All posts by didiercoeurnelle

The Death of Death

Copyright and longevity. The Death of Death. July 2019. Number 124.

There are people who think that without the prospect of death, life somehow becomes meaningless. But you know, I look at young children. They are full of joy of life. They bounce out of bed in the morning; they want to get together and play games. They’re not doing that because they think that in the future they’re going to die. They’re living for the sake of life. They’re not living for the sake of death. And it’s my view, we’re quite capable of finding lots of purpose in life, even if there is no threat of death ahead. David Wood, author of The abolition of aging. On the  Skynews channel. June 19, 2019.

Theme of the month: A copyright for the immortality pill?

Introduction

About 26 centuries ago, the inhabitants of Sybaris, a Greek colony in what is now Calabria, invented copyright.

Sybarites were known for their taste for luxury in all respects, including food. They granted cooks the exclusive right to their recipes. According to Phylarchus of Naucratis, an Egyptian Greek from the 2nd century BC: « If a cook invented new and succulent recipes, no other of his fellow chefs was allowed to put them into practice for a year, he alone having the privilege of freely preparing his dish. The stated aim was to encourage other cooks to compete in creating ever more refined dishes.

In 2019, the legal fictions that are intellectual property rights invaded the world’s social life, becoming mixed up in the most improbable areas of our activities: arts, writings, lyrics, dances, inventions, performances and even much of what is natural but theoretically appropriable from certain living species to extra-terrestrial objects. The following are notably « appropriable »: medicines, medical techniques, scientific articles on research for a longer and healthier life, product names….

All this is part of a framework in which signs, symbols and virtual objects occupy an increasingly important place in social life. The resulting complexity, volatility and contradictions generate an increasingly slow decision-making process, a process that unfortunately takes little account of longevity objectives derived from research for health and a better environment.

The ancient Greeks would probably be surprised to find that despite all the imagination of those who profess to monetize any production of the mind, cooking recipes are  generally considered today to be non-appropriable. A diet recipe, a variant of the Cretan diet, presumed useful for longevity, will not be protectable.

But he would be even more surprised to know that if a 20-year-old girl writes a beautiful text for health promotion today and publishes it in what is now France, theoretically, her text will be able to financially benefit her descendants (but practically her publisher) until the middle of the 22nd century, precisely until the year 2159 if the person dies at age 90. Even in a century, in theory, they will be able to refuse to have it published in a way that they consider having a purpose contrary to the author’s ideas. And if research for longevity one day allows a life of unlimited duration, copyright will no longer have a limit (unless there is a change in legislation, of course).

Intellectual property rights – Copyright – Trademarks – Patents

 Here is a very brief summary of a field that spans millions of pages.

Intellectual Property (IP) is the set of rights that allow people to restrict the right of others to use certain things, creations, works on the basis of intellectual « property ». In theory, these rights protect the creator. In practice, these rights almost always protect the creator’s representatives, most often without the creator him or herself gaining anything and having any real choice about the contract. For example, a scientific publishing house or a rights management company may prevent an author from putting his or her knowledge at the service of the community, a company that has bought medical patents can prevent the inventor of a new medical technology from making it available to those who need it…

Copyright is the most classic intellectual property right. A scientific or popular medical article, on paper or online, but also most other forms of original cultural expression such as a photo, a medical plan, relaxing music, an original anatomical sculpture… will in principle always be subject to copyright protection.

The specific word « copyright » is the term used in English-speaking legal systems, notably in the United States and Great Britain, but the concept is more or less the same everywhere. In the « Anglo-Saxon’ countries » legal systems it affects most of the prestigious medical and scientific journals (The Lancet, Elsevier, Springer, Nature…). Generally, copyright, in English-speaking countries and elsewhere, does not expire until 70 years after the author’s death (50 years in certain countries). Today, this right is no longer subject to any formalities, the famous © sign being generally no longer an obligation.

Trademarks benefit from protection that extends to sometimes absurd areas such as common objects (even an apple or windows !). In the medical field, one of the harmful effects arising from this right is that many similar medicines have variable names in order to be able to sell more, which makes them less accessible (due to lack of transparency, confusion about the names of medicines, different pricing, etc.).

A patent is an intellectual right related to an invention. It allows the right holder to benefit from an exclusive right to the economic rights resulting from its exploitation. The right is much shorter than copyright (20 years, sometimes extendable by 5 years) and requires a formality, namely registration. Drugs and medical devices are generally patented.

The consequences of copyright for medicines and therapies

To the question « What can be used for medical progress without fear of legal recourse? », the short answer is « Almost nothing ». Indeed, some people specialize in legal action (on the basis of all commercial law, not just copyright) against any innovative use or more precisely try to obtain profit from any innovative use. Some of these approaches would be comical if they were not particularly harmful to the community. For example, pharmaceutical companies have tried to seize products that have been used by indigenous peoples for centuries. Very often, for copyright reasons but also for tax reasons, these appropriations are attempted by entities with legal status such as « start-ups » and/or with a highly opaque international dimension. Finally, the legal aspects contribute, in an already extremely cumbersome administrative context, to an environment of often surreal complexity generating millions of forms of non-disclosure agreements (NDAs), author’s contracts and other provisions whose implications are not fully understood by anyone, not even the lawyers and other legal professionals who write them.

More broadly, another development may be an overall modification of researchers’ wishes based on the lure of profit but also on the search for respectability resulting from agreements with private companies. Without a start-up, some researchers may (wrongly) think they are nothing. And yet the original goal, for the researchers, is often to bring benefits to the community.

The most well-known negative consequence is the growth of prices to inaccessible levels for some therapies because companies have to generate profits. This concerns the treatment of so-called orphan diseases and also many innovative therapies. Many poor patients die as a result. And where the healthcare system allows for public funding, the costs to the state are high.

 In addition, for products to sell well, it is important to present results in the most positive way and to minimize negative results, which hinders transparency.

 When a pharmaceutical product becomes royalty-free, companies that had patents will feel obliged to conduct research aimed at slightly improving the product much more for commercial than therapeutic purposes. And above all, with regard to progress that is « hard to appropriate, sell or patent », research will be very difficult to achieve by private companies. This is the case for promising research on metformin (whose patent has expired) in the fight against aging.

Generally, DNA and therefore all genetic modifications, particularly in humans, are (fortunately) considered unpatentable. On the other hand, the means to achieve genetic modification are not. A complex legal confrontation exists between the different researchers (and especially the companies!) involved in CRISPR-type research. If, one day, gene therapy is discovered that has an impact on a much longer healthy life, making it accessible to all should be easier legally than photocopying a Tintin cartoon album for your little cousin. 

Consequences of copyright for publications

The publication system for scientific articles is widely recognized as aberrant. A few private publishers have a de facto monopoly on publishing prestigious scientific journals accessible online. Access to these journals is extremely expensive and is therefore in principle almost inaccessible, not only for ordinary citizens, but even for researchers except in « rich » universities. Fortunately, in recent years, considerable progress has been made with the following developments:

 Many publications are published without the consent of the publishers in order to make them accessible to researchers. The best known and most effective initiative is Sci-Hub created by Kazakh computer scientist Alexandra Elbakyan. These approaches are generally considered illegal, even it may sometimes be considered that necessity is its own legal argument in order to allow research that saves lives. In practice, there are many other ways to obtain documents, for example by requesting access from those involved.

 At European level, the S Plan aims to require that from 2021 onwards all publicly-funded scientific publications be published in open-access journals. This plan is part of a logic that should be obvious: what is paid for with public funds must be made available to the public. It is quite surprising to note that the most « progressive » regulation in this area is the  American federal legislation which provides that that which is done by the federal administration is in principle accessible to everyone: from photos of the earth by NASA to documents useful for medical research.

Conclusion and prospects

Despite the gloomy picture above, copyright has certainly had some utility for medical research in the current social and economic environment. Without it, many researchers would no longer have income and much research for products that could be useful for longevity would have to be abandoned.

