linked to poorer health and frailty in older populations. Transplantation of microbiota from young donors reversed age-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and aging transcriptome of recipient mice. »

Longevity in humans

A recent study by the Institute for Systems Biology (ISB) shows that depending on the type of intestinal microbiota (the composition of the microbial flora that permanently inhabits our intestines), we age in better or worse health. This would therefore have an impact on longevity.

The microbiota changes after age 50

The researchers analyzed the gut microbiota and health status of more than 9,000 people aged 18 to 101, with a particular focus on the 78+ age group. In the latter group, they found that the microbiota changes in composition as we age and becomes more and more « unique » but that the different microbiota of healthy people all perform similar metabolic functions.

Our bacteria produce anti-aging substances

In correlation, higher concentrations of certain metabolites produced by the microbes in the intestines were measured in the subjects’ blood. Thus, it seems that changes in intestinal flora in healthy aging are linked to the production of certain metabolites whose effect on longevity is known, such as indole for example.

It is known that certain types of intestinal bacteria convert tryptophan (an essential amino acid) into indole, which passes into the bloodstream. It has been shown that indole prolongs life in mice and reduces intestinal inflammatory processes.

Another microbial metabolite, phenylacetyl glutamine, is found in large quantities in the blood of centenarians.

To conclude, it is noted that the microbial flora, continuing to evolve at an advanced age, would make it possible to better preserve health and to improve longevity, it is in relation to the common production of certain metabolites (like the 2 examples quoted previously). These modifications would be done especially after the fifty years.

Changes in microbiota with age

While the composition of our microbiota remains relatively stable during adulthood, changes in diet, even medication (antibiotics, anti-acids, …), the slowing down of gastrointestinal transit and digestion … lead to an imbalance of the digestive flora as we age

The diversity of bacterial species tends to decrease with age. Among other things, there is an increase in enterobacteriaceae and germs that can then become pathogenic by their number, such as streptococci, staphylococci, etc. These develop more easily in an inflammatory environment, and will themselves maintain a localized inflammation, as well as a too great permeability of the intestinal mucous membrane.

It has been observed in people over 105 years old, an increased presence of certain bacterial families (akkermansia, bifidobacteria and christensenellaceae). This suggests that this presence appears to favor the control of inflammation and a better maintenance of immunity, in spite of repeated stress and the constant work of defense of a whole life, against foreign microbial elements.

For example, bifidobacteria represent nearly 90% of the bacteria of breast-fed infants, and only 5% at the end of life. Their contribution seems beneficial in several ways in the elderly, according to studies.

It would be possible to define a person’s age by studying the composition of their microbiota 

Longevity researcher Alex Zhavoronkov and his colleagues from artificial intelligence startup InSilico Medicine analyzed the DNA of the gut microbiota of healthy people from different countries. A total of 1165 people between the ages of 20 and 90 were enrolled in the study and more than 3600 stool samples were collected to study the gut microbiota data and enable the tool to be trained.  The machine was able to give the age of the individuals with a margin of error of only 4 years!

Moreover, of the 95 bacterial species studied, 39 of them could predict age. The researchers were also able to show that certain species of bacteria were more abundant as we aged, such as Eubacterium hallii, which is associated with a healthy balance of intestinal metabolism; and others, on the contrary, were in smaller quantities, such as Bacteroides vulgatus, which is correlated with ulcerative colitis.

What about tomorrow?

So far, very different diets (without excess) and microbiota lead to relatively similar maximum lifespans. A Japanese and a French person have a very different diet, but a similar longevity.

However, further research, particularly the analysis of genetic data from the countless organisms that populate our digestive organs, opens up significant prospects for longevity. Among the leads, those influencing the nervous system are among the most important. 


September News


Aubrey de Grey, the world’s best known biogerontologist, helped the SENS organization raise $28 million. Immediately afterwards, on the basis of harassment charges, he was expelled from SENS, among others. However, at the time of writing, none of the thousands of women and men, minors or adults, who have been in public or private contact with him for decades have, to our knowledge, taken legal action. Whatever the

media’s temptation and the pressure to condemn without procedure, and while respecting the rights and opinions of everyone, including the alleged victims, we will stick to fundamental human rights: Everyone accused of a criminal act is presumed innocent until proven guilty in a public trial in which he or she has been given all the guarantees necessary for his or her defense.

American billionaire and philanthropist Yuri Milner has announced the creation of Altos Labs, a company that aims to make radical advances in human longevity with funding in the hundreds of millions of dollars. Jeff Bezos is also widely quoted as a co-founder. Renowned scientists specializing in aging research have been recruited or associated, including epigenetic clock specialist Steve Horvath, Nobel laureate Shinya Yamanaka and Spanish rejuvenation researchers Juan Carlos Izpisúa Belmonte and Manuel Serrano


 For more information:

Heales Monthly Letter The Death of Death N° 149. August 2021. Longevity and altruism

« And so, if for millennia the task of common men and daydreaming philosophers alike had been to ask, “What happens if we die?”. Today we’re tasked with a goal far more challenging: that of examining what happens if we live. […] What if, for the first time in history, we’re building a civilization that relies not on death, but on the deployment of ethical technologies, for its enhancement? » Raiany Romanni, bioethics researcher, Harvard Medical School. Source.


Theme of the month: Longevity and Altruism  


Introduction

The importance of wanting the good of others, for the sake of others (and not for any religious reason or moral obligation) is a concept that is far more important today than it was yesterday. The word altruism itself is less than two centuries old. It was created by Auguste Comte, as an antonym of the word egoism, in 1850. In this letter, we will not address philosophical questions about the deep reasons for altruism. What is important in this letter is that conscious solidarity is one of the reasons for the enormous social progress and longevity. Thus, never in the history of humanity have we been more concerned about others, starting with the elderly and therefore the weakest, than during the current Covid epidemic.

Altruism in animals

Altruism does not only refer to the conscious mobilization of humans for others. In biology, altruism refers to the behavior of an individual that increases the selective value of another individual while decreasing its own abilities. Altruistic behaviors in biology appear most obviously in kinship relationships, such as kin selection. They can also be observed in larger social groups, such as in social insects.

