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

Theme of the month: Secrets of longevity of blue zones 

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

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

The 5 Blue Zones identified in the world

Sardinia, Italy

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

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

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

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

Okinawa, Japan

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

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

Nicoya, Costa Rica

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

Loma Linda, USA

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

Ikaria, Greece

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

Common characteristics of regions where people live better and longer

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

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

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

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

A very strong social bond

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

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

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

By way of conclusion

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

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

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

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

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

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

For more information:

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

The law is already strict on rapamycin and metformin, requiring a prescription. In comparison, alcohol and tobacco do not require a prescription or medical supervision. Smoking has no health benefits and dramatically reduces life span, accelerating all diseases. While smoking causes cancer, rapamycin prevents it, including smoke-induced lung cancer. Is it then paradoxical that alcohol and tobacco are sold without prescription, while rapamycin and metformin are not. 

Blagosklonny M. V. The goal of geoscience is life extension. Oncotarget. 02 February 2021; 12: 131-144

Theme of the month: Fertility, longevity & menopause

While men are fertile every day, women’s fertility is cyclical. In fact, most girls are born with a certain stock of oocytes from birth, and even a little before. This stock varies between 300,000 and 500,000, of which an average of 400 will actually mature. From puberty onwards, an oocyte is released at each cycle and then eliminated by menstruation when there is no fertilization and over the years, this stock of oocytes decreases. 

And when they’re gone… they’re gone… It marks the end of a woman’s fertility cycle and the arrival of menopause!

Nature is such that, spontaneously, around the age of 50, a woman’s body undergoes a major hormonal change. The health consequences attributed to this change are multiple and variable, both in frequency and in severity. Symptoms include climacteric disorders (hot flashes, chills, feelings of discomfort and dizziness, etc.), mood and sexual disorders (decreased libido, pain during sexual intercourse, vaginitis, etc.), as well as an increased risk of cardiovascular disease and osteoporosis.

When the ovaries quit …

However, for some women, menopause strikes very early. Even before blowing out 40 candles, their lives are turned upside down. A report published on the American website Health explains the 5 reasons why some women are subject to early menopause. Among the factors influencing the age of menopause, there is the genetic factor. In 20% of the cases, a woman who went through menopause very early was not the only one in her family to suffer from this problem. Certain treatments such as chemotherapy and radiotherapy can also affect the genetic material of ovarian cells. But not only that, smoking and being overweight can also be responsible. Several studies state that on average, menopause occurs 2 years earlier in smokers. On the other hand, an overall improvement in diet, hygiene and quality of life in Western countries has put off the average age of menopause.

And among the animals?

Menopause seems to be unique to women… and to cetaceans. This early cessation of reproduction is rare in the animal world. On Earth, only women and four other animal species (the beluga, the narwhal, the killer whale and the pilot whale) experience menopause, a phenomenon among mammals that intrigues scientists. For example, female orcas can expect to live to over 90 years of age, but astonishingly they reach menopause between the ages of 30 and 40. 

But why should a female stop reproducing before the end of her life? This physiological cessation is often described as an evolutionary paradox, as it appears that females derive no benefit from ending their reproductive careers well before death. In a recent study published in Scientific Reports, conducted by researchers from the University of Exeter (UK) and the Center for Whale Research (USA), Dr. Samuel Ellis explains that « For menopause to make sense in evolutionary terms, a species needs both a reason to stop reproducing and a reason to live afterwards”.

The British researcher suggests the « grandmother effect » as an explanation. This hypothesis had been formulated by the anthropologist Kristen Hawkes and her colleagues to understand why menopause occurred during the evolution of humanity. Menopause would have been selected by natural evolution to allow females of very sociable species with a long life expectancy to devote themselves to their direct offspring and those of their children without running the risk of dying during a late pregnancy. After a few generations, a post-menopausal female will therefore have passed on her genes to more offspring than a female who has continued to give birth.

In tribes of hunter-gatherers, it has been found that the chances of survival of the young until the age of reproduction, is positively correlated to the presence of one or two of their grandmothers, certainly because they relieve the mothers in the burdens of child-rearing.

Inmost animals, as in our pets (dogs, cats, mares, cows…), we observe that over the years, the cycle becomes more irregular, that fertility decreases and health concerns can appear because of the drop in sexual hormones, but we cannot call this a real menopause.

