)(§These actions will be funded by the EU4 Health (…) and Horizon Europe programmes, with the aim that by 2025 (…) citizens in all Member States will be able to share their health data with healthcare providers and authorities of their choice (…). This extract from a Commission Communication to the European Parliament (Fostering a European approach to artificial intelligence) means, if put into practice, that every citizen will be able to share this data with scientists (with data protection guarantees, of course). This would be a very big step forward for longevity research and for health in general.

Theme of the month: Massive health data and longevity. European developments.

Introduction

Health « Big Data » is everywhere: it seems it represents 30% of the total mass of data available in the world. Today, in a country like France, almost all medical activities are at some point recorded by computer.

The issue of accessibility of health data for researchers has already been addressed in a letter of September 2020. This letter details recent developments, hopes and limitations at the level of the European public.

The hopes

The acceleration of digitalization in health during the pandemic and massive data

First of all, we are already in the era of Medicine 4.0. At the same time, as a result of government measures in the fight against the Covid-19 pandemic, the digitization of health care has accelerated worldwide: the debate about personal data for medical purposes is spreading among the population.

This pandemic has affected us so much and, at the same time, has forced us to think about public and individual health. No responsible decision-maker would want to repeat this physical and moral restriction without a scientific understanding of the causes. Therefore, many will reflect on the importance of sharing « big data » in order to obtain a faster and more efficient measurement of results, for drugs, vaccination or prevention. Finally, Covid-19 was an opportunity to realize the usefulness of sharing massive data in health.

Institutional work in the post-Covid-19 era

In this context, the European Union is taking an initiative to create a common platform between the Member States: the European Commission is considering the creation of a European Data Space including the field of health for the period 2019-2025.

In December 2021 the European Parliament and the Council of the EU announced their agreement on the Data Governance Act (GDA). This agreement aims to facilitate altruistic data practices between public and private organizations to support scientific research.

As for scientific research, a new regulation of the European Parliament and of the Council concerning clinical trials for human use, Regulation No 536-2014, came into force on 31 January 2021. It envisages the creation of a CTIS platform, Clinical Trials Information Systems. This is an optimistic first step towards sharing data for research purposes. It is only the beginning of a project that will bring about change within the European area.

Innovative state systems in the European Union

Regarding the system of sharing massive health data at state level, there are several states in the European Union that have made a platform available. For example, Denmark has had the « Medcom » system for 25 years, and in Sweden the Swedish National Data Service also exists for the re-use of data for research purposes. It is the trend towards the re-use of health data at state level that could influence other Member States.

In this context, the joint TEHDAS project for the re-use of health data brings together 25 European countries. This consortium plans to start in 2022.

The notion of data altruism

In discussions on data management in general (not only health data), some have advocated for the concept of « altruism » for organizations that would be data controllers. The idea is to create a category of organizations that present guarantees of efficient processing on the one hand, and of processing in accordance with the objectives on the other. For example, in the case of health research, this would mean that it would be inaccessible in law and in fact to insurance companies, employers, etc., but accessible to researchers.

The difficulties

The Health Data Hub in France and the RGPD

In France, the temporary failure of the Health Data Hub project (L1462-1 Code de la santé publique) became apparent in December 2021. The government’s withdrawal of its request for authorisation from the CNIL is a consequence of a political strategy before the presidential election in 2022. The choice of a suitable cloud is essential. For the sharing of massive data, this is a big obstacle.

According to the judgment of the Court of Justice of the European Union of 16 July 2020 (the Schrems II judgment), transfers of personal data from the EU are contrary to the RGPD as well as to the Charter of Fundamental Rights of the European Union. Unless there are additional measures or transfers are justified under Article 49 of the GDPR (paragraph 5: « In the absence of an adequacy decision, Union law or the law of a Member State may, on important public interest grounds, expressly set limits on the transfer of specific categories of personal data to a third country or to an international organization. »).

Therefore, the Health Data Hub project has to be postponed as announced to the end of 2021.

The Health Data Hub is also arguably something of a white elephant. Despite the nice plans to share data, the practical situation is that only a few of the hundreds of requests from scientists for access to data are successful.