They allow an individual to increase the transmission success of his or her genes by helping related individuals who share those same genes.

Obligate altruism is the permanent loss of direct  fitness (reproductive) (with the potential for indirect gain). For example, worker bees may forage for food for the colony (individual cost, but collective gain).

Optional altruism is a temporary loss of direct capacity (with a potential indirect gain from personal reproduction). For example, a Florida scrub jay may help at the nest, then gain parental territory.

Examples:

  • Wolves and wild dogs provide meat to pack members not present at the kill. 
  • Mongooses support old, sick or injured animals.
  • Meerkats often have a guard to warn of predator attacks while others are feeding.
  • Male baboons threaten predators and cover the rear while the herd retreats.
  • Bonobos have been observed helping other injured or disabled bonobos.
  • Vampire bats usually regurgitate blood to share with unlucky or sick roosting companions who have been unable to find a meal, often forming a « buddy system. »
  • Lemurs of all ages and both sexes will care for infants that are not related to them.
  • Dolphins support sick or injured animals, swimming under them for hours and pushing them to the surface so they can breathe.
  • In many bird species, a breeding pair receives support in raising their young from other « helper » birds, including help in feeding their chicks. Some will even go so far as to protect the young of an unrelated bird from predators.

Being altruistic may be good for your health!

What if helping others was not just an altruistic gesture? A study published in 2006 in Evolution and Human Behavior suggests that helping children, grandchildren, or more distant relatives may give a boost to longevity.

Scientists at the University of Basel in Switzerland studied 500 people aged 73 to 103. They found that those who cared for their grandchildren lived longer than those who did not: half of the caregivers were still alive 10 years after the study began, while half of the less devoted grandparents died within five years.

In the absence of grandchildren, direct assistance to children, such as housework, has the same effect on longevity. Prosocial behavior by grandparents towards children and grandchildren appears to set an example of altruism for future generations and inscribe this model in their nervous and hormonal systems.

Be careful, however, it is also possible that the differences can be explained by the fact that only healthy grandparents can take care of their grandchildren, because people in poor health have fewer children and therefore fewer grandchildren, less contact, fewer activities…

According to American researchers, the feeling of well-being acts on our genes and boosts our immune system. But happiness is differentiated into two different types and only altruism seems to be able to influence the human epigenome.

 The immune system of altruistic people is found to be more developed than that of people experiencing hedonic well-being (i.e., cultivating one’s own emotions in order to feel happy), researchers reveal in their study published by the scientific journal Proceedings of the National Academy of Sciences (Pnas)

Specifically, after taking blood samples from 80 healthy volunteers, the researchers observed that the human genome seems to respond to a positive psychological state. In case of altruism, inflammatory genes decrease and antiviral genes increase, in order to protect the body.

Effective Altruism

The phrase « It’s the thought that counts » sounds nice, but it is actually morally untenable. Our altruistic actions must be measured by their effectiveness. Effective altruists advocate that we should estimate the « cost-benefit » of our actions to others. For example, providing food worth a certain amount of money may be less altruistic than investing the same amount in better agricultural production by farmers.

In the health field, funding care and medication to reduce the effects of age-related diseases is a useful act, but less so than funding research to end these diseases.

Of course, the outcome of these investments is not certain and the benefit is longer term. Most often, effective altruists invest in projects that are relatively easy to measure and therefore not in wide-ranging efforts such as research. Yet, the benefits of wide-ranging advances are considerable. One euro for care in a nursing home will benefit a few people. One euro for a therapy for a healthy life can benefit all.

The duty of altruism

Helping your fellow man in certain circumstances is a duty for most philosophical and religious currents. It is also a legal obligation whenever a person is in danger in some countries such as France or Germany. This is called the duty to rescue.

 There have been cases where people have been prosecuted for this type of crime because they did not act correctly in view of scientific progress. If the demand and social pressure became strong enough, we could likewise consider it a crime not to invest in research for healthy longevity. The State, at least, could be legally, even constitutionally, ordered to make these investments (in the same way that it is today ordered to guarantee the health of its citizens).

 Note that the fact that the outcome of the assistance is uncertain does not absolve the duty. A person who refuses to help an injured person cannot justify himself by saying that he would probably have died anyway. Therefore, the fact that the outcome of the search is uncertain does not mean that there is no duty.

 In France and Belgium, case law generally considers that only the effect requiring immediate action should be considered. But this could change.

Long-term altruism

Many citizens, especially environmentalists, rightly insist on concern for future generations. In fact, it is also about current generations, because climate change and pollution will already have impacts in our lifetime. They even have some today. But the concern, the altruism for the future, is also to offer a healthier and much longer life to the children who will be born tomorrow.

Finally, we could say that there is even a form of altruism towards this other person who is oneself in the long term. Many of our behaviors are a choice between short-term interest (« bad » eating, smoking, distraction…) and long-term interest (exercise, study…). The choice to work for a longer and healthier life is in my opinion an altruism for one’s future self.


Good news of the month. Potentialities of gene therapies.


It is the genetic heritage that determines quite precisely the maximum lifespan of a human, any other mammal and most animals. The potential of gene therapies for longevity is expanding and becoming clearer. Renowned scientist George Church gave an interview on this topic for the organization Lifespan.io.

 


For more information

See: 

The death of death N° 148. July 2021. Biomarkers and longevity

« Deep biomarkers of aging developed from various types of aging data are rapidly advancing the longevity biotechnology industry. The use of biomarkers of aging to improve human health, prevent age-related diseases, and extend healthy life spans is now being facilitated by rapidly increasing data acquisition capacity and recent advances in AI. They offer great potential to change not only aging research, but healthcare in general, » said Polina Mamoshina, a scientist at Insilico Medicine.

Theme of the month: Biomarkers and longevity

A biomarker is a measurable biological characteristic related to a normal or abnormal process.

In the medical field, a biomarker can be any measurable biological indicator. They can be quantitative or qualitative. Qualitative biomarkers could be involved in detecting a disease process in a yes/no analysis, while quantitative biomarkers are involved in detecting a disease process with a threshold effect. Most diagnoses are based on biomarkers.