Paradoxically, this phenomenon does not exist in any primate. Our closest cousins can become pregnant until the very end of their lives because their reproductive organs slow down with the rest of their bodies. Chimpanzees can remain reproductively viable for more of their lifespan than women. Although research published in 2011 on captive chimpanzees indicates that females go through menopause in their final years.

More surprisingly, in elephants we observe this « grandmother effect » which may explain the usefulness of menopause. However, the females can reproduce until the end of their lives. Scientists do not yet know why cetaceans have a menopause and elephants do not. More studies are needed to solve the mystery…

Birds do not experience menopause either. Some can remain fertile for a very long time. Wisdom, a female Laysan albatross defies nature. The oldest wild bird in the world had a chick at the age of 70! 

Pregnancy after 50? Is it possible to reverse menopause? 

Menopause can be considered either as a natural part of aging or as a pathology that needs to be treated.

It is often said that pregnancy after menopause is impossible. However in 2016, scientists at the Fertility Clinic in Athens managed to reverse the menopause process in a 45-year-old woman even though she had been menopausal for 5 years! 

The scientific team injected the ovaries of about 30 menopausal women with platelet-rich plasma (PRP). It is widely used to speed up the repair of damaged bones and muscles. The women who received the PRP treatment were all between 45 and 49 years old and had not had a period for several months. Six months after receiving a PRP injection, the 45-year-old woman noticed her period returning. The newly released eggs can be collected and fertilized in vitro. This offers a new window of hope for women suffering from early menopause.

In 2020, Dr. Konstantinos Pantos and his scientific teams obtained even more astonishing results: menopausal women gave birth after a PRP injection! Their fertility is said to have been restored thanks to the PRP treatment. Among the 30 menopausal volunteers, four became pregnant and three had children.

Cryopreservation to delay menopause by 20 years! 

This is at least what specialists in in vitro fertilization in Great Britain affirm. Their method has already been tested on nine women. The procedure consisted of taking ovarian tissue which is then frozen to be preserved. Later on as they enter menopause, the frozen tissue can be defrosted and transplanted back into the body to restore declining hormone levels. 

However, experts believe that it is possible to delay the onset of menopause by up to 20 years, but this depends on the age at which the tissue is removed and when it is put back in. For example, tissue taken from a 25-year-old woman could delay menopause by 20 years, while tissue taken from a 40-year-old could delay its onset by only five years.

Conversely, some beauty products bring forward the age of menopause…

According to Dr. Amber Cooper and her team (United States), exposure to chemical molecules, contained in particular in beauty products, can advance the age of menopause by 4 years. Between 1999 and 2008, they conducted blood and urine tests on 31,500 women to check for the presence of chemicals. The researchers found that women with high levels of chemicals in their bodies went through menopause 1.9 to 3.8 years earlier than women with lower levels.

The value  of rodents in the fundamental understanding of key elements in the reproductive and aging processes… 

We wrote earlier that only a few animals experience menopause. However, rats (and mice), at least in the laboratory, gradually cease to be fertile well before their maximum lifespan. Indeed, a rat can live more than three years, but its fertility decreases sharply after 10 months.

As we have seen, the effect of platelet-rich plasma (PRP) has had a positive effect in postmenopausal women in Greece.

In 2018, scientific teams wanted to evaluate the effect of PRP on ovarian structures and function in cyclophosphamide (Cy)-induced ovarian failure in female rats using a stereological method. The researchers concluded that it appears that PRP has a protective effect on ovarian failure in the infertile female rat model.

Rats and mice are imperfect but extremely useful models to better understand and combat the mechanisms of aging. However, to be certain of the effectiveness of a treatment, the maximum lifespan with or without treatment must be compared. This can take a long time since a rat can live more than 3 years. 

By examining the fertility of rats with anti-aging treatments, the information in the laboratory can be obtained much faster. An « ordinary » laboratory rat is 6 months old when experiments begin. After only 4 months of treatment, it will be possible to see if treated rats, compared to control rats, remain more fertile and therefore age less.

It should be noted that longevity experiments are done with a much more pleasant treatment of the animals than the life of sewer rats. This can be explained by the demanding protective legislation and because the goal is to make them live longer, good treatment favors it.

The (relatively) good news of the month:

 The fight against Covid through vaccination is making progress  

To speak of good news about this disease is very relative. There are nearly 3 million deaths recorded. New mutations are appearing more and more. The fine declarations concerning the vaccine, a common good of humanity, have been followed by little effect. Collaboration across financial, social and political barriers is difficult. Finally, populations are exhausted by restrictive measures.
But all is not bleak. By the first quarter of 2021, a big year after the pandemic broke out, more than 100 million people worldwide will have been vaccinated. About 10 vaccines are now being administered worldwide. The vaccines seem to be effective against the different variants of the disease.