But a radically facilitated pooling of projects and research results through investment, particularly public investment, would be a considerable factor in progress. It would be useful to have simple and comprehensible legal provisions ensuring that research results are « copyright free » and that the fair compensation of researchers and private partners should in no way hinder the provision of therapies to citizens.

This month’s good news: CHAI, California Initiative on Healthy Aging for a referendum in the Silicon Valley area

Longevist activists in California and elsewhere are supporting an election initiative to provide $12 billion in public funding for research on aging over the next 12 years. California is one of the states where citizens can create laws directly through their votes. In 2004, this process was successfully used to allocate $3 billion to stem cell research. But collecting signatures and educating the public is a costly proposition. They will need a broad coalition of interests (probably with hundreds of thousands of citizens’ signatures) to allow the referendum to take place.

 This is a considerable challenge. If the referendum were to be held, it would be the first time that millions of voters would be directly asked to vote on research for longevity. And what better place to address these issues than Silicon Valley?

For more information:

 

The Death of Death

Epigenetics and aging. The death of death. June 2019. Number 123.

 Pessimism is about selling; optimism is about fighting. (…) If you look at life expectancy, you see that, around the 1850s, it was 30 years for women. Thirty years! Today, it is 85. She’s not the same woman anymore. It’s not the same body anymore. Michel Serres. Philosopher and science historian. Le Soir Monday, June 3, 2019, quoted following his death.

Theme of the month: The epigenetic clock, a marker of aging 

A brief introduction to epigenetics

For a long time, biologists used to say that our body was made up of billions of cells, all different but all with the same genetic code. This was of course DNA, a molecule in the shape of a very long ribbon wrapped in a complex way in 23 pairs of chromosomes and which “unfolded » would be two meters long. In the traditional view, everything was at stake at the time of conception. After this, the cells divided very many times and became specialized, but keeping the same code, the same DNA. In principle, therefore, nothing changed before the creation of reproductive cells.

But this understanding of the fundamental code of living things has been refined. We now know that from time to time, the DNA of the cells that make up our body changes either spontaneously or under the impact of external circumstances and that even identical twins (monozygotic) do not have exactly the same genetic heritage. As we advance in age and when external circumstances are unfavorable, these changes are more and more significant. Cells have means of repairing damaged DNA, but the ability to repair appears to be reduced for people in poor health.

To this already very complex vision, we must add the dimension of a phenomenon that was still almost unknown twenty years ago: epigenetics (from the Greek « epí », « above »). This refers to mechanisms that modify gene expression without changing the nucleic acid sequence (DNA).

It is epigenetics that makes it possible to explain in particular that, while all the cells of a multicellular organism have (almost) the same genetic heritage, they develop in a totally different way according to the category of cells to which they belong, so that a skin cell « knows » that it must not develop as a heart cell.

So what exactly are epigenetic modifications?

Epigenetics is not about the transformation of DNA as such (which is the genetic code), but rather it is about changes that also take place in the cell nucleus and are closely linked to DNA. Some of these changes acquired during life can be passed on to subsequent generations, for example as a result of trauma, contrary to the principle, that was previously thought to be hard and fast, that only DNA determines how the offspring will be.

Epigenetic alterations include three mechanisms called DNA methylation, histone modifications and chromatin remodeling.

DNA methylation conditions the expression of genes in each cell. Nucleotide bases can be modified by the addition of a methyl group. This DNA modification is carried out by specific enzymes called DNMTs (for « DNA methyl-transferase »).

Histones are proteins that allow DNA to become compacted. Through this mechanism, DNA is wrapped around the histones like wire around a coil.

Chromatin is the material composed in particular of RNA and proteins in which DNA is parceled up and compacted, a little, here again, like a ball of yarn, but much more complex. The most « parceled up » parts have the least contact with the outside and the genes located there express themselves less or not at all. Chromatin remodeling, is the modification of this « packaging ».

The above is highly simplified. It is fascinating and vertiginous to think that each of the tens of thousands of billions of cell nuclei in our body constitutes a small universe. Each central element of the basic unit of our body, therefore, contains not only almost everything necessary for the creation of a human being, but also components organizing the expression of genetic heritage, subtle and yet indispensable differences and countless mechanisms that we still only very partially understand.

Epigenetics and measuring aging

Just as it is now getting easier and easier to decipher DNA code including differences between different cells (e.g. genetic characteristics of cancer cells), it is also easier and easier to measure differences in epigenetic components.

These components vary with the passage of time, which is why the expression epigenetic clock is used.

But if the variations of the components were only proportional to chronological age, measuring the results of this clock would not be of interest for the calculation of aging.

In fact, it turned out that the speed with which the clock advances was strongly correlated with other aging mechanisms. An aged person (or indeed an aged mouse) in poorer health will have more epigenetic changes.

It, therefore, seems possible, simply by examining at regular intervals the number of epigenetic changes in a human being’s cells, to get an idea of the speed of his or her aging.

More specifically, since epigenetic modifications are multiple mechanisms, there are many components that can be measured. These include those measured by California professor Steve Horwath and those measured by another American scientist Gregory Hannum.

As in many areas related to the causes and consequences of senescence, there is no consensus as to whether epigenetic changes are first and foremost a cause or a consequence of aging. According to some gerontologists, epigenetic changes can be considered as the engine of growth and of the development of the body and aging as a continuation of the epigenetic program. The epigenetic clock, a good predictor of causes of death, would therefore not only be one biomarker among others, but it would also be an important cause of aging, if not the most important.

A scientist from the East Coast of the United States, Josh Mitteldorf, has the ambitious project to measure thousands of epigenetic profiles of volunteer citizens undergoing anti-aging treatments of all kinds in all parts of the world over a two-year period. This project is specifically designed to look for combinations that work well together, that interact in a highly positive way. In two years, provided Josh finds funding, we could have a global vision of the effectiveness of hundreds of anti-aging treatments.

This would be immensely useful, to limit research in directions that prove to be ineffective and above all to intensify research into what works to enable millions of citizens advancing in age to take adequate preventive and curative treatment.

The good news of the month: French public project for longevity

A project called ExtenSanté is currently being examined in France by citizens, decision-makers, and scientists to promote research and treatments to combat age-related diseases. The campaign already underway includes a text explaining the approach (let’s work on causes rather than consequences), background information provided by different groups, and posters.

For more information:

Image source in.wikipedia.org/wiki/Epigenetics#/media/File:Nucleosome_1KX5_2.png. DNA associated with histone proteins to form chromatin

The Death of Death

The Tithonus error The Death of Death. May 2019. Number 122. 

Human lifespan could soon pass 100 years thanks to medical tech, says BofA (Bank of America). Title of an article from the American television channel CNBC of May 8, 2019. The second largest bank in the United States also estimates that this will open a financial market of at least $600 billion by 2025.

Theme of the month: The myth of Tithonus.

In Greek mythology, Tithonus is a prince, a human being of great beauty. He is so beautiful that Eos, the goddess of the dawn, abducts him and conceives two sons with him. Eos is a goddess, with endless life, while Tithonus must age and die like a human.

Wishing to keep Tithonus forever, Eos asks Zeus for immortality for her lover. Zeus grants it to him, but deliberately omits or forgets (the versions differ) to grant him eternal youth. Tithonus will then live not an eternal superhuman life, but an endless aging and withering.

The idea that a much longer life is not a benefit, but a curse is often expressed by opponents of medical progress. This is one of the many variations of beliefs according to which visible progress must necessarily have as a « counterweight » disadvantages at least as significant as the advantages. In the Greek tradition, still very much present at the heart of Western thought, this illustrates the idea that obtaining that which is not part of the human condition, but of the gods’ – hubris – is a sin of excess which can be punished with the most severe of sentences.

A longer life, but in poor health: myths and realities

In the natural world, generally speaking, the living beings that live the longest are not the most fragile and decrepit. Whether it is whales, redwoods or bird species such as albatrosses and parrots that can live much longer than most other living things, the healthy lifespan is long.

As far as human beings are concerned, it is certain that the last years of life are generally lived in a poorer state of health than the rest of life. But with the progress in longevity, is this situation getting worse?