Biomarkers and aging

Biomarkers are of growing interest, as they allow the measurement of aging, not on a one-off basis (as is the case with biological age), but on a continuous basis, resulting in a new measure: the rate of aging. Researchers have summarized the biomarkers of aging into different subcategories:

Biomarkers known as »genetic criteria »

The appearance of somatic DNA mutations during aging suggests that the measurement of genomic instability (the loss of the ability to repair DNA during cell divisions) could be a biomarker of aging.

With regard to telomere length, this is decreased with aging. Telomere shortening is explained by a decrease in telomerase activity. The measurement of telomerase enzymatic activity in human cells could be informative to assess aging.

Cellular senescence, the « pausing » of certain cells in response to cellular damage, is a protective mechanism that is increasingly used throughout the aging process. The measurement of cellular senescence is reliable and informative for assessing biological aging.

The increase in the number of epigenetic modifications such as DNA methylation, histone modification, the presence of non-coding RNA, appear during aging. These measurements, known as « epigenetic clocks » have been studied in particular by Steve Horvath.

Repair of cellular damage (damaged macromolecules, organelles) is a key process in maintaining cellular integrity and function. Autophagy capacity decreases with age, resulting in the accumulation of non-functional damaged proteins. Assessing the mechanisms of repair, recycling, and removal of damaged macromolecules could be a measure of biological aging.

Mitochondrial dysfunction, i.e. a weakening of the energy production mechanisms in our cells and of the capacity to manage oxidative stress by the mitochondria, are other interesting markers.

Finally, the evaluation of stem cell depletion, of nutrient sensing dysfunction, and alteration of intercellular communication could also be useful biomarkers to evaluate the aging of an individual.

Biomarkers known as « biological criteria

Abnormal levels of these « markers » indicate an accentuated aging of the organism, and they are, for the most part, linked to a shorter lifespan and a higher risk of disease.

With an anti-aging evaluation, it is possible to evaluate the stage of aging. These biomarkers are classified according to the functions most often altered in aging:

Glycemia and insulin resistance

Aging is associated with a disturbance in glucose metabolism. Disturbances in the regulation of blood sugar levels and insulin spikes are often present in aging-related phenomena.

Biomarkers such as glycated hemoglobin (HbA1c), fasting insulin level and the HOMA index (= insulin*glucose / 22.5)… are indicators reflecting the general state of glycation of tissues, a major phenomenon of aging.

Adiponectin: this recently discovered hormone is correlated with the mechanisms of inflammation. Studies have shown that it steadily decreases with advancing age and has strong links with the onset of metabolic syndrome, diabetes, atherosclerosis and non-alcoholic fatty liver disease.

– Vitamins and minerals

Vitamin D: A study of 10 different populations showed that relatively high levels of vitamin D were associated with a decreased risk of all-cause mortality. Diseases related to aging and vitamin D include osteoporosis and Alzheimer’s.

Vitamin B12: Vitamin B12 levels often decline after age 50. Low levels are correlated in various studies to a higher risk of cognitive dysfunction, dementia and coronary artery disease.

Calcium: it has been shown that advancing age is often linked to a calcium deficit (leading to osteoporosis, among other things). This deficiency is thought to be due to vitamin D deficiency and also to a decrease in intestinal calcium absorption.

Zinc: Zinc deficiency is common in the elderly, due to dietary deficiencies and/or poorer intestinal absorption. It leads to phenomena similar to those observed with the oxidative inflammation of age and immunosenescence (degradation of defenses).

Selenium: A high blood level of selenium is generally correlated in studies with decreases in cancer risk.

Albumin: best known as a biological marker of protein-energy malnutrition, it is also a marker of aging that tends to decrease with age.

Creatinine and urea: they allow the evaluation of a weakening of the renal function.

Chronic inflammation, which generally increases with age, is the best-studied field in immunosenescence. Elevated plasma levels of leukocytes, interleukin 6 (IL-6), and TNF-α (tumor necrosis factor) correlate with loss of grip strength.

Ultra-sensitive C-reactive protein (CRP): this marker of inflammation is correlated with lifespan according to a study of 90,000 people. Lower levels of CRP are associated with greater longevity.

– Hormones

Testosterone: Testosterone levels decline steadily with age.

IGf-1 (insulin-like growth factor 1): the marker for growth hormone. Its decline is associated with aging, called « somatopause ».

Sex Hormone-Binding Globulin (SHBG): as we age, SHBG levels increase by about 1% per year. The decrease in androgens and the excess of estrogens increase the production of SHBG by the liver.

Cortisol: The level of cortisol, the stress hormone produced by the adrenal glands, is correlated with age-related diseases. The more abnormal its secretion, the more glucose metabolism is disturbed.

Dehydroepiandrosterone (DHEA): DHEA sulfate is well known to decrease in blood levels with age in both sexes from the age of 30. One study reported an average decrease of 5.2% per year.

Pregnenolone: generally decreases with age, especially between the ages of 35 and 50 where its level frequently drops by 60% or more. Pregnenolone allows better resistance to stress and is very much involved in cognitive functions and memory.

– Lipids and fatty acids

Disturbances in blood lipids are among the most reliable markers of cardiovascular risk and mortality. Triglycerides and cholesterol will therefore be classic markers in the monitoring of aging.

Free radicals can damage our DNA by oxidizing nucleic bases. These reactions leave traces: a fragment of oxidized base called 8-hydroxy-2-deoxy-guanosine (8-OHdG).

Biomarkers called « physical criteria

You don’t wake up one morning with gray hair and a cane. Old age is a long process of biological changes.

– The senses

The loss of autonomy generally occurs after the age of 70. It is explained by cognitive, physiological, muscular and articular changes, the first symptoms of which appear between the ages of 40 and 50.

The first sign is presbyopia. At an average age of 44, vision is affected by a loss of accommodation between distance and near vision. Around the age of 60, it is hearing that is affected: presbycusis. 34% of people over 60 have difficulty hearing. The three other senses are then affected: touch, taste and smell.

– The physical and the mental

With old age, the structure of the brain and nervous system changes. With age, these cognitive changes lead to psychomotor slowing down, an alteration of attention or of short-term memory.

