[Quoting Shakespeare] As flies to wanton boys, we are to the gods; they kill us for their sport. Soon the science will not only be able to slow down the aging of the cells. Soon the science will fix the cells to the state [‘return them to their original state’?] and so we become eternal. Only accidents, crimes, wars would still kill us. Eric Cantona, 29 August 2019, in a slightly off-beat speech, when asked what was going through his mind, on the occasion of him receiving the UEFA President’s Award 2019.

Theme of the month : Experimenting for longevity, right or duty?

Over the last few decades, societies have gradually developed a huge web of legislation to protect the health of people who undergo experiments; to a point that is no longer favourable either for medical progress or for people who wish to experiment for the common good.

Medical research in the past

For centuries, experiments involving humans were conducted with far less respect for the rights of the people undergoing the experiments than were accorded to other citizens.

The results of medical research starting from the Renaissance and especially in the 19th and early 20th centuries were extraordinary. But the lack of respect for the human rights of those undergoing experimentation was often also spectacular.

For a long time, very often, it was convicts who were ‘made use of’, cut up… At times when the death penalty was still common, this could be a way to escape the ultimate penalty. But this is all the more potentially unenviable especially since anesthesia had not yet been practiced.

In addition to those convicted by the courts, there were people with fewer rights, particularly from black Africa. For example, a doctor from the southern United States, James Marion Sims, James Marion Sims first experimented on black female slaves before operating on white women.

But when the subject of unethical medical experimentation is brought up, it is above all the atrocities committed during the Second World War, including those of the infamous Docteur Mengele, that we think of. He was responsible for dozens of deaths of women, children and adults. Those which were committed by doctors of the Japanese Imperial Army of Unit 731 are less well known. And yet the experiments were carried out under even more abominable conditions and caused thousands of deaths. What is more, most immorally, there were very few prosecutions after the war and no convictions of the main perpetrator Shiro Ishii.

It is these atrocities that were the trigger for strict legislation. But these developments were gradual. For example, until the 1970s the American authorities continued to experiment on African Americans.

The contemporary situation

Today, at least in the countries where the majority of medical experiments take place, legislation is very strict, mainly expressed in the Helsinki Declaration. By a kind of excessive pendulum swing, a person who is subject to clinical trials is better protected than an ordinary citizen. In order to carry out a trial, the organisation concerned must in particular be authorised to do so, the trial itself must have been accepted by an advisory body, and the “testers” must have given their « informed » consent, which means completing numerous and complex documents. It is also necessary, of course, that the health risk for these testers is not considered to be disproportionate.

Then the study itself consists of several phases. After establishing its probable safety, usually in animal trials, the same safety should be established in a group of people without testing efficacy (Phase I). Only then is the effectiveness of the treatment itself examined, first in a small group, then in a larger group, compared to another treatment or placebo (phases II and III).

The result of all this is that testing is extremely time-consuming and expensive. As very often trials are carried out by companies linked to the pharmaceutical world, investments are mainly made for patentable products and methods and with great difficulty for others. This explains, for example, why a longevity experiment on metformin took years to organize due to lack of resources.

However this slowness issue must be qualified. Accordingly, in the context of the Ebola epidemic some trials were carried out much more quickly. In the event, two aspects probably played a role:

• Fear of lethal consequences of the epidemic for the populations concerned and of the possible spread to other continents.
• And, in a much less ethically understandable way, a lesser concern for the rules of protection when the subjects of the trial are in Africa.

Areas for improvement: duty to share data and duty to experiment

At present, many people consider that medical data belongs to patients. Those responsible for carrying out the treatments could therefore not use them without consent. This is understandable when the data could be used « against patients », for example by an insurance company or an employer. But can the same be said for the results of medical research, which can be useful to everyone, starting with the weakest? Assuming that I possess a type of blood that is unique in the world because of its coagulating properties, would it be fair if I refused the use of this data, condemning people to death because they could not benefit from certain medical advances?

The answer should be obvious. Moreover, in practice, in the vast majority of cases, the formulas for consent to data sharing are bureaucratic red tape. It amuses lawyers above all, or more precisely, it provides them with a source of income without creating real consent, since almost everyone signs and almost no one reads it (and those that do read it will not make much sense of it).

In an ideal environment, the first question asked would be « How can we ensure that medical research allows a longer and healthier life for those who want it without harming those who provide the information?” All of us as patients would have a moral duty, even a legal obligation, to share our data. There would also be a strict obligation for organizations using the data to share results for scientific and therapeutic use and an equally strict prohibition on using the data for other purposes.

We would therefore all become testers without any additional effort, by pooling information on all aspects of the billions of medical procedures (surgery, drugs, tests, etc.) we undergo each year. This may seem worrying to some, but it can also be seen as reassuring because it allows more access to data and therefore more control. This sharing is already partially done in some countries, particularly in France. Indeed, much medical data is shared through, among other things, the National System of Health Data, but with an insufficient degree of accuracy.