Firstly, the longer life is, the later the last years of life in poor health occur and the less they represent a significant part of the total lifespan. The last 3 years of a 90-year life are about 3% of the lifespan. The last 3 years of a 60-year life are about 5% of the lifespan.

Secondly, many of the debilitating diseases and conditions of the past have become rare or almost non-existent today. In the US, France, Belgium and Canada, we hardly see any old people with rheumatism, forced to walk with a cane or bent almost 90 degrees. Men and women no longer die slowly from tuberculosis dragging themselves from one sanatorium to another. The typhoid fever from which we died or which made us idiots as 19th century French president Patrice de Mac Mahon would have said, hardly ever strikes anymore. In general, infectious diseases hardly ever cause disabilities anymore and diseases affecting the cardiovascular or respiratory system as well as well-treated cancers allow a life under better conditions than before.

However, there is one area where increases in life expectancy in poor health are significant, namely neurodegenerative diseases, particularly Alzheimer’s disease. Research and healthcare today only help to slow the disease down a little. As the social and healthcare environment improves, affected women and men are living longer, but not healthier lives than before.

Some reasons for the beliefs in an aging process in necessarily poorer and poorer health

The concept of Quality-adjusted life-year is a fairly subjective one. We are much more demanding today than in the past when it comes to health. In addition, we often tend to imagine « good old days » that never existed. On the other hand we often imagine that technological advances are more harmful than they are (consider how much our ancestors were afraid of electricity or of the first locomotives). All this is positive because we are more attentive to good health than before, but it leads to overestimating the time of life in poor health today compared to the past.

More generally, as today we have no choice, as we cannot interrupt the mechanism that leads to death from aging, it is less difficult psychologically to think that not dying would be worse, that we would suffer « a thousand deaths » from it. We are like the fox in Aesop’s fable who tries to grab beautiful grapes and, when he can’t, says to himself « these grapes must be sour ».

Until now, for humans (and also for laboratory animals such as mice), it has been impossible to separate, except very temporarily, advanced age and body wear and tear. Stopping aging remains impossible and therefore almost unimaginable. When we manage to imagine it, we only partially succeed; we envisage death from aging as defeated, but not the mechanism of senescence itself.

Finally, there is confusion between the concept of biological aging and the concept of entropy. Many people will say that degradation and aging are inevitable because any dynamic system, living or otherwise, necessarily ends up « degrading ». It is true that everything must stop, be exhausted one day, given the concept of entropy, but this relates to timescales that are totally different from the timescale of life. Living species such as redwoods or corals that do not have aging mechanisms do not « run out » through entropy. Nor do they « run out » like a watch reaching the end of its wound spring or battery.

Indeed, living beings are not « closed » systems. They absorb external substances and this can be done for millennia. Contemporary living beings are not affected by entropy, which will only have consequences in geological timeframes. For millions and even billions of years to come, a de facto unlimited source of energy will counter entropy on our planet. This is the energy of the sun.

An amortal life would almost certainly be a life in good health

The concept of amortality is by definition the removal of the aging mechanisms that cause death.

It is theoretically conceivable that, thanks to medical progress, one day we will be able to stop the aging process and prevent deaths, but only for people weakened by age.

It is theoretically conceivable, but in practice very improbable.

If one day we succeed in stopping the mechanisms of aging, the next or concomitant objective of researchers and medical bodies will obviously be to improve the physical and mental situation of the people concerned, to allow rejuvenation. When, in the medical field, we succeed in overcoming a disease (AIDS, cancer…) we also seek complete convalescence and we succeed more and more often, even if today it is still for a limited time.

Such developments are desirable for reasons of quality of life for older people and equal rights between young and old, but also in economic terms. A population that is growing and in poor health would be much more difficult for society to manage than an aging population whose health is improving.

The good news of the month, a personal story: How I will live to be over 57 years old thanks to the medical advances of recent decades

May 8, 2019 would probably have been the last day of the existence of the author of these lines (the main author of this letter) without the efficiency of the emergency systems and the Belgian health system and without the technological advances of recent decades.

I had the « good fortune » to have a heart attack in Brussels, where I live. The ambulance I called came in a few minutes and took me to a nearby public hospital where surgeons saved my life with a quintuple coronary bypass operation lasting more than five hours. And less than twenty days later, thanks to the equally brilliant post-operative care and the luck I have to have a good state of « remaining » health, I can have normal social activities, walk for miles… and write this letter.

I confess that in the ambulance that was taking me to my survival, I didn’t ask myself if it was moral to benefit from medical progress when a person living far from a big city, in Africa or elsewhere, would most likely have died (or even anyone who simply couldn’t reach the emergency services). Longevitists are sometimes accused of being selfish. In that sense, I was selfish. For the future, which continues for me after May 8, as in the past, one of my concerns remains, however, that longevity should concern all those who want it, as quickly as possible.


In the ambulance and in the hospital, I told myself again and again to what an extent today was the best time in human history to live a healthier life. I have also seen how remarkable healthcare, especially emergency care, is. I also told myself that today, even more than yesterday, it is urgent to continue research, to invest more money in the fight against aging so that more and more people can escape a « natural » death. It is so much more useful than spending time and energy on administrative issues, prestige, literally or metaphorically cosmetic issues or in conflicts over microscopic comparisons (knowing that I am certainly not immune to these « energy wastages », even after my adventure to the edges of life!).

I hope that in the near future, what has been possible for me will become possible for everyone, regardless of age and of where people live. I am convinced that if issues of health, longevity and more broadly everything that makes humans more resilient, became the glaring priority of this beginning of the 21st century, then progress could be dazzling.

For more information:
See: heales.org, sens.org, longevityalliance.org and longecity.org
Photo : Eos (Dawn) pursuing Tithonus

The Death of Death

Air pollution and longevity. The Death of Death. April 2019. N° 121.

 

I grew up in New-Zealand originally and I lived there until I was 12 years old. I remember one time my grandma came to visit us and I had never hung out with somebody who was over the age of 60 before. So, when she came, I remember for the first time realizing you know when I go and play with my brother you know I can run around and I could roughhouse. But my grandma, just getting up from a chair is really painful for her and that struck me as oh she has a disease. We should try to find a way to cure her so she can come and play with us. Then, I remember asking my parents what disease does grandma have and they said, oh she doesn’t have it, she’s just old. I was like « What disease is that? » And they were like. « No, no, you don’t understand it is a natural process ». And as a kid you’re just like that’s stupid. You know why is it a natural process that we should all get this disease that makes us so debilitated? Interview with Laura Deming, 25-year-old longevist researcher and investor. The Fight against Aging. HT Summit 2017.

Theme of the month: The influence of what we breathe on aging

Every day, we breathe in an average of about 12,000 litres of air, or 14 kilos. The air consists mainly of nitrogen (dinitrogen), a very small amount of carbon dioxide (0.03%) and about 21% oxygen, this substance that is essential to us but which, for most of life’s history, was a violent poison.

A molecule of dioxygen that enters the respiratory system will follow a path from the trachea to the blood, through the pulmonary alveoli, that is to say about 300 million tiny porous 2 square millimetre bags.

In addition to the gases mentioned, when breathing, we also unintentionally swallow a lot of substances, some of which are harmful to our body. Most of these substances will be released either almost immediately upon exhalation or by coughing or in the mucus that we evacuate by blowing our noses. But some harmful substances settle permanently in our bodies.

Although the term « pollution » sometimes covers natural substances (for example, those released in the event of a volcanic eruption), this letter will only consider the harmful effects of that which is produced by human activity.

Some of these substances can cause respiratory or nervous system disorders and even death by direct effect.

This is the case of the infamous mustard gas and Zyklon B during the two world wars of the 20th century, but it is also the case of many other chemical substances.

After the Second World War, air pollution in Europe which could be rapidly lethal developed, particularly as a result of the use of coal – which releases sulfur dioxide. As a result, what was called the Great Smog of London during the winter of 1952 (pollution so severe that visibility was sometimes reduced to a few meters) caused the death of thousands of people.