The decrease in physical capacities (gripping strength, speed of movement, etc.) are simple and fairly reliable indicators of aging.

Old age brings about other physiological changes such as weight gain, changes in the hair system (gray hair and baldness), drying and degradation of the skin (wrinkles), a decrease in immune resistance or even the loss of teeth. Even the percentage of water in our body decreases.

Is it useful to improve the indicators?

Many therapies aim to improve certain biomarkers. For example, gene therapies for telomerase or hormone cocktails to compensate for age-related decreases.

However, it is not necessarily established that the indicators of aging are also influencers. In some cases, it is very likely that they are mainly an effect (e.g. gray hair). In many other cases, therapies aimed at influencing the indicator should have therapeutic effects. If an indicator changes favorably, the impact will be to some extent favorable to healthy longevity.

We have more and more information about biomarkers and how our actions, therapies etc. influence them. New experiments are not always needed to understand them better. We can use the immense resources of health measures already available through retrospective studies and through the monitoring of ongoing therapies. The more rigorously we use them, the easier it will be to assess and to achieve progress towards longevity.

Many good news this month.

Aubrey de Grey, the iconic leader of SENS, the most renowned and probably the most effective organization in the fight against aging, has announced the receipt of donations totaling approximately $20 million, several times the organization’s annual budget.

Laurent Simons, a gifted Belgian who recently graduated from university at the age of 11, has one ultimate goal: to enable the « immortality » of his grandparents, among others. And that’s why he studies! 

Vitalik Buterin, developer of the Ethereum crypto-currency and a young, gifted billionaire, publicly announces his passion and investments in longevity.

The BioViva organization, presented by Elisabeth Parrish, announces a gene therapy experiment giving excellent results for longevity in mice.

The United Kingdom announces in an official document entitled « Life Science Vision« : <<[…] there is now a wealth of literature on potential pathways and targets that could be used to address the most inevitable cause of disease in human populations.>> (translation) »

The United States clarifies Joe Biden’s stated goal of developing an agency that will address diseases in innovative ways. The name of this future organization is ARPA-H (Advanced Research Projects Agency for Health).

For more information:

The death of death N°147. June 2021. Longevity records of living organisms

Scientist Shin Kubota expresses his vision in the New York Times: « Turritopsis application for human beings is the most wonderful dream of mankind,” he told me the first time I called him. “Once we determine how the jellyfish rejuvenates itself, we should achieve very great things. My opinion is that we will evolve and become immortal ourselves.”. » (November 28, 2012)


Theme of the month : Longevity records of living organisms


Tortue des Galapagos

How to understand the longest lifespan? And why? 

The maximum lifespan of living things is extremely variable depending on the species. Overall, for animals, the maximum lifespan is longer with one or more of the following favorable factors:

  • Predators are rare 
  • The metabolism is slow 
  • Size is large

The differences in lifespan can be enormous between species that are biologically quite close. This is one of the reasons to consider gene therapy or other medical treatment to dramatically increase the maximum lifespan of humans.

This letter includes known cases of extreme longevity. Obviously, in these cases of very long lifespans, only indirect and sometimes questionable measures are possible.

The naked mole rat and the bat, exceptional longevity and no cancer! (35-40 years)

The longevity of naked mole rats is especially surprising when compared to other captive rodents of similar size. Naked mole rats are not expected to live more than six years. However, the oldest naked mole rat known in the laboratory is… 35 years old! And, among some of its fellow rats that are over 30 years old, some females are still fertile.

Researchers have discovered why naked mole rats are cancer-free. It is thanks to hyaluronic acid, a molecule that is thought to prevent the formation of tumors in the body. According to researchers Vera Gorbunova and Andrei Seluanov, who published their results in the journal Nature, the molecular weight of hyaluronic acid in the naked mole rat is five times greater than in mice.

The tiny Brand’s bat, at seven grams, lives for almost forty years. It is the same for the great mouse (Myotis myotis), which is five times heavier. An international team undertook a longitudinal study over eight years. Their results, published in the journal Nature Ecology & Evolution, open up promising avenues for research on aging.

Longest-lived insect: the termite queen (50 years)

Insects are normally thought of as living less than a year as adults. However, termite queens, protected from predators, can reach 50 years.

Birds: The albatross can live up to 80 years

Albatrosses are the largest seabirds in the world: the howler albatross reaches a wingspan of 3.50 meters! Their longevity is also remarkable, as they can live up to 80 years. Wisdom, a 70 years old albatross has laid eggs again. A parrot (cockatoo) has also reached a similar age (82 years).

Oldest amphibian: the cave salamander (100 years)

Naturalists attribute the longevity of the blind salamander Proteus anguinus to its unusually slow metabolism. Tthis salamander takes 15 years to mature, mates and lays eggs only about every 12 years, and barely moves except when foraging for food. In addition, the damp caves of southern Europe where it lives are virtually free of predators, allowing P. anguinus to live beyond 100 years in the wild.

Reptiles: The famous Galapagos tortoises

In 2012, « Lonesome George » died at over 100 years old. Six years after his passing, the centenarian has made a comeback thanks to the revelations of Yale researchers studying his genome! George was the last representative of a species endemic to a Galapagos island. He always shunned any mating in captivity. The scientists who had sequenced his genome during his lifetime as well as that of another species of giant tortoise, revealed the results in the journal Nature.

The biologists detailed 891 genes in these turtles, involved in the function of the immune system. They show that these animals have developed extra copies of genes that allow them to better respond to oxidative stress, known to be a major factor in aging. They also discovered a gene that allows cells to better defend themselves against foreign cells, as well as tumor suppressor genes that are more numerous than in most vertebrates, and others that are involved in DNA repair.

The study of aging in animals is a source of knowledge for humans. Researchers have found some similarities between the genomes of turtles and centenarians.

Jeanne Calment with her 122 years is the person who lived the longest in the history of humanity…, but certainly not enough to impress an old turtle. The longest living turtle seems to have reached 189 years of age.

Sphenodons are other reptiles that can live past a century.

Fish: 150 years for the orange roughy (Hoplostethus atlanticus)

Hoplostethus atlanticus is called « watchfish ». The animal lives in the world’s oceans at depths between 900 and 1,800 meters, especially in submarine canyons.