It should be noted that this perception of the desired use of medical data is tending to spread quite rapidly, particularly in France. As medicine becomes more and more computerized, it depends more and more on accessible digital data. It is becoming increasingly clear that it would be immoral for a patient benefiting from the data of others to refuse to give theirs to others.

At the same time, however, medical trials will still be necessary.

A first means of acceleration could be self-experimentation. It has been quite frequent in the past and it still exists. For example, the controversial Liz Parrish as well as the renowned biogerontologist Greg Fahy have practised it.

But the main avenue is faster testing with more realistic rules on many aspects. It should be noted that speeding things up can be more of a guarantee of protection for those who will be the subjects of the tests. This is the case when information is shared more quickly, without being « blocked » because of rules on excessive appropriation of intellectual property rights or other reasons. What is needed, notably, is to have a more wide-ranging approach, ideally international, and to have a globalized ethical authorization procedure. Above all, what is needed is awareness of the urgency, once it is established that the probability of achieving the objective is no longer negligible.

Conclusion

Every day, 110,000 people die worldwide from age-related diseases. Effective testing must focus on the oldest (on young people, it would take years or even decades to see sufficiently convincing results). Elderly people should have the right to take part in experiments, and in better conditions. We may even consider that, for older women and men who are informed and who have the financial, social and psychological means to do so, it is an ethical duty; a duty of assistance of the same order as the duty we may feel to give our blood in the event of a disaster.

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Good news of the month : Trials of metformin for longevity are about to begin. A trial with 5 « rejuvenating » products indicates a positive result.

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The « TAME » project, that is to say a trial on positive effects of taking metformin by elderly people in good health is going to start in the United States. It is a piece of good news that must be tempered by the fact that this start has been awaited for two years now due to lack of funding.

An extremely promising one-year trial of five products with a small group of men aged 51 to 65 has succeeded in establishing in this group a 2.5 year average increase in the age indicated by « epigenetic clocks ». In other words, it appears that rejuvenation is demonstrated over the two year period for people taking these products. This is extremely promising, but must be confirmed by larger-scale experiments.

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To find out more :

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

Painting : La vaccine ou le préjugé vaincu, 1807 (vaccination, or prejudice vanquished).

Sovereign, my master, aging has come, old age has struck down, exhaustion has arrived, weakness keeps returning. Every day is spent sleeping, as if one had gone back into childhood. Sight is worse, he becomes hard of hearing, strength is lacking, the heart is weary, the mouth is silent, it no longer speaks, the heart is no longer in it, he no longer remembers yesterday, all the bones are suffering, the good is transformed into bad. Every taste disappears. The impact of old age on humankind is bad in every respect. The nose is blocked, it doesn’t breathe anymore, it’s as painful to get up as it is to sit down.

Thus, 44 centuries ago, did the vizier Ptahhotep, who was going to take on an « old-age stick », i. e. an assistant, describe to King Djedkare Isesi at 110 years old the infirmities that were beginning to overwhelm him. The Age of 110 and old-age among the Egyptians. Gustave Lefebvre. 1944. Note: it is explained in the article that these were invented lifespans; no Egyptian of antiquity probably lived more than a hundred years.

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Theme of the month: Living longer, an inequality in favor of women?

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Differences among animals

In many animal species, there are sex differences when it comes to lifespan. These differences can be dramatic, for example, in the case of social insects. Certain queens of an ant species can live up to 30 years, while males die quickly after fertilization, a few days after reaching adulthood.

Among animals in general, sex differences are mostly not significant. A distinction must also be made between the average or normal lifespan, lifespan in the wild and maximum lifespan protected from the elements and predators in captivity. For lifetime in the wild, the strongest animals (which can be the females or the males depending on the species) live longer. In captivity, it tends rather to be the smallest animals that live longer.

In some species the time of reproduction is the end of life, the most well-known and spectacular example being that of salmon. Sometimes females can live longer so as to bear the next generation. This is the case for the antechinus, a kind of marsupial. The female will survive until the young can become autonomous and sometimes the female may even have a second litter. As for the male, it has the shortest life of all mammals, less than a year, a life that ends very soon after reproduction.

One factor that could create a significant gender difference, namely the menopause mechanism, exists, outside humans, only in some cetaceans, including killer whales.