Globally today the dispersion of products with such harmful effects that they quickly lead to death is rare. However, there are still deaths, mainly in the case of accidents. Contemporary legislation on this subject is quite protective and a disaster comparable to what happened in Bhopal in 1984 with several thousand deaths is unlikely to happen again.

Another form of air pollution that has almost disappeared today is high-dose radioactive pollution. For three decades, from 1945 to 1974, hundreds of nuclear tests were carried out in the open air, releasing radioactive substances into the atmosphere in quantities and under conditions that we could no longer imagine today. There were notably around one hundred American nuclear tests 100km from Las Vegas and a Soviet test with a weapon 1,580 times more powerful than the Hiroshima and Nagasaki bombs combined.

But what remains very present, and is sometimes even increasing, in Europe and even more so in Asia, is pollution caused by so-called fine particles. These particles measuring less than one thousandth of a millimeter (one micrometer, colloquially one micron, symbolized by the µ) are introduced into the pulmonary alveoli. The smallest particles, more harmful, can even pass through the cells and into the blood. When these particles accumulate, they can cause inflammation, cardiovascular disease and respiratory diseases including cancer.

In the past, very small particles have already caused many deaths (and are still causing them), as in the cases of silicosis in miners and asbestos.

A very large part of pollution by fine particles comes from substances released into the home as a result of cooking or heating. According to the World Health Organization, this pollution causes 3.8 million deaths per year.

It is rarely covered in the media of our countries because it concerns almost exclusively the inhabitants of poor countries. Economic and technological progress would make it possible to rapidly reduce its impact as long as development choices are targeted at disadvantaged populations.

Also according to the WHO, outdoor air pollution, which also affects people in rich countries, causes 4.2 million deaths, the majority in Asia, especially in India and in China. In countries like France, this kind of pollution is generally going down but rather slowly.

The effect of air pollution on life expectancy

The significant impact on life expectancy must be clarified. The number of deaths counted by the WHO are « premature » deaths. Theoretically, a death can be « premature » by only a few weeks, which has a low impact on life expectancy.

Other studies do not only cite premature deaths, but also set a significant average loss of life expectancy, for example 10 years in New Delhi. A 1995 study measures the impact of air pollution on comparative mortality in cities in the United States. This impact is marked, even if clearly lower than the impact of tobacco consumption. However, when comparing cities and regions where pollution is higher today with other similar but less polluted cities and regions, the differences are small and not always in favor of less polluted areas.

For example, Flanders and the Netherlands have much higher levels of atmospheric pollution than other regions, but lifespans are not shorter there. The inhabitants of a fairly polluted large city such as Brussels, despite being poorer than the inhabitants of Wallonia, live longer (life expectancy in 2017 of 81.2 years in Brussels and 79.8 years in Wallonia). The city-region with the longest life expectancy in the world, Hong Kong (life expectancy 84 in 2018) is also a town with heavy atmospheric pollution. The state of Delhi, where pollution is one of the highest in the world, is the second longest-lived state in India (73 as opposed to 67 for the Indian average).

New Zealand is one of the parts of the world with the least air pollution and a country with a high standard of living and good social protection. In this country, life expectancy (82 years) is similar to that of equivalent countries with high pollution.

While smoking or not, being obese or not, living in a rich country or not, has a measurable effect on life expectancy statistics, the pollution variable is not very visible in terms of statistical comparisons. However, there is little doubt that breathing fine particles is harmful. The most likely thing is that the mortality rate caused is lower than estimated at current levels of pollution. Overestimation of the adverse effects of human actions is quite common in the contemporary world, whereas in the past these effects could be underestimated. It could also be that, overall, living in large cities, which are generally more polluted than the countryside, also has health benefits (better medical and social coverage, more active life, etc.).

Could our air quality explain the mystery of the supercentenarians?

The above comments concern the impact of pollution on average life expectancy, not on maximum life expectancy. Air pollution could well be one of the factors explaining « the mystery of the supercentenarians », namely the fact that the maximum lifespan of women and men has not increased for decades. It is possible that the accumulation of microparticles and the prolonged effect of exposure to anthropogenic toxic substances may offset medical advances.

There may even be a « silent killer » that we have not yet detected and that has an effect especially in the very long term. This could concern substances with little-known toxicity that gradually combine in the body to form toxic « cocktails ».

However, in this hypothesis, it remains to be explained why there are no longer extreme longevities in the least polluted areas of the planet with good medical coverage. According to the WHO, only 9% of the world’s population lives in areas exposed to less pollution than the recommended standards. These notably include New Zealand, already mentioned, where the oldest living person currently living is « only » 110 years old, while, for example, the oldest woman in Brussels is 111.

Research to be pursued for a common goal: a much longer healthy life than in the past

As we have written in this letter, much remains to be done in research on air pollution. One of the most uncomfortable aspects of research on toxic substances is the issue of low doses. Some argue that any dose of certain substances is harmful, without any threshold effect; others argue that products that are harmful at high doses have no effect or even a positive effect (hormesis) at low doses.

Debates at these levels are sensitive. Proponents of laissez-faire are quick to assert that there is an exaggeration of risk and will quickly make use of doubts about the medium and long-term effects of low doses to refuse any action. This is particularly true for exposure to fine particles. This refusal is all the more « tempting » for some because the most polluted areas are generally the poorest overall.

In this area, as in others, the precautionary principle must be applied in a proactive way. It is not a question of doing nothing and forbidding change, but of examining, better understanding and preventing the negative impacts of substances released into the air by both existing and proposed technologies. Upcoming monthly letters may address this subject to provide more information.

It is notably through better hygiene and environmental conditions that the average lifespan has more than doubled since the 19th century. The reduction in air pollution has played a positive role so far. Avoiding exposure to new harmful elements resulting from technological progress, or even, who knows, one day discovering useful breathable elements, concerns millions of lives today and tomorrow and is one of the essential aspects of thinking for a much longer healthy life.

The good news of the month: Undoing Aging in Berlin, the largest longevity science conference to date

From March 28-30, Undoing Aging, the largest conference ever held on research perspectives for a much longer healthy life, was held in Berlin. Some of the most renowned scientists not only exchanged with each other but also with journalists, activists and many potential investors. However make no mistake, it is exaggerated to say that the giants of Silicon Valley all want to « defeat death » and are close to it.

While the bubbling of ideas, enthusiasm and goodwill from Berlin and elsewhere is useful and spreading, current investments will have to increase, especially those from public authorities.

For more information:

  • Photo : Smog trapped under an inversion in Almaty, Kazakhstan

 

 

The Death of Death

The European Union and longevity. The Death of Death. March 2019. N° 120.

The world is going to change. The potential for a person’s lifespan in general is significant. According to the most conservative estimates, a person can live at least 120 years if they do not shorten their own lives and if circumstances do not shorten their lives. Declaration by Russian Health Minister Veronika Skvortsova following the meeting of the Presidium of the Presidential Council for Strategic Development and Priority Projects. (Translation, source TASS agency, July 10 2018).

Theme of the month: Europe and longevity

In no other demographic group of similar size do citizens live as long as in the European Union. Medical and social security coverage ensures an increasingly long life there.

While the most prominent research in the field of longevity and the most renowned scientists are often in the United States and the share of GDP devoted to health there is much higher, Europe is more advanced in terms of longevity.

In Southeast Asia, life expectancy is growing faster than in Europe, but only a small number of countries (Japan, South Korea and Singapore) currently surpass European countries.

European scientific research could allow for considerable progress in the not too distant future. Here are some reasons to envisage it.