The species only reaches sexual maturity between 20 and 30 years of age, which could be explained by a low predation rate and the scarcity of prey in the abysses. Adults can measure 75 cm long and weigh 7 kg and the age of the oldest known specimen, determined by radiometric radiation of the mineral accumulations in its internal ears, is said to  be 149 years.

Echinoderms: 200 years for the giant red sea urchin (Astropyga radiata)

Quite common in the Indian Ocean and in part of the Pacific Ocean, this echinoderm owes its name to its color and its size, which can reach nearly 20 cm in diameter, the largest known among sea urchin species. Some individuals have reached the age of 200 years.

Mammals: 200 years for the bowhead whale (Balaena mysticetus)

Living in Arctic waters, the bowhead whale is a cetacean measuring up to 20 meters and weighing around 100 tons. Its longevity has been estimated at more than 200 years thanks to scars left by old wounds caused by whale hunters. This exceptional longevity could be explained by certain genes. For example, analysis of the whale genome shows unique mutations in the ERCC1 gene involved in the repair of damaged DNA. Another gene, called PCNA and associated with cell growth and DNA repair, contains a duplicate section of DNA. This duplication could slow down cetacean aging.

Sharks: 400 years for the Greenland shark (Somniosus microcephalus)

This rather plump grey shark, measuring five meters, lives in the waters of the Arctic Ocean and is the champion of longevity among vertebrates. Its growth is estimated at about 1 cm per year.

In an article published in Science, an international team of researchers describes how they managed to measure the age of 28 Greenland sharks. The results revealed that the largest shark, a female over five meters long, was 392 years old, although there is a significant margin of error of plus or minus 120 years. The sexual maturity of females is thought to be reached at the age of about 150 years.

According to this research by Julius Nielsen at the University of Copenhagen, published in August 2016, the Greenland shark would therefore be the longest-living vertebrate.

Oldest Mollusc: The Ocean Quahog (500 years)

Scientists have determined that the ocean quahog, Arctica islandica , can literally survive for centuries, as demonstrated by one individual, Ming, which has surpassed the 500-year mark (you can determine a mollusk’s age by counting the growth rings in its shell).

Trees. The Giant Sequoia: over 3000 years old!

Some trees seem to have no senescence mechanism. They remain as fertile at the age of several centuries as in their youth.

The Giant Sequoia is characterized by its longevity since it can reach more than 3000 years. 

Many other species of trees can live for centuries: olive trees, oaks. The absolute record seems to be held by a 5,000 year old Bristlecone pine.

Finally, trees, like other plants, can multiply clonally and form a collective organism. In this sense, the clonal colony of aspen Pando is, at 80,000 years, one of the oldest organisms on the planet.

Microscopic organisms: endoliths (10,000 years)

Determining the lifespan of a microscopic organism is a tricky question: in a sense, all bacteria are immortal, as they propagate their genetic information by constantly dividing (rather than having sex and dying of age).

The term « endoliths » refers to bacteria, fungi, amoebas, or algae that live deep underground in cracks in rocks. 

Studies have shown that individuals in some of these colonies undergo cell division only once every hundred years and can have a lifespan of about 10,000 years. 

Technically, this differs from the ability of some microorganisms to recover from stasis or freezing after tens of thousands of years; in a significant sense. Endoliths are continuously « alive », though not very active. Perhaps most importantly, endoliths are autotrophic, meaning that they fuel their metabolism not with oxygen or sunlight, but with inorganic chemicals, which are virtually inexhaustible in their underground habitats.

Biological immortality in lobsters, hydras, sponges and corals

A small number of multicellular animals seem to have no mechanism of senescence. They do not degrade as they age. For example, their fertility remains constant or even increases.

Hydras, like all cnidarians, can regenerate, which allows them to recover from an injury and reproduce asexually. All hydra cells divide continuously. It has been suggested that hydras do not undergo senescence and, as such, are biologically immortal. In a four-year study, three cohorts of hydras showed no increase in mortality with age.

One species of sponge can live up to 11,000 years, namely Monorhaphis chuni, according to a U.S. study published in the journal Aging Research Reviews in 2014.

Some colonial animals, such as corals, can live more than 4,000 years.

Research suggests that lobsters may not slow down, weaken or lose fertility with age, and that older lobsters may be more fertile than younger lobsters. This does not, however, make them immortal in the sense of no impact of senescence, as they are much more likely to die in a shell molt with advancing age due to their increasing size. 

Their longevity may be due to telomerase, an enzyme that repairs long repetitive sections of DNA sequences at the ends of chromosomes, called telomeres. Unlike vertebrates, lobsters express telomerase in adulthood throughout most tissues, which has been suggested to be related to their longevity.

It has been claimed that some fish, notably the bigmouth buffalo, do not have measurable senescence. However, with the exception of the Greenland shark, no captured fish whose age was measured exceeded 200 years.

Why no biological immortality in vertebrates, even those without predators?

Natural selection, at least for vertebrates, always results in species with limited lifespans. This can be explained by the fact that an animal species without aging would lose its genetic diversity and be eliminated by any environmental change. This also explains sexual reproduction: more genetic mixing means more adaptability to the environment. 

But in a certain sense, systematic aging remains an evolutionary mystery. Indeed, even salamanders or cave fish in an extremely stable environment (hundreds of thousands of years) and without predators do not seem to live much beyond a century.

Cnidaria: biological immortality and rejuvenation for the jellyfish Turritopsis nutricula

Small in size, but long in life expectancy. The jellyfish Turritopsis nutricula measures only 5 mm in diameter, but could live ad vitam æternam. Native to the Caribbean Sea, the species is nowadays very widespread. Several specialists are worried about its proliferation over the whole globe.

Thanks to a particular cellular process called transdifferentiation, the animal is able to stop its aging and even to become younger. It is already known that the best way to push a Turritopsis Nutricula to regenerate is to stress it. For example, in case of an injury, the process starts immediately and within a few days, the jellyfish returns to its juvenile stage and starts a new life.