Fear of influence by US giants

A European cloud project, Gaia-X, was launched in 2019, based on collaboration between France and Germany. It aims to establish an autonomous system in the face of American and Chinese competition. It provides a framework for data exchange. This gives hope, for example, to solve the problem of choosing the cloud for the Health Data Hub, as mentioned above. 

Limited EU intervention in health for Member States

Despite the existence of several programmes and work by the European institutions in the field of health data sharing, the realization of data sharing does not seem to be close. One of the causes of this difficulty is the fact that the shared competence of the European Union in health matters is limited as follows: TFEU Article 168 paragraph 4 a,b,c.

Except in these limited matters, the EU can intervene in a non-binding way even if the data shared are health-related: it is up to the Member State to decide whether to make such a measure available.

The GDPR and the limiting provisions related to privacy

In theory, the famous General Data Protection Regulation does not prevent scientific research. In practice, it is clear, particularly in times of Covid, that there is a kind of mechanism of fear mongering – sometimes not very rational – in particular towards public health authorities. This mechanism leads to a great slowness in authorisation procedures, or even refusals, with many useful research projects being delayed.

Technical difficulties

Beyond the complexities of policy decisions and privacy issues, there is a need to ensure data interoperability. This is complex, especially at the European level, as IT systems and data come from very different sources. ‘Trash in, trash out’ situations, i.e. incorrect (or incompatible) information ‘corrupting’ other data, must be avoided.

In conclusion

There are countless initiatives to share data, especially for scientific purposes.

An ideal solution would be a system:

• Having the trust of the citizens
• Managed by a public institution (or non-profit organization)
• Allowing by default (opt-out) the use of all health-related data (anonymized or pseudonymized) 
• For scientific research (not for other uses).
• Ultimately enabling everyone to live longer and healthier lives.

The European Union is currently the most appropriate place to develop this.

Good news of the month. Major advances in xenotransplantation.

Under normal circumstances, a transplant of a pig heart or kidney into a human body leads to immediate rejection, sometimes even before the operation is completed. For the first time, these two operations have been performed on two patients. This is very promising. For more than a month, David Bennett has been living with the heart of a pig and since September 2021 another patient has been living with the kidney of a pig. To make this possible, the animals were genetically modified. This means considerable progress for gene therapy as well as for xenotransplantation. And so in what may be a short time, it is very useful for research into healthy longevity.

For more information:

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

The law is 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 significantly reduces life span, accelerating all diseases. While smoking causes cancer, rapamycin prevents it, including smoke-induced lung cancer. Is it not paradoxical, then, that alcohol and tobacco are sold without prescription, while rapamycin and metformin are not? The Goal of Geroscience is Life Extension. Mikhail V. Blagosklonny February 2021. (Translation)

Theme of the month: Sarcopenia and Longevity

What is sarcopenia?

With advancing age, almost everything that makes up the components of a human being or other vertebrate gradually loses its efficiency: digestive, cardiac, neurological and immune systems, skeleton, skin, etc. Muscles are no exception to the rule.

Sarcopenia (or age-related muscular dystrophy) is the age-related progressive decline in muscle mass and strength, associated with a decline in physical performance.

In 1989, the term « sarcopenia » was defined by Irwin Rosenberg, researcher and acting director of the Neuroscience and Aging Laboratory at Tufts University in the United States, to refer to the decrease in muscle mass during aging.

From what age?

From the age of 30, muscle tissue undergoes a progressive degeneration of about 3 to 8% per decade. From the age of 50 onwards, the loss of muscle quantity and strength accelerates. By the age of 70, half of the muscle mass is lost to fatty tissue. The loss of muscle mass affects all older people, including those who are healthy and active.

The causes and consequences of sarcopenia?

Several interrelated causes are involved in the development and progression of sarcopenia. These contribute to the loss of muscle mass and strength:

• Denervation and loss of motor unit functionality is thought to result in reduced muscle fiber constructibility.
• The effect of anabolic hormones is strongly disrupted in the course of aging. Either the concentration of circulating hormones is reduced, or the sensitivity of the muscle to the action of certain hormones such as insulin appears to be diminished.
• Dietary proteins are no longer used efficiently by the body. As a result, the nutritional intake of the usual diet is inadequate to meet the needs of the aging body.