A heavy legal framework, but one that allows for scientific research

We live in a world of extraordinary legal complexity. This is particularly the case in Europe. This complexity is motivated in particular by an unstable equilibrium between concern for the protection of citizens and the defense of economic and social interests of groups. One of the – probably temporary – outcomes of this complexity is the famous GDPR (General Data Protection Regulation) which came into force in May 2018. To simplify (greatly), it can be said that the purpose of the legislation is to prevent illegitimate and unwanted uses of data generated by citizens.
This complex text – whose application procedures vary from one state to another – does not therefore aim to prohibit the exchange and use of data for legitimate purposes and particularly for scientific research. In principle it is even the opposite – the GDPR aims to create a framework for legitimate exchanges. For example, for research, the European Regulation (in a « recital ») explicitly mentions that: It is often not possible to fully identify the purpose of personal data processing for scientific research purposes at the time of data collection. Therefore, data subjects should be allowed to give their consent to certain areas of scientific research when in keeping with recognized ethical standards for scientific research.

Given the complexity and length of the regulation itself and, above all, the millions of pages of transposition texts, doctrinal comments, judicial decisions, etc. that will result from it, it is not at all certain that exchanges will be facilitated (see for example the situation in Belgium). On the other hand, the clear principle of data protection from illegitimate uses can lead to a broader agreement among citizens to make health data available for research purposes. It is important that citizens are informed that it may be used in the general interest because they will then provide more accurate data. In addition, general support is important, especially in a democratic environment.

On the subject of public support, a survey published in March 2019 in Belgium produced an impressive result: 94 % of Belgian citizens are in favor of the use of artificial intelligence in the area of science and health and 56 % are willing to measure and share medical data via A.I.

Sharing of genetic data

Tens of millions of people around the world have already been sequenced. Most of these sequencings (normally prohibited except for medical reasons for people who live in France) are unfortunately very partial and carried out by private companies, the best known being 23 and Me.

But there are also sequencings for medical and scientific research purposes carried out with public funding and organization. It is in Europe that this is done the most. Major projects have been carried out or are in progress, notably in Estonia, Iceland, the United Kingdom and France (2025 Genomic Plan). A key element that the European Union could allow for is interconnectedness between these different data. In April 2018, the European Commission announced that 13 European countries had signed a declaration to allow cross-border access to their genomic information so as to have at least one million genomes sequenced by 2022. In less than a year, seven European countries have already joined the initiative.

Facilitating research through medical and health coverage

The member states of the European Union each have a fairly efficient health system, dense to very dense medical coverage, and different but effective systems for sharing statistical data. The diversity of populations, dietary, social and cultural habits, population movements, the multiplicity of systems for reporting medical and social information are all aspects that can be useful in discovering avenues in the field of longevity, thanks to data analysis.

European researchers and their use of artificial intelligence

The European Union is the region of the world with the most scientists, particularly in the medical field and the densest network of institutions and companies in the health sector. For scientific research, Switzerland is one of the closely associated countries, for example via CERN. A similar association should be possible for the United Kingdom if its exit from the European Union is confirmed.

As far as artificial intelligence is concerned, the European Union is not ahead of the curve in this area, but not particularly behind either, whatever some pessimists may say. In addition, Europe is at the forefront of ethical and practical reflection, particularly through the European AI Alliance, a forum engaged in a broad discussion on all aspects of the development of artificial intelligence and its impacts.

Longevity research

European and member state research in the fields of cancer and neurodegenerative diseases is numerous, effective and often publicly funded. The only aspect that is still missing in public institutions is the awareness of the universality of the aging mechanism and the need to combat it. This awareness is still limited to some private organizations, mainly in the United States.

One of the advantages of a rapid raising of awareness would be that knowledge acquired for a much longer and healthier life would be more collective, more accessible to all more quickly, European or non-European. The current situation in Europe has probably never been as favorable for this as it is today.

The good news of the month:
Progress in understanding regeneration.
Creation of an international academy for longevity research.

Researchers from Harvard have discovered the genetic process that controls the regeneration mechanism of marine worms that can « grow back » up to half of their bodies. Understanding these mechanisms is one of the fundamental avenues for human regenerative medicine in the years and decades to come.

The Academy for Health & Lifespan Research was established in February 2019. It is home to some of the most prestigious researchers in the field of longevity. The Academy aims, including through the organization of conferences, to raise public awareness of research advances and encourage increased public and private investment in research on life expectancy and health longevity around the world.

For more information:

In general, see in particular: heales.org, sens.org, longevityalliance.org and longecity.org

The Death of Death

Telomeres. The Death of Death. February 2019. N° 119.

 

Going beyond the known limits of our biology to extend life to extremes that are as yet unattainable is a dream that may be as old as humanity, but for the first time we have the right tools today to make it a reality in the near future. Genes and Longevity. The Challenges of Science (a publication by French national daily newspaper Le Monde). Page 11. 2018, translation.

Theme of the month. The limits of cellular divisions – cause or effect of aging?

At the ends of our chromosomes, there is a « non-coding » part, which has no known direct use, namely telomeres. With each normal cell division, part of this telomere disappears. When the number of divisions has been large, the entire non-coding area disappears and the cell can no longer divide properly. The limit of the number of divisions (about 50 for an ordinary human cell) is called the Hayflick Limit, after a biogerontologist who discovered this mechanism in 1965.

This limit does not apply to all cells. Stem cells escape from it, but so also, unfortunately, do cancerous cells. So it is that the cells of Henrietta Lacks who died in 1951 of a sudden cancer are used in thousands of laboratories and still reproduce, almost 70 years after her death, without limitation.

Many people have taken the limit to cell division as being the major cause of aging. When the cells can no longer reproduce properly, the whole body gradually degrades, inevitably. Moreover, Leonard Hayflick, when he tested the limit of cellular divisions, realized that the cells of older people were dividing less often.

Those animals with telomeres that last longer, have a longer life span (for example in the case of dogs or birds). In the same way, there is a correlation between telomere length and human life expectancy.

In the context of this explanation of aging, there is some good news. The length of telomeres can be influenced in various ways. For example telomerase is an enzyme that, during cell division, allows for maintaining the length of the chromosome by adding a specific structure at each end. Some companies sell products containing telomerase which are supposed to promote a longer life.

The most famous person among the experimenters in the field of longevity, Liz Parrish carried out a gene therapy in 2015. The human telomerase gene (hTERT), which regulates the activity of the telomerase enzyme upward, was injected in several places to facilitate its spread throughout the body. Liz Parrish states that the length of her telomeres has increased considerably, which would establish a biological rejuvenation, for this aspect, of more than twenty years.

Unfortunately, the mechanisms of aging are a complex phenomenon. A famous scientific article entitled « The Hallmarks of Aging » considers that there are nine main causes of aging. Aubrey de Grey of SENS Research Foundation has seven of them. In both theories, the question of the length of telomeres concerns only part of these causes. It is therefore very unlikely that telomere elongation has a fundamental effect on longevity.

But even a positive effect only allowing us to gain « a few » years of life is rather uncertain. In this respect, telomere length is much like many aspects related to aging. The direction of causality is uncertain. For example, hair discoloration and wrinkles are consequences and not causes of age-related impairment. Finding a way to maintain the length of the telomeres could, therefore, have no significant impact on other aspects of senescence.

In addition, one of the main aspects of aging is neurological degradation (Alzheimer’s disease in particular). And yet neurons divide very little or not at all

Finally, for some supporters of the theories of the seven or nine origins of senescence these causes form an interdependent whole and attacking one or the other cause without attacking the others will have no real effect. Much as a car cannot function if only one element does not work (a car does not run without petrol, or without tires, or without a transmission…), a human body can only function long-term if a solution is found for all of the causes.

It is certain that many, if not all, aspects of senescence are closely linked. It is also certain that, as far as maximum lifespan is concerned, we have not made any further progress in recent years despite all the medical progress. It is therefore almost certain that future research will be multidisciplinary and complex. It will, therefore, be exciting from an intellectual and scientific point of view, in addition to its immense potential usefulness.

The good news of the month: another longevity fund.

A new fund for investing in companies working in the aging field was recently launched, the Longevity Vision Fund, a $100 million fund. According to Fight Aging, from what was said and presented at the Longevity Leaders conference in London on February 4, 2019, it seems that the directors of the Longevity Vision Fund want to follow in Juvenescence’s footsteps, initially focusing on the discovery of small pharmaceutical molecules.  