As the elderly are the first victims, they are also very often the first to be vaccinated. Never in the history of mankind have we been so concerned about the weakest people in society and about research on this subject.  This is progress for all of humanity. Finally, the realization that Covid is just one of the many age-related diseases is gradually growing. And research to end Covid is sometimes extended to research against other age-related conditions.

For more information:

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

…will we be able to live forever remains an unanswered question; turning a hundred years old into the new sixty – that is significantly extending human lifespan – has changed from a question of « if » to a matter of « when ». Peter Diamandis, entrepreneur, engineer, futurist. Page 179. The Future Is Faster Than You Think.

Theme of the month: Longevity, amortality, transhumanism, technoprogressism

It is one of humanity’s oldest dreams, health without any time limit. We all wish each other this in the New Year. Good health. We know more and more about why and how aging occurs. But we still cannot control senescence.

Not all those who wish to go beyond our biological limits, beyond 100 years of life, will define themselves as transhumanists. On the other hand, almost all transhumanists will describe themselves as longevitists.

What is longevitism?

It is the search for a much longer life, beyond what is possible today, thanks to advances in science and medicine.

Longevitism arouses both attraction and opposition. The opposition isoften motivated by the fear of false hopes, the fear of living longer but in poor health and the fear of therapies only for the rich. 

Longevitists want research for a healthy life, based on serious scientific evidence and are generally attentive to broad accessibility.

Their research may be moderate, aimed at and only a few more years of good health. It can be strong, aiming for a life of well over 120 years.

So the goal of these therapies is to strongly reduce or even eliminate the mechanisms of senescence. The most optimistic will aim at what is called « biological immortality« , the absence of any aging mechanism. The term « amortality » is also used.

What is transhumanism?

Let’s take Wikipedia’s definition: it is a philosophical movement that advocates for the transformation of the human condition by developing and making widely available sophisticated technologies able to greatly modify or enhance human intellect and physiology.

The word transhumanism sometimes frightens people because it evokes the appealof dangerous, dehumanizing technologies. The vast majority of transhumanists are aware of the dangers linked to technical progress. They actively wish for technologies to reduce risks, especially the so-called « existential » ones, to increase resilience and thus the quality and duration of life.

The improvements that transhumanists aim for can be physical: higher, stronger, further, more adapted to the environment. It can be related to the sense organs (better sight, smell, new sensory capacities…). The improvements aimed at can also be related to intellectual capacities. The goal is then to allow more intelligence, more capacity for empathy, compassion, happiness …

But the improvement most often envisaged by transhumanists is that of the improvement of life expectancy, thus the objective of longevitists. This is the necessary, but not sufficient condition for all other increases, for all human rights. Without sustainable life, there are no rights, no possibilities.

What is technoprogressism?

Technoprogressism is a transhumanism for which the idea of linking technological and social progress is central. When we look at the history of humanity, we see that technological progress has largely contributed to social progress and vice versa. But this is not automatic. Technoprogressists will insist on accessibility to technological progress for all those who want it. This applies in particular, of course, to health and longevity therapies.

One of the main founders of transhumanism, Briton David Pearce, summarized transhumanism by 3 S’s: Superlongevity, Superintelligence and Super well-being. Technoprogressists sometimes add « Super democracy » or Supersocial.

“Biological » longevity and « computer » longevity.

For most contemporary longevitists, the ultimate goal is a much longer life with an « ordinary » body, not so different from the contemporary body.

This concept of « ordinary body » must be put into perspective. We already accept today many things that would have appeared totally unnatural even to the most erudite two centuries ago. We transfuse blood, we almost all have foreign bodies in our mouths. At the end of our lives, most of us will have gone through a physiological state that does not exist outside of medicine, somewhere between sleep and death. We call it general anesthesia. Millions of humans have been conceived in a test tube. Millions of us also have pacemakers, cochlear implants… In fact, what yesterday was unimaginable transgression is today medicine. And today’s transhumanism could be tomorrow’s medicine.