The risks and consequences of sarcopenia vary greatly depending on age and degree of impairment:

• Progressive decrease in muscle strength
• Fatigue leading to a decrease in physical activity
• Weakness
• Increased risk of falls and fractures
• Increased risk of dependency and loss of quality of life.

Is it possible to slow down sarcopenia?

Some nutritional strategies combined with sufficient physical activity make this possible.

Protein pulse feeding: « this consists of providing 80% of the recommended daily protein intake in a single meal. This technique makes it possible to partially saturate splanchnic extraction (i.e. retention of dietary amino acids by the intestine and the liver for their own needs) in order to obtain better bioavailability of amino acids for the stimulation of postprandial muscle protein synthesis » (source: Wikipedia).

Citrulline (the only amino acid not taken up by the liver) and leucine both have a stimulating effect on muscle protein synthesis through their action on the mTor pathway. They are therefore good strategies for combating sarcopenia.

In addition, in order to reduce muscle loss as well as for the proper functioning of the rest of the metabolism, sufficient physical activity must be combined with the nutritional strategy.

What is the state of scientific research on sarcopenia?

In December 2021 laboratory-grown human muscle cells were launched into space in an experiment conducted by the University of Liverpool.

This study, called MicroAge, aims to monitor the growth of muscle cells in microgravity and help understand why the body weakens with age.

At the end of the experiment in January 2022, the muscles will be frozen and returned to Earth where scientists will undertake further analysis.

The relationship between sarcopenia and cardiovascular disease 

Both sarcopenia and cardiovascular disease are accelerated by the chronic inflammation of aging, but the onset of physical weakness resulting from sarcopenia can also contribute to cardiovascular disease through reduced physical activity.

Changes in lean body mass are common critical determinants in the pathophysiology and progression of cardiovascular disease (CVD). Sarcopenia can induce CVD through common pathogenic pathways such as malnutrition, physical inactivity, insulin resistance and inflammation; these mechanisms interact. 

Sarcopenia and CVD are widespread in the elderly and share common pathogenesis and interactions. The understanding of their relationship is still in its infancy, and more clinical and experimental data are needed. 

A large number of studies have shown that the progression of CVD and the decline in muscle function worsens the condition of patients. By screening for sarcopenia at an early stage, with effective detection and assessment methods in place, it is possible to effectively delay the progression of the disease.

Sarcopenia and gene therapy

In 2015, Elizabeth Parrish underwent a – controversial – gene therapy with telomerase and follistatin as part of the creation of the startup BioViva. In the case of follistatin, the aim is to directly suppress myostatin or to enhance follistatin to suppress myostatin. This has the effect of increasing muscle mass and reducing fatty tissue, while adapting the functioning of the metabolism to a healthier mode of functioning.

These injections consist of a myostatin inhibitor to protect against the loss of muscle mass with age.

After further examination and testing, comparison of Parrish’s pre-therapy and post-therapy data revealed additional positive changes.

And tomorrow?

As written at the beginning of this letter, with age, almost everything that constitutes the organic components of a human being or any other vertebrate gradually loses its efficiency. But the rate of loss varies greatly depending on the tissue: from 1 to 1000, from a few weeks to a few centuries. The future, thanks to the progress of knowledge already underway, may consist in doing at least as well, sustainably and … muscularly as the longest-lived species.

Good news of the month

The World Health Organisation (WHO) maintains the International Classification of Diseases (ICD), which is revised regularly. 

ICD-11 officially came into effect on 1ᵉʳ January 2022 (although implementation of ICD-11 may not begin for several years.

Unlike previous versions, ICD-11 allows for a variety of synonymic interpretations, including those that may be very useful to a clinician treating older people, such as « aging », « senescence », « senile state », « frailty » and « senile dysfunction », which refer to a health condition. The new classification includes the code « age-related » in the etiology or causality category to target the pathogenic processes of aging.

Some have suggested that the code « old age » should be excluded from the latest version of the International Classification of Diseases, ICD-11, on the grounds that treating old age as a disease could have the negative consequence of treating civil age as a disease.