For more information :

heales.org, sens.org, longevityalliance.org and longecity.org
photo: a chromosome and its telomeres

 

The Death of Death

¿ Viva la muerte ? The Death of Death. January 2019. N° 118.

In a song, Freddie Mercury sang « Who wants to live forever? »

Aubrey de Grey. We can ask ourselves the question! It’s like shouting out: « Who wants a million euros? » Everyone wants it, but no one dares to answer. People like to make it trivial because it allows them not to get emotionally involved. Since the window of time for this kind of research is very uncertain, as for any pioneering technology, they distance themselves from it. But deep down, no one wants to get Alzheimer’s. No one wants anyone else to get Alzheimer’s. And everyone would want there to be a cure. I think that gives you the answer to the question. Nice-Matin, December 18, 2018 (translation).

Theme of the month: deathism, thanatophilia, dolorism

What are we talking about?

Never ever, for the vast majority of humans and with regard to the vast majority of humans, will we wish another person dead.

If we see a person in danger of death and we are the only ones who can act, most women and men will try to save them even if there is a small risk to their own lives, even if it is someone they have never met and even if it is someone they do not love.

The right to human life is instinctively sacred, overriding all other rights, and our actions in such cases are instinctive.

But even if our act were reasoned, if we were warned « In 10 minutes, you will be faced with a situation where a person is in danger of death », we would do the same except that we would probably be more hesitant to risk our lives.

Similarly, if the warning said, « You will see an 80-year-old woman fall into the water », few of us would say, « 80 is enough, you have to make room for your grandchildren. Besides, this lady no longer has anything to contribute to society. Let her drown! »

However, this type of argument is widely used by opponents of longevity to explain why older people as a group, considered abstractly, must not live longer.

The purpose of this letter is not to dwell on the validity of the arguments, but to understand why citizens, who are very respectful of individual elderly citizens, do not wish to save them as a group.

A single death is a tragedy, a million deaths are a statistic

This expression attributed to Joseph Stalin is the first dimension of the paradox.

Throughout most of human history, we have lived in small groups. Solidarity was expressed above all in relation to the people we met every day. Then, since civilizations have existed, exchanges have widened, but solidarity continued to be expressed, mainly with people with whom we were in direct contact. More recently, solidarity has spread even further towards people who are foreign to us, but with elements of identification. The victims of an earthquake or other natural disaster may be far away, but photos or films make them identifiable and the exceptional nature of the event mobilizes us.

On the other hand, causes of suffering or mortality that have existed for a long time are less mobilizing, whether they be diseases such as malaria or age-related conditions.

A dead person we can identify is a tragedy, an unidentified dead person is simply a concept

When new technologies allow lives to be saved, we generally do not know in advance who will be saved. Lives saved are saved in an abstract way. What is more, the results if research do not come quickly. Tomorrow’s medical discoveries often do not yield results until later on. Finally, deaths due to aging are a slow, progressive, universal and still unavoidable mechanism.

One expression sometimes heard when talking about media mobilization in relation to deaths and therefore in relation to the energy put into avoiding them is the law of proximity or of the ‘death kilometer’. In reality what is even more important is the capacity to arouse emotion. Dutch-speakers use a specific word aibaarheidsfactor which could be translated as a sympathy factor (« caressabillity »). The more « photogenic » a person in danger of death is, the more we care, even to an absurd or unhealthy extreme (such as a child falling into a well mobilizing dozens of television cameras and millions of people who were entirely unable to help in any way). On the other hand, the less « photogenic » the person is, the more their risk of death is banal, and the lesser the mobilization.

Medical progress is uncertain

To return to the individual example given in this letter, if we were in front of a person in danger of death, but not sure if we could save them, we would still try to save them, probably with more energy than if it had been a certainty.

On the other hand, when it comes to saving unspecified people without having certainty, there is less energy.

Dolorism

Dolorism refers those who get enjoyment from their pain; who find pleasure and justification in it. Not all dolorism is linked to death, and medical progress has been made in alleviating suffering, but the dimension of a kind of « accomplishment » by a painful end remains strong.

Thousands of pages have been written by all those who consider that death in general and death by aging in particular is what gives interest to life.

It should be noted that, for most believers, this view of the beauty of a short and painful life is accompanied by an immense paradox since, after death, there is an eternal and often paradisiacal life (Christians, Muslims, Jews) or a return to cycles that can be countless and extremely long (Buddhists, Hindus).

As already written, except in very rare cases, this reasoning is first and foremost a collective reasoning. Almost no one claims to wish the death of their parents or relatives. It is also a reasoning affected by a status quo bias. Almost no one claims that life would be better if it were shorter, as short as it was two centuries ago, for example. On the other hand, many are opposed to extending life « excessively ».

Deathism and thanatophilia

To designate those who wish that life should not be lengthened (much) by medical progress, English-speaking longevists generally use the term deathism which in French we may translate as mortalisme. It is the acceptance of death (by aging) which is not only perceived as inevitable, but also as necessary, admittedly unpleasant to go through but with undoubted benefits.

The term thanatophilia can also be used in a sense that places more emphasis on the desire for death. Those who consider death necessary, however, will generally say that it is a useful, but not in itself desirable.

Terror Management Theory – Mortality salience

In fact, it is conceivable that the underlying reason for being mortalist is that today we have no choice. If we escape other causes of death (which are becoming increasingly rare), we will die of old age. Dying of old age is an unbearable and inevitable fate. We cannot look either the sun or death in the face (La Rochefoucauld). So, at the same time, we try to forget our final fate and try to transform it into something positive. Be careful, this process happens unconsciously. When we start to become aware of it, its impact decreases. This phenomenon, discussed in a 2010 letter, is called Terror Management Theory or sometimes Mortality salience.

It is necessary for our psychological equilibrium that we should know how to live with the inevitable. But today, as we progress in the fight against age-related diseases, making excuses for death from old age and the pain caused by senescence can have the effect of slowing down research against aging.

Conclusion

If you read this letter on a day in 2019, in the last 24 hours, about 110,000 people have died from age-related diseases. They have often died under conditions that you would not impose on your worst enemy if you had the opportunity.

If you read this letter a few decades after 2019, perhaps aging has joined the plague, cholera, famine, in the great concert of sufferings that have become increasingly rare.

The theologian Reinhold Niebuhr, in his Serenity Prayer, asked for the grace to accept things that cannot be changed, to have the courage to change those that should be changed, and the wisdom to distinguish them from each other.

The dizzying technological advances make these distinctions more complex. We must accept today’s situation with serenity and try to change it tomorrow. Media and psychological mobilization leading to scientific, environmental, health and social welfare progress… could enable millions of older women and men to live better and longer in the not so distant future. Perhaps we can even more easily accept today’s sufferings knowing that tomorrow we will be less subject to them.

The good news of the month: More financial resources for research for longevity

As the excellent online periodical Fight Aging indicates, more and more money is  being invested in biotechnology businesses in the field of longevity science.

There are traditional venture capital funds, such as the Longevity Fund, technology funds such as Kizoo Technology Ventures and Felicis Ventures; there are also private equity / business development companies like Juvenescence and Life Biosciences.

Hundreds of millions of dollars and euros are being invested for profit, but also for potentially useful health benefits for all, especially if governments also start investing in our future, that of our children and even that of our parents.

For more information:

 

The Death of Death

When life suspends its flight. December 2018. N° 117.

The death of individuals is the way species adapt to changes in the environment through natural selection. Once mankind will have full control of its environment, death will no longer have the same reasons to be. Because of the Baldwin effect, natural selection will continue to act on genes. It will favor longevity. It will promote longevity. This one will therefore continue to increase steadily. Extract from « The Thermodynamics of Evolution » by François Roddier.

Theme of the month: dormancy, hibernation… and lives naturally lived in slow motion

Cellular organisms have been living, reproducing and dying for hundreds of millions of years. Hundreds of millions of life cycles have followed one another. Life, as we intuitively understand it, is a set of complex mechanisms by which each entity maintains its integrity, maintains its metabolism, through multiple and abundant exchanges with the outside world.