But for some more radical transhumanists and longevitists, we could go far beyond our biological composition. Man-machine « fusion » could develop, concerning an increasingly large part of the body, creating a cyborg. Further still, one day, human consciousness could become independent of the body, be transferred onto a computer medium. This vision was discussed in a letter in 2012. It remains today totally hypothetical within a reasonable timeframe. For most longevitists, and probably also for most transhumanists, this could only become possible where computers reproduce biological processes as well as or even better than the processes themselves.  Where the virtual copy would be better than the original. Like a beautiful film can be more beautiful than reality. Like a game can be more enjoyable than the situation that gave birth to it.

This requires nanotechnology and computer efficiency far beyond current capabilities. Above all, it implies being able to understand and replicate the neural mechanisms of what is often defined as « the most complex object in the known Universe« .

Longevity, transhumanism, artificial intelligence

The IT of the near future is above all the development of an increasingly strong artificial intelligence, developed to facilitate human interests. Longevitists, transhumanists or not, hope, and try, to implement computing processes allowing better and faster research. An acceleration of discoveries for health, longevity and resilience also requires massive data that is easilyaccessible and well organized.

Using research capabilities primarily for these purposes, rather than for competitive, military or consumer purposes, is likely to reduce the risks associated with artificial intelligence. Making the best « brains », both human and computational, work together for a much longer healthy life will reduce the risks of developing intelligence that is far removed from human beings.

This is important because the risks of an artificial intelligence « turning radically wrong » are considered high by many. Among those who are concerned, there are many transhumanists, including Nick Bostrom, author of a renowned book on the subject.

More human, tomorrow

Longevitists generally focus first on medical progress and everything that contributes to it. Transhumanists, especially technoprogressists, also seek to analyze why this progress is important. They will explain that a much longer life will make it possible to have

– a more peaceful life, with less violence and more caution;

– to love each other more and to stress us less, since we will have more time;

– to be more careful about the biosphere because we will know that we are here for the long term. A sustainable body is not possible without a sustainable planet.

– Less overpopulation, and more attention to children. For it is where life is longest that children are the rarest and that we have the most time to devote to them.

For these and other reasons, the age-old quest for the Fountain of Youth is today a more desirable and reasonable goal than ever. Today, we still have to accept death from old age because we have no choice. Tomorrow we may choose.

This month’s good news: Conference and workshops on February 11, 2021 on animal and human testing for longevity. Support from Heales for two studies testing the lifespan of rats treated with young plasma.

The February 11th conference on the topic « Clarifying whether and to what extent current anti-aging approaches work in mice or people » was a great success with more than 100 participants.

Present were specialists on the subject such as Irina Conboy, Nir Barzilaï, Greg Fahy and Liz Parrish to name but a few. If you wish to discover them all, the conference split up by speaker remains accessible.

A synthesis of the proposals made during the workshops has been produced.

Since the beginning of 2021, the Heales association has been supporting two studies, carried out by Rodolfo Goya in Argentina and Harold Katcher in India, each following the maximum lifespan of rats treated with blood products, in order to verify the beneficial effect on longevity of this type of treatment.

If significant longevity results are not achieved, this will « close a door ». If important longevity results are established, this will be extremely important news. The conviction of most researchers and the association is that the first hypothesis is the right one. But we would love to be proved wrong!

Find out more:

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

It would be more useful to find out how to make our genome permanently worry-free rather than looking for palliative solutions.

Some ethics specialists believe that they are alone on what they believe to be the right path to progress! They want the slow road that will leave billions of deaths behind because of the lack of preventive/curative care that genome modifications would have allowed.

This vision exasperates me because patients need concrete solutions, not moral bullshit.

Arnaud D. Longevity activist, private email in November 2020.

Theme of the month: Clinical Testing and Longevity

Clinical Trials 

Clinical trials are an essential phase in the development of new drugs. Halfway between research in the laboratory, on cultured cells or animals (rodents, monkeys…), and patient care, this long process takes place in several phases and ensures that the benefits outweigh any risks. It is an indispensable element in the elaboration of big data for health and longevity.

In particular, clinical trials make it possible to determine the populations for whom the drug is most effective and the optimal conditions of use (route of administration, concentration, dosage, etc.). There are three phases in these clinical trials, necessary before the molecule can be authorized for sale as a drug; plus a fourth phase after the product is marketed.

Phase 1, evaluation of the toxicity of the molecule

A Phase 1 clinical trial is the very first use of a new molecule in humans. It may be remunerated. The molecule is tested over a short period of time, from a few days to a few months and on a small number of people, no more than a few dozen.

The objective of the phase 1 trial is to carry out a short-term assessment of the safety of the product’s use, i.e. its possible toxicity, its short-term evolution in the body and an initial pharmacokinetic profile.