Yet, far from discriminating against the rights of older people and encouraging neglect of their curative or preventive health care, the ICD-11 codes for old age and age-related causation do exactly the opposite: they draw public and professional attention to the specific health problems of older people and call for action to improve prevention and treatment specific to them.

For more information:

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

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Imagine a rather educated mouse asking himself if it is theoretically possible to live more than two and a half years his average life expectancy? Of course, it is possible, she would say, look at the human species (…), mammals like us that live thirty to forty times longer! Beyond our biological limits: The secrets of longevity. 2011. Miroslav Radman.

Theme of the month: If humans didn’t die of old age, would we regret it?

Introduction
Let’s imagine a world not so different from ours. However, humans and most animals would not experience aging.

In this world, would we wish senescence, that is, the progressive degradation until death, on ourselves and our children?

Let’s imagine, for example, a biological environment a little more « Lamarckian » than the one we live in. In epigenetic evolutions, acquired characteristics would be more transmissible. An older animal would have, as here, advantages in terms of experience. Moreover, the descendants would benefit from an increased transmission of acquired characteristics. In this case, natural selection would have less « need » for senescence, since the evolution of species could occur because of changes during the life of individuals. Let us imagine that the probability of dying of natural causes is therefore relatively stable, from one year to the next, once the adult age is reached. Let’s imagine a planet with no aging death (and also no aging degradation) for most living species.

For the rest, the « laws of nature » would apply: selection of the most adapted, evolution of preys, predators and parasites, competition and cooperation between animals, plants, bacteria, fungi… Animals would live longer, without aging, but would still die from all other causes. Biological immortality is not the same as immortality.

A world without aging would not be paradisaical but…
Obviously, it is impossible to imagine all the consequences. Let’s focus on humans. Theoretically, some could live for thousands of years. But this would be extremely rare before the development of civilizations because epidemics, predation, violence would strike all individuals.

But once civilizations appeared, the environment would be radically different. The accumulation of knowledge would be faster, philosophers, scientists, leaders could be influential for centuries. Religions would exist, but they would logically be more peaceful, less focused on the afterlife, more concerned with bodies and souls here than with the afterlife.

Soon enough, in the more prosperous regions, birth control would expand. Soon enough, science and medicine could focus more on preventable causes of death. Indeed, the positive stakes of disease control would be higher, there would be more years of life to gain.

As for these humans, the capacities would not decrease with age, the mechanisms of nostalgia, of withdrawal to the past, would be less. Indeed, nostalgia is often the regret of youth following the loss of energy, health, taste, other senses… Nostalgia following the loss of loved ones would also diminish. 

In our contemporary world, philosophy is sometimes defined as « learning to die » (and to die quickly). Where death would no longer be inevitable, at least on the scale of centuries, philosophy would be more about learning to live, learning to respect others and oneself. In a more stable world, the need for an environmental balance is more obvious.

Advancing age would be, as in our world, synonymous with wisdom. It would be a wisdom with less bitterness and regret of the past and therefore more openness to the future.

In this place where death is no longer inevitable and is becoming rare thanks to technological and medical progress, it is possible to imagine that any death inflicted, any murder, would not only be unacceptable, it would become unimaginable. Just as today killing a child is almost unimaginable, because he has « his whole life ahead of him », whereas in the past infanticide was often tolerated and sometimes totally accepted, especially because many children died in infancy.

In a world without age-related degradation, would we invent aging?
Some philosophers, some religious leaders might want the older ones to disappear. Some might say that it is necessary to renew the population, to have children without the risk of overpopulation.

Would the representatives of this current of thought want to kill the most advanced people in age? And if so, create a system where death is slow, insidious, progressive, painful, ineluctable… rather than, for example, creating compulsory euthanasia for some?

This seems unlikely in a world of less violence. Already today, even the most bloodthirsty regimes no longer (almost?) officially practice torture as a means of pressure. So inflicting aging and then death …

What if the glass was half full?
Let’s finally imagine an environment where humans are not amortal, but live twice as long once they are adults. The prime of life would be at 100 years and Jeanne Calment would have lived 245 years.

No one would likely propose ending life after 80 or 90. It is the situation well beyond that which would be « normal » and would appear to almost everyone as desirable… until the situation changes.