But in many living species, under certain circumstances, life (to paraphrase the poet Lamartine) « suspends its flight ». In other words, the metabolism slows down considerably.

This letter will detail the main categories of « natural » slow-motion lives, with the exception of sleep. (This fascinating way of living in slow motion that we experience every night was addressed in a letter in January 2016.)

Hibernation and dormancy

Hibernation is the most common case of slowed-down life. During the cold season, some mammals, including marmots and a species of bird (the common poorwill), take refuge underground or in crevices and live with an extremely slow metabolism: body temperature at one or two degrees, heart rate of a few beats per minute…

For poikilothermic (cold-blooded) vertebrates, a similar phenomenon is called brumation. The wood frog can even survive partially frozen. For insects, the mechanism similar to hibernation is called diapause.

Finally, as we all know, many plants lose their leaves in winter (or in the dry season). The technical term is a deciduous plant and the period of slowed-down activity is called dormancy.

Grains and seeds

In this case we are talking about such a « slow » life that we do not generally consider it life at all. Under normal circumstances, for plants living in areas with different seasons, a seed will have a virtually non-existent metabolism during the season that is not favorable to growth.

The term dormancy is also used here. Usually, dormancy lasts only a few months and the plant is « born » in the summer. But if the germination conditions are not met but preservation conditions are good, some seeds can remain fertile for centuries and even millennia. Some seeds from a date palm found in the fortress of Masada in Israel germinated after two millennia.

Spores

A spore is a tiny entity usually made up of a single cell that can give rise to an organism. Many algae, fungi, protozoa and plants produce spores.

In ideal preservation conditions, a spore can produce an organism after thousands of years. It even seems that bacterial spores can remain inside rocks for millions of years. The record is said to be 240 million years. However, this is not certain. In the case of such extremely resistant forms of dormant life, it may be that the spores arrived by « contamination » when the rocks were examined.

Underground life

According to a very recent statement by the Deep Carbon Observatory, an almost inanimate microbial ‘zombie’ life is maintained for millennia at great depth (up to 2 kilometers underground). The total biomass is estimated to far exceed the weight of humans. At lesser depths, in the Siberian permafrost, there have been found nematode worms that were « brought back to life » after 40,000 years.

But this is not transferable to humans

All this reminds us how living beings are often more resistant than humans and to what extent death from aging is not a universal phenomenon. The study of the mechanisms of these longevities will not give us direct instructions for a longer human life, but can give us ideas so to allow us one day to have more resilience.

New of the month: Did Jeanne Calment really live to be 122?

The small world of specialists in extreme longevity is being rocked by controversy. Some are stating that Jeanne Calment, who died in 1997, was an impostor. Officially her daughter Yvonne died aged 35 when Jeanne was in her sixties but some people think that in fact the daughter was switched with the mother. The person known as Jeanne Calment therefore actually died shortly before reaching 100, it is claimed.

In support of the claim:

  • There were no other centenarians in the Calment family. And yet the genetic aspect is important in centenarians.
  • The supposed age reached by Jeanne Calment was and still is totally atypical (more than two years older than the second longest-lived person).
  • Jeanne Calment was rich and there was therefore an advantage, in particular, to hiding her death so as to avoid inheritance tax. Jeanne Calment has also remained famous for having sold her home en viager [an arrangement where the seller stays in the home for life and receives a lump sum and ongoing payments from the purchaser]. This type of contract is uncommon, but it would make sense if there had been deception over Jeanne Calment’s death.

On the other hand:

  • Jeanne Calment’s case is abundantly documented. In the event of fraud, at least Jeanne Calment’s husband should have been aware of it almost certainly as well as other family members and relatives.
  • It seems unlikely that Yvonne Calment, who supposedly pretended to be Jeanne Calment, could have lied (or possibly after a while lied to herself) for more than 60 years without anything wrong being detected despite her very numerous contacts, notably with journalists.
  • The person who was to receive Jeanne Calment’s property upon her death would have had every advantage in reporting the fraud because he could have had the life annuity canceled. At the death of this notary, his widow who continued to pay would also have benefited.

So there are good reasons for doubt in both cases. It would be useful for science to analyze the DNA of the person buried in 1997 (by comparing it with the DNA of family members). If Jeanne Calment did live 122 years, we will have extremely useful genetic elements to decipher and, if not, we will know that supercentenarians are an even rarer phenomenon than we think today.

Unfortunately, research for longevity is not yet perceived as important enough. It is easier to examine the DNA of royal families than that of presumed supercentenarians.

To find out more:

 

 

 

The Death of Death

Some social and cultural perspectives on rejuvenation therapies. The Death of Death. November 2018. N° 116.

Should mankind be augmented? If it’s for all of humanity, I’m for it. In the current context, we are promised by transhumanists that all this will happen (around) 2020 or 2030. But between now and the next 10 years, we are already in the midst of extremely rapid change. And the question of augmented mankind must enable us, at least I hope so, to go beyond these great advances in medicine and technology, which are undeniable and will bring us a great deal. I think that this will indeed only be possible – the augmented human – if it is in the context of an augmented humanity. Pascal Picq, paleoanthropologist and writer, source Le Figaro (video of a talk, translation), October 1, 2018.

Theme of the month: Rejuvenation and Society

Very often, those to whom we talk about human longevity imagine a world of decrepit old people with no energy. However, scientific research on aging aims to reduce and even stop the aging processes.

If we succeed, women and men will be able to live much longer in the same state of health as they were when treatment began.

Or rather, it could go far beyond that, the search for therapies to stop the process could be continued and allow rejuvenation, a decrease in the visible age.

The hope of rejuvenation through the intercession of divine powers, especially in the myth of the Fountain of Youth, is probably almost as old as that of a life without aging.

For centuries, women and men have also dreamed of products that could restore the beauty and vigor of youth. Today as in the past, in the cosmetics industry, hundreds of billions of euros, dollars and all the world’s currencies are spent on product research and even more on advertising these products to improve physical appearance. But all these cosmetic agents are in principle only effective… cosmetically.

Finally, the hope born of purely medical research is also ancient, from testicle transplants to stem cells. However, despite many promising attempts and even more dramatic announcements, in this year 2018, no substance, no therapy, has a proven long-term rejuvenating effect for humans (or indeed for any mammal).

But today’s impossible could become the banality of the day after tomorrow. In 1900, thousands of attempts to fly « heavier than air » had been unsuccessful. Twenty years later, at the end of the First World War, aircraft had been used for countless purposes, from dropping bombs to passenger transport and peaceful mapping to the identification of military targets.

In the rest of this letter, some issues and the potential social, political and cultural consequences of rejuvenation techniques will be discussed.
What age would we choose? The physiological aspect.

Mortality, and to a lesser extent morbidity, increases with age, and exponentially. The most desirable physiological age from this point of view is about 20.

In a world of optional aging, there would probably be a few unconventional people not taking rejuvenation therapy. On the other hand, logically, those wishing to « surpass nature » would probably go as far as the ideal physiological age and would not stop on the way. To draw a parallel with the current situation, there are a few (very few) people who do not cook their food or use mobile phones. Even fewer still cook their food halfway or use a mobile phone every other day.

What age would we choose? The aesthetic aspect.

We have never yet been able to « uncouple » the aging process that allows more experience and the aging process that causes the deterioration and then the death of every human being after a maximum of 122 years. The passage of time to gain experience is of course positive. There is a famous African proverb that says that when an old man dies, it’s a library that burns to the ground.

It is therefore conceivable that the women and men of the future will prefer to have a physical appearance of a mature person rather than a young person. However, it is also possible that age may be marked by signs other than those of the body, such as the appearance of clothing. Moreover, at present, differences in physical appearance between the ages of 25 – 30 and 45 – 60 are tending to diminish thanks to overall progress in public health (medicine, diet, lifestyle, etc.).

Parents and grandparents physically resembling their children: would that be disconcerting?

Some may regret the « good old days » when people over 75 were so physically different. They would be deprived of the « beautiful natural spectacle » of progressive degradation.