In France, the National Agency for the Safety of Medicines (ANSM) states that in this type of first administration trial, « the first dose of the new active substance administered must not cause any detectable short-term toxic effects ». According to Leem (French association of drug companies), 30% of products tested fail to pass this first phase.

Phase 2, efficacy and optimal dosage studied

Once toxicity has been studied, it is the efficacy of the product that is evaluated in phase 2 trials. This type of trial is carried out on small homogeneous groups of 10 to 40 patients with the targeted disease, over a period ranging from a few months to 2 years. The aim is to determine the most appropriate dosage, the smallest effective dose for a given pathology, and to optimize the pharmaceutical form of the product. Only one third of products tested would pass Phase 1 and 2 trials.

Phase 3, the study of the benefit/risk ratio of the drug candidate

This time, the drug candidate is tested on a large sample of patients (at least several hundred), often in international studies.  This involves comparing the drug in development to a placebo (a drug with no therapeutic effect) or to another proven drug. Ideally, this phase should be carried out with randomly selected groups. The objective is to prove efficacy and to evaluate the efficacy/tolerance and benefit/risk ratios of the molecule. This step should also allow the demonstration of possible interactions with any other simultaneous medication.

It is only after these validation steps for the molecule that the drug can eventually obtain marketing authorization (MA). Between 70% and 90% of drugs entering phase 3 are retained for a marketing authorization application.

Phase 4, long-term post-marketing follow-up

This additional step is a follow-up phase of the drug now on the market. Trials are carried out throughout the marketing of the drug and allow to deepen the knowledge of the product in real conditions of use and to detect rarer adverse effects that cannot be detected beforehand.

European regulations

The European regulation EU 536/2014 on Clinical Trials (CTR), which came into force in 2019, brings about a major change for European researchers. The main objectives of this important change in legislation are administrative simplification and harmonization at the European level.

Via a central EU portal, only one application (CTA, clinical trial authorization) will have to be submitted per clinical trial by the sponsor from all Member States taking part in the clinical trial. Only one of the Member States will be designated by the sponsor as « Rapporteur Member State » which evaluates the application centrally and then issues a single opinion to the sponsor and the other Member States concerned.

Situation in the United States

The Food and Drugs Administration (FDA), an agency of the U.S. Department of Health and Human Services, protects public health by ensuring the safety, efficacy and security of human and veterinary drugs, vaccines and other biological products for human use, as well as medical devices.

Over the past several decades, the FDA has encouraged registration practices that would lead to clinical trials that better reflect the population most likely to use the drug if it is approved, primarily by broadening the eligibility criteria. Despite these efforts, difficulties in participating in clinical trials remain, and certain groups continue to be under-represented in many clinical trials, particularly older people.

It should be noted that the U.S. National Library of Medicine’s Clinical Trials site is the official reference for reported clinical trials occurring anywhere in the world.

Ethics Committees

The notion of protection of persons in research practices appeared in the 1930s. After the Second World War, following the atrocious experiments carried out by Nazi doctors and Japanese war criminals, international awareness of the ethics of human experimentation for the protection of individuals began to emerge.

In 1947, the Nuremberg International Tribunal defined a code made up of ten rules, universally known as the « Nuremberg Code« . This Code « recognizes » that experimentation on humans « for the good of society » is permissible and stipulates that « the voluntary consent of the human subject is absolutely essential ». This was followed in 1949 by the International Code of Medical Ethics and in 1964 by the Declaration of Helsinki.

Most countries where clinical research is conducted currently have their own ethics committees, as do the countries of the European Community and the United States. Unfortunately, ethical approvals are often slow and still differ even within the European Union depending on the country (and sometimes even regionally). As a consequence, even in the time of Covid, some research is still considerably slowed down.

Eroom’s law

Eroom’s « law » is the observation that drug discovery becomes slower and more expensive over time, despite technological improvements, a trend first observed in the 1980s.

The cost of developing a new drug roughly doubles every nine years (adjusted for inflation). The current cost of developing a drug based on a new substance is estimated at one billion dollars! To contrast this with the exponential progress of other forms of technology over time, this conjecture has been deliberately called Moore’s Law in reverse.

Self experiments

The famous geneticist George Church didn’t want to wait for the results of the clinical trials. In what appears to be the first « citizen science » vaccine initiative, Preston Estep and at least 20 other researchers, technologists and science enthusiasts, many of whom are linked to Harvard University and MIT, have volunteered as « lab rats ».