Just as no one today proposes to end life at age 50, when that was the « normal » maximum lifespan for most of human history.

Conclusion
If aging did not exist, we would not have to invent it. All other things being equal, we probably wouldn’t consider it, even for our worst enemy. We would not wish for years and sometimes decades of unbearable degradation ending in death.

Moreover, if we lived in a world without aging, not only human life, but also the lives of sentient beings (capable of suffering) would be far more precious. Even the most disrespectful of individuals, raised in this universe, would have difficulty imagining inflicting the torments of an endless torture called aging. Just as today, even a violent recidivist thief would probably not think of burning the feet of an elderly person to make him confess where his money is, and then murdering him, a common practice in France and elsewhere until the early 19ᵉ century.

Aging is now inevitable. We have already managed to humanize it considerably. We are also managing to slow it down a bit. Tomorrow we may be able to stop it. In all likelihood, we will not regret it any more than we regret the eradication of the plague and cholera.

Good news of the month

• Japanese scientists develop a vaccine to eliminate cells responsible for aging. The team, including Toru Minamino, a professor at Juntendo University, confirmed that mice given the vaccine had a decrease in the number of zombie cells, known medically as senescent cells. The team identified a protein found in senescent cells in humans and mice and created a peptide vaccine based on an amino acid that constitutes the protein. This news has received significant media coverage. It is part of the many hopes for senolytic products. However, the experiment concerns only mice. Moreover, the maximum life expectancy was verified on « progeroid » mice (with a much shorter life span), but not on « normal » mice.
• The first clinical trial of a nasal vaccine for Alzheimer’s disease began in Boston. The vaccine, formulated from an immune-boosting substance (Protollin), is intended to prevent and slow the progression of Alzheimer’s disease, the disease associated with aging for which medical research has been slowest… A Phase 1 trial involves 16 participants, aged 60 to 85, all with early-stage Alzheimer’s disease but in good general health. They will receive two doses of the vaccine. The research team will measure the effect of nasal Protollin on the immune response, particularly its effect on white blood cells, by examining cell surface markers, genetic profiles and functional tests.

For more information:

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

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John Harris, former editor of the Journal of Medical Ethics, argues that as long as life is worth living, according to the individual, we have a powerful moral imperative to save life and therefore to develop and offer life-prolonging therapies to those who want them (Source). 

Theme of the month: Recent developments in gene therapies for longevity

Introduction 

The average lifespan of both animals and humans varies according to many factors. For animals,  diet, predation, disease and  climatic conditions play the most important roles. In humans, lifestyle, disease and social conditions are the determining factors.

But when it comes to the maximum lifespan of animals, like that of humans, the most important element is the genetic heritage. 

We still know very little about the genetic differences that favour or hinder longevity in humans. Studies of genetic characteristics related to longevity have been conducted, including studies of supercentenarians.  Although genes such as the klotho gene are sometimes cited, no single gene or group of genes appears to have a very strong positive influence.

A human being who lives in a perfect environment with adequate health care and an exemplary lifestyle would never live past the age of 122. It should be noted that the oldest person in the world has been a woman for almost 40 years, which can be explained by the genetic difference between men and women. 

Place a mouse in a mouse paradise. No matter what happens, it won’t live past five years. Place a Galapagos tortoise in a chelonian paradise and it will live at most two centuries.

Very similar animals can have very different maximum life spans. For example, the Labord’s chameleon of Madagascar is the terrestrial vertebrate with the shortest life span. It lives only 4 or 5 months. While its distant cousin from the same big island, Parson’s Chameleon, can live for about ten years.

In other words, we know that few genetic modifications can allow considerable changes in lifespan.

This is one of the reasons why gene therapies are among the most promising therapies for longevity.

What is gene therapy? 

Gene therapy is one of the preferred ways to treat genetic diseases, but also certain cancers. It consists of inserting into the patient’s cells a normal version of a gene that does not work and causes the disease. 

The functional gene then allows the patient to produce again the protein whose deficiency was the source of the disease.

However, three conditions must be met: 

• Knowing the gene responsible for the disease, i.e. the function of that gene, so that the cell can be « repaired ».
• Allowing the gene to reach and enter the cell with the help of a « vector », most often a virus that has been rendered harmless to the patient.
• And associate the gene with a « promoter », a small DNA sequence that allows it to function once inside the cell.