This makes it an exceptional subject of study for biologists and geneticists, and a subject of interest for some pharmaceutical groups who are already considering the production of a rejuvenating cream containing Turritopsis DNA. « It’s as if a butterfly were able to go back to the caterpillar stage, » says Stefano Piraino, a professor at the University of Salento in Italy.

Dormancy as a longevity strategy

Dormancy is a term that covers all forms of slowed life. 

It is the period in the life cycle of an organism when growth, development and/or physical activity (in animals) are temporarily stopped. This reduces metabolic activity and thus helps the organism to conserve energy.

Especially in extreme environments, or ones of a very seasonal nature, dormancy can only be an adaptive strategy if a stimulus for the seed to move from a « dormant » to a « non-dormant » state is made possible at the « right time ». And indeed, dormancy often does indeed cease when environmental conditions permit.

The longevity of a seed (the length of time it can remain in a dormant state without losing its ability to germinate) is highly variable. In plants, all the intermediaries exist, between the seed of the lotus which holds the record of longevity (about1000 years) and the seeds of cocoa tree, little dehydrated, which must, under pain of death, find, in the few days following their maturation, conditions allowing their germination. Scientists have even managed to germinate seeds of silence (a plant with white flowers) frozen for nearly 32,000 years in the Siberian subsoil! 

Although costly, the dormancy strategy prevents all individuals carrying the same genotype from simultaneously encountering an environment not conducive to their survival or reproduction.

A rotifer survived 24,000 years of freezing in the Arctic permafrost.

Bdelloid rotifers generally live in aquatic environments and have an incredible ability to survive. Russian scientists discovered these creatures in a core of frozen soil extracted from the Siberian permafrost using a drill.

In a study published recently in the journal Current Biology, the Russian researchers used radiocarbon dating to determine that the creatures they recovered from the permafrost (ground that is frozen year-round, except for a thin layer near the surface) were about 24,000 years old.

This is not the first time ancient life has been « revived » from a permanently frozen habitat.

Antarctic moss stems were successfully regenerated from a 1,000-year-old sample and a living campion flower was regenerated from seed tissue, probably stored by an Arctic squirrel, that had been preserved in 32,000-year-old permafrost. Simple worms, called nematodes, were « resurrected » from permafrost at two locations in northeastern Siberia in sediments more than 30,000 years old.


This month’s good news: Private investments for longevity. The European Union announces widespread health data sharing for its citizens by 2025.


  • Vitalik Buterin donates over $2 million to the Methuselah Foundation.
  • Michael Greve, founder of Forever Healthy, pledges 300 million to advance rejuvenation startups.
  • In an unfortunately poorly circulated document, the European Commission announces that it aims to have EU citizens able to share their health data with the healthcare providers and authorities of their choice by 2025. This would mean, if followed through, that European citizens will be able to easily share their data for scientific research, including healthy longevity.

For more information:

The death of death N° 146. May 2021. Regeneration

Thomas Pesquet, the current star of French scientific research: « If we could unlock the key to aging and figure out how to reverse it, that would be super convenient. » (translation)


Theme of the month: Regeneration


All living beings are capable, at different levels, of repairing damage to their organism. 

In biology, regeneration is the capacity of living organisms to rebuild themselves after a natural or accidental destruction of a part of themselves. 

Stem cells: the key to regeneration?

Regeneration can involve cells, organs or functional parts of certain living beings. The ability to regenerate is mainly carried by cells of the body that will reprogram themselves to replace the damaged tissue or organ. Some of these cells called « stem cells » are generated either by the bone marrow and can circulate in the body, or by the tissues themselves.

 Regeneration in humans

The human body is constantly subject to cell death and regeneration. However, this regeneration is not exactly the same depending on the type of organs and cells.

Some cells are completely replaced by new ones in a very short time. For example, the cells of the intestines and stomach are only used for a few days before being evacuated by the body. The skin is completely renewed in a few weeks due to external aggressions. Some cells even live only a few hours, like white blood cells.

On the other hand, some cells are renewed slowly. For example, it takes about ten years for bones to be completely regenerated. Heart muscles regenerate by only 1% each year after the age of 20.

But our body also contains cells that never regenerate! This is the case of oocytes or certain neurons in the cerebral cortex.

We must not confuse regeneration and healing, even if they can be observed together, they are two very distinct phenomena. Healing is only a partial repair of the cells, but does not allow an identical reproduction.

We certainly cannot regrow a leg or an arm, but some animals can regenerate whole parts of their body!

Regeneration in living beings

The regeneration capacities of certain plants, notably trees, are remarkable. But the genetic and physiological functioning is so different from that of animals, and therefore also from that of humans, that there is no prospect of application against human senescence appearing conceivable in the short or medium term.

The ascidian, a curious small marine invertebrate in the shape of a wineskin, has the ability to renew its tissues very quickly after serious injuries. Other invertebrates, such as the flatworm and the planarian, can regenerate their head from a tail fragment and vice versa. These invertebrates are not the only animals with such regenerative powers.

Among vertebrates, too, we can find experts in regeneration. The axolotl, a small amphibian that can regrow its limbs, organs and even parts of its brain. The zebrafish regenerates its heart tissue without needing stem cells. Salamanders regenerate their limbs, heart, tail, eyes, kidneys, brain and spinal cord throughout their lives. 

How do these animals with regenerative abilities manage to regrow such complex structures?

Understanding the regeneration process

After an amputation, stem cells accumulate at the site of injury in a structure called the blastema. A major part of current research focuses on how signals from the injury site indicate to stem cells to form the blastema and begin dividing to rebuild the missing structure. 

But what happens at the level of the stem cells themselves? Do the animals use a single type of blastema stem cell that can differentiate into multiple tissues? Or do different groups of stem cells produce the different tissues required to form the new organ?

Recent research in animals with regenerative abilities has shown that stem cells use a variety of strategies to reconstitute missing body parts from multiple tissues, such as muscle, nerve and skin. 

In this 2014 study, scientists combed through the 23,000 genes of Anolis carolinensis, a lizard about 20 centimeters long. Its complete genetic sequencing had already been completed in 2011. But this time, the study’s researchers scanned all the genes during tail regeneration to isolate those responsible. The result: at least 326 genes are activated in the phenomenon, a real « recipe » in the lizard’s DNA.

Another group of scientific researchers in the United States recently solved the mystery of planarian worm regeneration. They discovered that adult individuals have pluripotent stem cells that can make all types of cells in the animal’s body. 

In addition to stem cells, the regeneration process uses differentiated cells that have stopped dividing and « start » to multiply again to replace lost tissue. This phenomenon is present in zebrafish where a heart muscle cell divides to reconstitute the missing tissue. This regenerative process has also been demonstrated in the heart of young mice, but it quickly disappears as the animal grows.

Future Research and Challenges: Enabling human rejuvenation through regeneration

As adults, humans can regenerate certain organs such as the liver or skin. Unfortunately, many other human tissues do not have this ability. One of the goals of regenerative medicine is to find ways to stimulate tissue regeneration or make replacement tissues. One day, this could be one of the ways to « cure » humans of aging.

In December 2018, the scientist Michael Levin from Tufts University, demonstrated that by changing the electrical pattern between cells in the planarian worm this resulted in activation of cells indicating to the body its shape by guiding regeneration.

How to limit growth to what is useful (avoid cancerous growths)? How to « start », « reactivate » these mechanisms to allow the regeneration of organs that arenot destroyed, but senescent? This research requires a better understanding of the genetic and molecular mechanisms of regeneration. 

Progress in the use of stem cells, gene therapy, and the knowledge of genetic mechanisms linked to regeneration open up considerable perspectives. This could well be one of the avenues studied by the USA in the framework of the initiative announced below.


Good News of the Month: U.S. President Joe Biden Announces Advanced Health Care Agency in First Address to U.S. Congress


« The Department of Defense has an agency called DARPA (Defense Advanced Research Projects Agency), whose mission is to develop advances to strengthen our national security. This agency gave birth to the Internet, GPS and many other things. The National Institutes of Health, NIH, should create a similar agency for advanced research projects in the health field. To develop breakthroughs – to prevent, detect and treat diseases like Alzheimer’s, diabetes and cancer.

This is a personal issue for many of us. I can’t think of a more worthy investment. And I don’t know of anything more bipartisan. Let’s end cancer as we know it. It’s within our power. » (Source)

The DARPA agency specializes in « disruptive » technologies. So this new agency could quickly target « disruptive » research in health and anti-aging.


For more information:

The Death of Death. N° 145. April 2021. Secrets of longevity of blue zones

Levelling up health is important. We want to level up life and you can only level up life by levelling up life expectancy. Matthew Hancock. 1921. British Secretary of State for Health and Social Care (source).


Theme of the month: Secrets of longevity of blue zones 


Worldwide, life expectancy is currently about 71 years. In 2019, life expectancy at birth in Belgium was 81.8 years for the total population, 84.0 years for women and 79.6 years for men.  In some Asian countries (Singapore, South Korea, Japan), it is even higher.

However, this is less than the exceptional longevity observed in specific areas of our planet where there is a large proportion of centenarians. These regions were identified by two demographers, Gianni Pes and Michel Poulain, and the journalist Dan Buettner, author of the article The secrets of Long Life published in the National Geographic magazine and the book The Blue Zones.

The 5 Blue Zones identified in the world

Sardinia, Italy

By studying the longevity of the inhabitants of Sardinia, demographers Pes and Poulain and their collaborators have located areas where more centenarians live. These longevity hotspots or Blue Zones (the researchers initially used a blue marker to delimit these zones on a map) are located in a mountainous region of the island, the Barbagia, which was still difficult to access a few decades ago. Such a geographical situation favors inbreeding, reducing the diversity of the genetic heritage. In the area of exceptional longevity, in the southeast of the province of Nuoro, 91 people became centenarians among the 18,000 people born in the area between 1880 and 1900. In one particular village (Seulo), 20 centenarians were counted between 1996 and 2016. 

Analysis of genes involved in inflammation, cancer and heart disease did not reveal any significant differences that could be related to the exceptional longevity of the Sardinians. The researchers therefore suspect that environmental characteristics, lifestyle and diet are much more important than genetic predispositions for living long and healthy lives. 

Many of these Sardinian centenarians are shepherds or farmers who have done a lot of physical activity outdoors throughout their lives. The Sardinian diet, which is part of the famous Mediterranean diet, could play an important role. It consists of home-grown vegetables (especially beans, tomatoes and eggplant), whole grain bread, pecorino cheese made from whole milk from grass-fed sheep, and local red wine particularly rich in polyphenols. The diet includes meat only once a week at most.

When centenarians are asked about their exceptional longevity, they frequently mention the importance of family and social ties. In Sardinia, the elderly live with family, not in nursing homes. Seniors living in the Sardinian Blue Zone report excellent mental well-being and few symptoms of depression. An Italian study of 160 seniors in this Sardinia Blue Zone reported that the trait of resilience was significantly associated with markers of good mental health. 

Okinawa, Japan

Japan has one of the highest concentrations of centenarians in the world, more than 34.7 per 100,000 inhabitants in 2010. Inhabitants of the Okinawa archipelago in southwestern Japan have a particularly high life expectancy and 66.7 centenarians per 100,000 inhabitants have been counted in this prefecture. Women living in Okinawa are 3 times more likely to live to 100 than North American women. The exceptional longevity in Okinawa is the result of a set of favorable factors that are not limited to genetic heritage. Most of these factors are highly cultural and related to the traditional Okinawan lifestyle.

The Okinawan diet is based on plants, many green leafy vegetables, sweet potatoes, fish and seafood. The majority of Okinawan centenarians have maintained a vegetable garden throughout their lives, moderate physical activity to keep fit and reduce stress. Okinawans traditionally practice self-restriction by following the Confucian-inspired teaching of « hara hachi bun me » which recommends eating so as to be 80% full at the end of a meal. The elderly in Okinawa are very active and maintain strong family and social ties, for example during regular meetings called « moai ». It is very important for them to give meaning to their lives, to have an « ikigai » i.e. to have a reason to get up every morning.