To develop a vaccine, the group, called the Rapid Deployment Vaccine Collaborative, or Radvac, studied reports of vaccines against SARS and MERS, two other diseases caused by coronaviruses. The goal is to find « a simple formula that you could make with readily available materials, » says Estep. The vaccine, administered nasally, could create what is called mucosal immunity, that is to say immune cells found in airway tissues. This local immunity could be an important defence against SARS-CoV-2. But unlike antibodies that appear in the blood, where they are easily detected, signs of mucosal immunity may require a biopsy to be identified.

Clinical trials. How to advance medicine. Consent, a condition that is sometimes somewhat fictitious.

Without clinical trials: no new therapeutic methods, no new drugs. Every year, thousands of citizens engage in clinical trials to test new drugs.

Clinical trials must be conducted under the direction and supervision of a physician who must clearly inform the volunteer and obtain « informed » consent about the purpose of the research, its methodology, expected benefits, foreseeable constraints and risks, and the right to refuse to participate in research. Anyone who has consented to participate in research is free to withdraw consent at any time, and thus stop participating in the research.

The law makes it clear that the interests of those who participate in clinical research always outweigh the interests of science and society. In this area, we have moved from one extreme to the other, from abuses of human experimentation to provisions where even those who accept to take informed risks for the common good are not allowed to do so. Moreover, this extremely cumbersome legislation does not harm certain private interests, on the contrary. Only the big pharmaceutical companies are able to carry out the tests and to remunerate expensive and time-consuming legal and administrative staff. Small competitors are therefore eliminated (or absorbed), regardless of the value of their ideas.

Finally, it should be noted that for seriously ill people in hospital who are offered an experimental treatment, no matter what happens, informed consent is best summed up as « We are offering you a treatment for which we think you have a better chance of survival (or improvement). You are free to take that chance or increase your risk of dying ». Since the patient will still remain in the same facility if he or she refuses, even if the doctor is acting in perfect good faith, this limits the « free » character.

A question of patents and financial interests (Belgian example)

In 2018, 162 patent applications for drugs and/or vaccines were filed in Belgium (+30% compared to 2017), 507 new clinical studies were initiated and 1,399 drug studies were conducted. Last year, nearly 3.6 billion euros were invested in research in Belgium by (bio)pharmaceutical companies.

Three out of four clinical trials (77%) are organized and financed by the (bio)pharmaceutical companies themselves. The remaining 23% are carried out at the initiative of the academic or public sector. This proportion of private funding is one of the highest in Europe. Direct public investment in health is low. There is a high level of tax and other support for the privatization of research.

And the consequences for longevity research?

Measuring the impact of therapies for the elderly is complex. Obtaining their « informed » consent is often impossible, especially in the fight against neurodegenerative diseases.

Conducting clinical tests to fight against aging will be difficult, especially because deaths or accidents during clinical tests inspire fears. However, by definition, with or without treatment, mortality and morbidity will be higher in older subjects.

Yet, as we have seen with Covid research, enabling the oldest and most fragile people to live longer can become an almost absolute priority, even at considerable economic cost. Confidence is generally greater when research is carried out by non-profit organizations (public or not), leading to research results that can benefit everyone, without commercial involvement.

There are millions of young, old, and very old men and women who are willing to give informed consent (or who were willing to do so when they were still fully aware) for healthy longevity advances, even if they are not certain to benefit directly. In any case, in the event of experimental treatment, these people will benefit from very detailed follow-up, which will almost always be favorable to their health.

The good news of the month : Progress on Covid-19

In several countries, including France and even more so Belgium, overall mortality in 2020 will unfortunately be higher than in 2019.

Fortunately, at the end of this year, the huge efforts in vaccine research are now making it possible for products to be used no longer in the test phase, but on the general population, with a strong predicted efficacy and few side effects. Of the more than 300 vaccines in development worldwide, three are already being administered to the general population (two in China and one in Russia) and three are approaching this stage for the rest of the world (vaccines from consortia including Pfizer, AstraZeneca and Moderna, respectively).

No doubt, complex discussions will be held about choices, prices or anti-vaccine opposition. To get to where we are today may seem like a long road. However, the epidemic is less than a year old. Never before has a vaccine against a virus of the coronavirus family been made. The development of a new vaccine normally takes years.

A more « incremental » piece of positive news is that thanks to better knowledge of the disease and of therapies, especially in intensive care, mortality has decreased quite slowly but steadily for patients with the disease.

Find out more:

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