Differences between women and men: the natural and the cultural

It is widely known that women today live longer on average than men. Thus in France in 2017, life expectancy reached 85.4 years for women and 79.5 years for men. This is, of course, due in part to the fact that maternal mortality in childbirth has become a very rare event. While slightly more men than women are born, the number of women on the planet exceeds that of men. Until a few decades ago, sex difference was first evident in the higher number of deaths of young boys than girls. Today, except in the poorest countries, infant mortality has become low or even negligible and it is mainly in later life that differences become noticeable. In France in 2018 58% of people aged 80 were women, 69% of people aged 90 and 81% of centenarians. Among the very few people aged over 110 there are almost no men. The 10 people who have lived (in a proven way) the longest in the history of humanity are for that matter women.

In all the countries of the world apart from who extremely poor ones (Mali and Eswatini, formerly Swaziland), women live longer on average than men, despite having a standard of living, including access to healthcare, which is often lesser than that of men, especially in old age, often synonymous with isolation.

Life expectancy, both average and maximum, is, therefore, an area where it is better to be born a woman than a man.

The causes of these differences are almost certainly biological but there are also socio-cultural reasons:

• less risk-taking, for example, fewer deaths in car accidents;
• less violence, especially fewer murders (committed, but also suffered, despite feminicides);
• fewer suicides; 
• less tobacco and alcohol consumption.

In many rich countries with long life expectancies, life expectancy for men is increasing more than for women and therefore the difference in life expectancy between women and men is decreasing. This is probably due to a cultural reason, namely that the behavior of people of both genders is becoming more uniform, but perhaps also because without ground-breaking medical progress we can hardly progress in life expectancy any more and therefore those who are « at the top » no longer climb up much.

 Finally, also much less positive, according to statistics on healthy life expectancy, the part of life without significant health problems is generally lower among women. With regard to inequality in the face of suffering and non-fatal diseases, some of the explanations are certainly cultural, particularly the poorer medical cover and assistance for elderly women. But biological differences can also explain this situation, particularly the profound transformations that occur during menopause. According to a recent study by Austrians, it appears that women’s faces change more quickly than men’s after the average age of 50, the average age of menopause.

Castration, a recipe for longevity?

This paragraph is not supposed to be taken too seriously. As they say, Don’t try this at home. Some people believe that the removal of male hormones has a positive effect on longevity. A 2012 study found that eunuchs lived longer than other people whose age of death was known in Korean royal palaces. However, this could be due first of all to the better treatment of these people compared to the « ordinary » members of the entourage of the Korean leaders of the past.

In a much less invasive way, some have proposed hormone injections as a way to promote longevity. But as there are major effects on physical appearance there have been no large-scale experiments with men taking female hormones.

 It should be noted, with regard to sex and longevity, that sexual abstinence has often been proposed as a means of longevity, of « preserving energy », with this being seen as complementary to various religious factors, for example in Taoism. However other sources suggest that a regular sex life, within reason, promotes longevity.

Today a lot more people are changing sex than used to be the case. It is as yet too soon to estimate the impact on life expectancy. And psychological and social circumstances will very probably have a major impact in this area before the purely physiological aspects.

Future avenues for a much longer healthy lifespan for women… and for men. 

The difference in life expectancy can be explained in particular by better behaviors and a better lifestyle (in the case of women), despite generally less favorable conditions. Modest gains in longevity are possible for men by examining differences and imitating what women do.

And yet all too often medical experiments only concern men. And even as far as animal experiments are concerned, very often they are only carried out on male animals. It is obviously harmful to women not to observe specific health issues, but also potentially for all humans.

When it comes to significant gains in longevity, the difference in maximum life expectancy can ultimately be explained by genetic factors. There are differences between women and men. We know that many genes are associated with longevity and we know that almost all men and women differ in the presence of two Y chromosomes in women and an X and a Y in men.

To date, no « longevity gene » with a significant impact has been found on the X or Y chromosomes (or indeed on any gene). It is probably more likely to be due to the combination of genes. Research that focuses on the potential sequencing of millions of people may be able to detect some.

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The good news of the month: The World Health Organization (WHO) is asking people for their views about a decade of « healthy aging »

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The WHO has announced that the 2020-2030 decade will be devoted to healthy aging (but the term longevity would be preferable to aging). It invites citizens and organizations to take a position on this issue. Several international organizations have spoken out in favor of making biomedical research for a much longer healthy life the priority for progress in this area.

If you wish to you may support or take inspiration from the position of the International Longevity Alliance so as to express on the site of the WHO, until September 8, 2019, your point of view on the subject.

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To find out more:

• See notably: heales.org, sens.org, longevityalliance.org and longecity.org

 

 

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.

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

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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.

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

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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?

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For more information:

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

 

 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.

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

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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.

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

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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.

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For more information:

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

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

 

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.

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

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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.

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

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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.

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For more information:

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

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

 

 

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).

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Theme of the month: deathism, thanatophilia, dolorism

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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.

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

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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.

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For more information:

• heales.org, sens.org, longevityalliance.org and longecity.org
• photo (La Catrina)