It is also possible to transform the genetic heritage of subsequent generations. It is conceivable that one day our children could live longer and healthier lives as a result of genetic modification. This raises innumerable ethical questions, some of which have been addressed by the birth of two (or perhaps three) genetically modified babies in China. These issues will not be discussed here.

The gene therapy revolution

In 2000, for the first time in the world, gene therapy demonstrated its effectiveness with bubble babies, children with severe immune deficiency who returned to normal life with the treatment. However, the therapies were slowed down and then virtually halted for more than a decade following the deaths of two patients, including Jesse Gelsinger. However, during this interruption countless lives could have been saved.

Between 2015 and 2020, gene therapy has experienced a considerable boom. Several clinical trials have been conducted to treat certain blood, skin and neuromuscular diseases. Some of these trials have been sufficiently successful to lead to market authorization in the United States and Europe. 

In 2017, a team of European doctors managed to replace 80% of a little boy’s epidermis (suffering from epidermolysis bullosa) with gene therapy.

By 2019, about ten gene therapy treatments for rare blood, vision, muscle and certain cancers had received marketing approval in the United States or Europe.

In the same year, the first gene therapy drug (Zolgensma) capable of saving the lives of babies with diseases such as spinal muscular atrophy was put on the US market. 

Other treatments for Pompe disease, adenosine deaminase deficiency, beta-thalassemia, acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and Leber’s amaurosis have been developed.

However, treatments are still usually aimed at uncommon diseases, generally linked to an « error » in a single gene.

Gene therapy and longevity: Can it delay or reverse age-related diseases including neurodegenerative diseases?

In 2019, a study by George Church and his teams showed favorable results of a therapy acting simultaneously on three genes in mice with various age-related symptoms.

In the same year, an experiment on a gene for telomeres was carried out by researchers from the Chinese Academy of Sciences on mice in 2019. This resulted in a longer life expectancy.

In 2020, mRNA vaccines were used to induce immunity against COVID-19. This method is similar to gene therapy. However, the changes concern the RNA and not the DNA. 

In October 2021, BioViva, a biotechnology startup led by E. Parrish, demonstrated that by administering gene therapy to six patients with dementia that a reversal of dementia symptoms such as cognitive impairment could be observed. 

The American Elizabeth Parrish is also the first known case of self-testing of a gene therapy targeting ageing processes. The treatment consists of injections of adenovirus, which could extend leukocyte telomeres and thus strengthen muscle mass.

Conclusion

A massive sharing of knowledge, including statistics, about genetic endowments is developing. Investments for a longer healthy life seem to accelerate and improve. The European Union is proposing legislative tools for « altruistic » databases. 

Billions of sequencings (total or partial) have been performed on animals, plants and humans. The pooling of these data and their analysis, in particular by means of tools based on artificial intelligence, is continuing. Thanks to genetic modification technologies such as CRISPR, it should be possible to break through the « glass ceiling » of the maximum lifespan for mice and then for humans in the near future.

The good news of the month

The European Longevity Initiative was launched by a non-governmental organization with members in some 20 EU countries.

Its proposal was the most supported of the Conference on the Future of Europe and is still one of the most supported.

The main promoter of the idea is the Hungarian scientist Attila Csordas, who said:  » The only real solution (for many, many diseases) is to start treating the root causes of biological aging (…). We have experimental strategies to slow down the rate of accelerated aging and reduce morbidity and mortality in late life. To achieve this in the European Union, we would like to propose effective legal, budgetary, regulatory and institutional commitments to enable science-intensive healthy longevity research and technologies, large-scale geroprotective clinical trials focused on ageing and equitable access to these technologies to increase healthy life expectancy in the European Union.”  

The European Health Data Space is at the centre of many projects aimed at better exchange of health data for medical and research purposes. An international conference on 19 November on « Innovations in Consumer Longevity Data » is one example. 

For more information:

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

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:

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

« 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:

• See the following sites: heales.org, sens.org, longevityalliance.org and longecity.org.
• Source of the image. 

« 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: 

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