Nicoya, Costa Rica

Life expectancy is relatively high in Costa Rica (82.1 for women and 77.4 for men), but it is especially high in one region of the Nicoya Peninsula where men aged 60 are 7 times more likely to become centenarians than other Costa Ricans. Like Sardinia, Nicoya is a region that has been relatively isolated for hundreds of years. It has a 23% lower death rate from cancer than the rest of the country. Nicoyans eat a plant-based diet (squash, black beans, corn tortillas, lots of local fruits), but also include eggs and meat (chicken and pork). Nicoya centenarians are very physically active, have strong family ties, a strong religious faith and enjoy working. They have very little stress and are generally very positive and happy.

Loma Linda, USA

The only identified Blue Zone in North America is located in Loma Linda, a city in California where there is a community of 9,000 members of the Seventh-day Adventist Church. In California, an Adventist male aged 30 will live an average of 7.3 years longer than a white Californian of the same age. A 30-year-old Adventist woman will live an average of 4.4 years longer than a California woman of the same age. Given that about two-thirds of Americans die from cardiovascular disease and cancer, it is not surprising that Adventists live longer since their lifestyle puts them at less risk for these diseases. About half of Adventists are vegetarians or rarely eat meat and non-vegetarians are twice as likely to develop cardiovascular disease. The majority of Adventists are non-smokers and do not drink alcohol. As a result, they have a lower incidence of lung cancer than Americans in general. Adventists are physically active and have a strong sense of community, as they are very religious and their church encourages members to help each other.

Ikaria, Greece

Icaria is an island in the eastern Aegean Sea where one in three inhabitants reaches the age of 90. The incidence of cancer, cardiovascular disease, diabetes and dementia is significantly lower. As in Sardinia, Okinawa and other Blue Zones, Icarians maintain a vegetable garden at home and lead a low-stress life. The Icarian diet is Mediterranean in style and consists of vegetables (potatoes, peas, lentils, green leafy vegetables), fruit, olive oil, fish, goat’s milk, dairy products and a little meat. Icarians eat little sugar and drink coffee, red wine and herbal teas made from rosemary, sage and oregano on a daily basis. Icarians who observe the Greek Orthodox Church calendar must undergo regular fasts. Caloric restriction is known to slow the aging process in mammals.

Common characteristics of regions where people live better and longer

People in the Blue Zones, Okinawa, Sardinia, Nicoya, Icaria and Loma Linda, share characteristics in their lifestyles that contribute to their longevity. Dan Buettner in his book The Blue Zones lists 9 common characteristics:

  • Moderate, regular physical activity throughout life.
  • Caloric restriction.
  • Semi-vegetarianism, with most of the food coming from plants.
  • Moderate alcohol consumption (especially red wine).
  • To give meaning to one’s life.
  • Reducing stress.
  • Commitment to spirituality or religion.
  • Family is the center of life.
  • Social commitment, integration in the community.

These blue zones have in common that they are sunny and airy areas. They are also relatively isolated, either geographically or according to religious practices (Loma Linda). The diets are different, but they have two aspects in common. The first is that they are based on plant-based foods, with meat, fish or cheese only in small amounts or during holidays, local, fresh, minimally processed foods. The second is that they eat vegetables. As for the flavors, the diets are very different. If the population of Icaria has a diet close to the Cretan diet (vegetables, fish, white meat), the population of the Sardinian mountain villages do not eat fish but meat, including cold cuts.

The study published by Michel Poulain and Gianni Pes identifies the importance of a healthy lifestyle, at high altitude, with physical activity, even over the age of 80, without stress, with close family and social ties. 

A very strong social bond

« Longevity (in these areas) is explained 10% by genes and 90% by lifestyle, » said Dan Buettner, in his book-investigation « Blue zones: Where do we live better and longer? « .

The social link is at the heart of the particular lifestyle of the « blue zones ».  The case of the Nicoya Peninsula in Costa Rica demonstrates this well. In certain homes in this region, it is not uncommon for three or four generations to live together. A study conducted by the German Max-Planck Institute has proven that regular babysitting of grandchildren improves cognitive function, mental and physical health, reduces the risk of developing Alzheimer’s disease and prevents stress. Passing on the knowledge and memories of grandparents to their offspring also helps them exercise their memory. Another example of the importance of social ties is the Seventh-day Adventist community in Loma Linda, California, the fifth largest blue zone in the U.S., dubbed the « longevity oasis”. There, believers live together and work daily for a common good, creating a strong sense of belonging. This sense of belonging goes beyond simply being kind to one another. Faith is a prominent factor. Together, it’s harder to give in to temptation, so a shared struggle creates beneficial social support that helps reduce mortality.

Meals are also an important source of social connection. According to dietician-nutritionist Alexandra Retion: « It is less and less important, but the happiest people are those who share their meals, who spend time with family or friends. It is very important to take the time to eat together and to share good moments. Conviviality is important. « France is rather a good student in this field because in 2010, UNESCO decided to classify the « gastronomic meal of the French » as intangible cultural heritage of humanity. A distinction that recognizes this social practice based on conviviality, the pleasure of taste, sharing, the association with wine, the link to the land, etc.

By way of conclusion

For a long time, humans have sought mythical places of longevity. Sometimes beliefs about longer life are simply due to unreliable records of births and deaths and an exaggeration of longevity. For example, even today, some people believe that the people of Hunza have the secret of living to 145 years.

The blue zones will not allow us to live forever. However, they do teach us that we can still make significant progress in healthy longevity, even without a breakthrough medical discovery. This can save a few years of healthy life, even compared to the longevity of the already most favored countries.


This month’s good news: Insects can also tell us about healthy longevity


We know that the maximum lifespan is genetically fixed. No mouse (Mus musculus) in the world lives more than 4 years, no human being more than 122 years, and no gastrotrich (small marine invertebrate) lives more than a few days. 

However, among social insects, maximum life spans vary considerably depending on the role of the individual. An article in Science details this situation. The most striking example is that of the queen termite, a gigantic « egg-laying machine », which lives up to 20 years, whereas the workers live only two years. The difference in lifespan also concerns the queens of bees and ants. 

The study of arthropods therefore holds out hope. Especially since some of these insects contradict the general principle that small animals have short life expectancy.


For more information:

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:

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 :