Theoretically, we could also fear a society of « perfectly young and beautiful », uniform, bland and interchangeable humans.

But strong uniformity is unlikely. Both in terms of physical characteristics and clothing, not to mention personality, it would be logical for citizens to bring out their socio-cultural environment, which of course includes the period during which we grew up. To imagine what could happen, the science fiction film « In Time » is interesting. In this film, citizens experience an eternal physiological youth (but die if a computer clock orders it). As for as everything else goes, society is composed, as it is today, of « nuclear » families (father, mother, children). Quite quickly the viewer clearly « feels » who the children are and who the parents are, whereas all of them are physiologically young. In other words, a society can easily mark the age of its citizens without the need for physiological appearance.

We could also imagine that some people would go through phases of different physical appearance, older and then younger or the opposite.

Rapid changes or sudden changes?

First, we must make a remark based on pure logic. No matter what happens, no one will be more than 200 years old before the year 2100. This is obvious, but it often eludes those who are concerned about the potentially « upsetting » nature of rejuvenation therapies. Indeed, the oldest person in the world is 115 years old today and will only be able to reach 200 years of age in 2103, whatever happens. Even if a perfectly effective therapy were to be discovered tomorrow, it would take decades for a significant number of citizens to live longer than 122 years (the maximum lifespan ever reached so far).

At the same time, if therapies allow rejuvenation, they would probably only allow gradual changes. And even if it were technically possible to change one’s appearance overnight, it is likely that the majority of citizens would prefer gradual changes for themselves.

Obligatory rejuvenation or optional rejuvenation?

Those who oppose longevity research often say that stopping aging and dying of old age is impossible (they are right) and will always be impossible (they may well be wrong, but only time will tell). This statement is often capped off by a somewhat contradictory statement such as « I want to still be able to choose to grow old ».

This type of declaration is illogical at two levels.

First, to date, no one chooses to age or not to age. We cannot choose to age any more than a stone endowed with consciousness could « choose » to fall.

Secondly, and most importantly, if rejuvenation therapies are developed, they will not be any more mandatory than it is now mandatory to receive treatment when we have an illness. Initially, few people would take the therapies. Then the movement would spread. As rejuvenation therapies become more widespread, the fundamental right to a healthy life should appear more and more important. Deterioration due to old age could become as undesirable tomorrow as plague and cholera are today.

In this case, an old man who dies would become an exceptional event. Almost all of us would have more time to increase our knowledge, the number of projects we undertake with others, our capacities, and more time to teach and cooperate with those who are the youngest « chronologically ». We would also have more time to ensure that the entire planet is a sustainable environment that can support a long life. Life would also become an increasingly precious commodity as our time horizons expand.

At the same time, it would also be important, to be democratic and pluralistic, to allow those who wish to continue to age to do so, like the Amish in the United States who do not use certain technologies.

Eternally young, a deadly bore or a wider field of exploration than ever before?

Millions long for immortality who don’t know what to do on a rainy Sunday afternoon wrote British novelist Suzan Ertz.

It is not impossible that one day longevity will be boring and that some people will decide to age again. But in fact, boredom affects as much, if not more, young people who have only « a few years on the clock ». Older people are often less bored, although their physical capacities and activities are decreasing. The taste for life would be even greater if people of advanced age were to benefit from rejuvenation treatments.

A world of women and men choosing their biological age would not, however, make the world perfect. This would be a world to be improved with environmental, technological, social and cultural challenges. It would also be a world where we could « de-haste » ourselves, take time, consume less frenetically, be less competitive and collaborate more with each other.

                                The good news of the month:
The Eurosymposium on Healthy Ageing was a success

From November 8-10, around 100 researchers and research activists for a much longer healthy life met up in the centre of Brussels. This was an opportunity for high-level scientific exchanges, but also for discussions about the financial perspectives (how to find funding for the most promising research) and even political perspectives.

Notably, we may see some pro-longevity candidates in the May 2019 European elections.

To find out more:

 

  • Photos : Antonin Kovar aged 25 and 102

 

 

The Death of Death

Senolytics. The death of death. October 2018. N° 115.

The search for life-prolonging interventions has often been perceived as a purely academic pursuit or as an unorthodox medical enterprise, with few or no practical results.

Yet, in fact, these studies, which explicitly aim to prolong human life, have often been a formidable, albeit rarely recognized, motivation for biomedical research and discovery. Ilia Stambler, June 2014 in The unexpected outcomes of anti-aging, rejuvenation, and life extension studies: an origin of modern therapies

Theme of the month. Products that destroy senescent cells.

There are many more cells in our body than human beings who have lived on the planet, probably around 40,000 billion. These cells reproduce by dividing, grow, die, absorb and excrete substances… In short, they are living entities that function in our body with a certain autonomy and for an extremely variable duration that can range from a few weeks (120 days for red blood cells) to a whole human life (most neurons).

As far as we know, our cells are directly descended from an organism that appeared nearly 4 billion years ago. More precisely, our cells come from the fusion, two billion years ago, between two descendants of the original organism: the primitive cells and what are today the mitochondria.

When a cell malfunctions, it is normally eliminated quickly. There are many mechanisms that lead to cell death, the best-known being apoptosis sometimes also called “cell suicide”.

But it also happens that cells that are harmful to the rest of the body continue to live. The most well-known case is cancer, an « anarchic » multiplication of cells that results in the death of the carrier individual if the body’s control mechanisms or adequate therapy do not interrupt the multiplication.

Senescent cells

Another major category of cells in poor health has been the subject of great attention in recent years by researchers working in the field of the fight against aging. These are the so-called « senescent » cells.

Substances used to destroy these cells are called senolytics. The term is based on the word « senescence« , i.e. in biology, the process of progressive degradation due to aging, and the word lysis which refers in particular to the degradation of organisms by the action of a physical, chemical or biological agent.

A senescent cell is a cell that does not function effectively for the rest of the body. It has a metabolism whose functioning has harmful consequences for the rest of the body. It accumulates and secretes pro-inflammatory factors that promote the development of age-related diseases.

The objective of the ongoing research is to destroy these cells, but of course without significant negative effects on healthy cells. This is therefore a goal quite close to that sought in the fight against cancer, where it is necessary to eliminate cancer cells without eliminating healthy cells. Products designed to destroy cancer cells are also being tested as senolytics.

Many substances have been tested in recent years on mice and some products are beginning to be tested on humans. Treatment with senolytics results in targeted apoptosis of senescent cells. It should be noted that it is not necessary to remove all senescent cells but only part of them. It is even possible that a treatment that killed all senescent cells would be counterproductive. Successful treatment reduces inflammation. On the positive side, arterial calcification is lower, reducing the risk of atherosclerosis.

To date, a positive effect has been established for mouse health levels in the short and medium term. One experiment yielded positive results with regard to the lifetime of mice, which increased by about 25%.

Tested products

Quercetin (a flavonoid) and Dasatinib reduce the « markers » of senescence in in vitro and animal studies. The anti-cancer drug Navitoclax was also examined as a senolytic.

Another flavonoid, fisetine is currently mentioned very frequently in scientific exchanges related to these new therapies, as are piperlongumine and Bcl-2 inhibitors.

Perspectives and limitations

Senolytics are currently the most frequently cited therapy in the field of research on aging. These are already-existing products, often natural (which are not very expensive to produce), whose mechanism of action is fairly well known and which could significantly extend healthy lifespan.

However, optimism about this should not be excessive. Most experiments on mice to date have not focused on longevity. The first human trials widely announced in the scientific community are only just starting. They will be double-blind and will concern elimination of senescent cells from the joints of osteoarthritis patients.

In this field as in other longevity research, greater public and private investment, faster knowledge sharing and the involvement of more researchers is desirable to enable those who wish to live in good health much longer to do so in as near a future as possible.

The good news of the month: More and more international activities concerning longevity.

There are so many activities informing researchers about human longevity that it is no longer possible to follow everything. Two conferences in Europe have recently taken place and two conferences are taking place in November:

To find out more: