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Donations from Didier Coeurnelle enable next phase of Robust Mouse Rejuvenation research program

Longevity Escape Velocity Foundation (LEVF) today welcomes two very generous donations from long-time supporter of longevity research and activism, Didier Coeurnelle.

The first donation is 200,000 euros (approximately 220,000 US dollars). The second donation, of up to another 200,000 euros, is dependent on LEVF receiving matching gifts from other donors from 1st October until the end of the month (October 31st).

These donations enable a key set of pre-study pilots ahead of the next phase of LEVF’s groundbreaking investigations into the effects of combining different damage-repair interventions for middle-aged mice.

RMR1, the first phase of this Robust Mouse Rejuvenation project, has been running since February 2023, and is now nearing completion. Mice in this project have received combinations of up to four different treatments.

Caitlin Lewis, Director of Project Pipeline & Strategy at LEVF, commented: “These donations come at exactly the right time, as we are ready to commence pre-study pilot trials ahead of RMR2. RMR2, which will involve mice receiving combinations of up to six different life-extension treatments, takes into account significant findings from RMR1. These experiments have the potential to achieve record-breaking extension of both healthspan and lifespan of middle-aged mice, and to catapult longevity intervention combinations into the mainstream and into the clinic.”

Didier Coeurnelle commented: “The RMR investigations are poised to transform public understanding of the possibilities of treatments to extend healthspan and lifespan, not only in mice, but in humans. These investigations particularly deserve financial support, from anyone who shares my conviction that treating aging is a profoundly urgent humanitarian task. October 1st is the start of Longevity Month, in which longevity advocates around the world place a special focus on the need for faster progress. I hope my own donations can inspire others to consider how they, too, can best help to accelerate the defeat of aging.”

Aubrey de Grey, President and CSO of LEVF, replied: “This is a wonderfully generous donation from Didier. Via his previous financial support and his tireless advocacy for more than 15 years, Didier has long been a bold champion of the quest to reverse aging. This is by far the largest donation he has made, and affirms our joint belief that now is the time to greatly expand research to target the underlying processes of aging. Anyone else who wishes to make a donation to support RMR or any of the other activities undertaken by LEVF can do so via the donation page on our website, https://www.levf.org/donate.”

About LEVF: Longevity Escape Velocity Foundation is a 501(c)(3) tax-exempt California nonprofit public benefit corporation (EIN 93-2716970). It exists to conduct and inspire research to proactively identify and address the most challenging obstacles on the path to the widespread availability of comprehensively effective treatments to cure and prevent human age-related disease. See https://www.levf.org/.

About RMR: The Robust Mouse Rejuvenation research program is a sequence of large mouse lifespan studies, each involving the administration of various subsets of at least four interventions that have, individually, shown promise in others’ hands in extending mean and maximum mouse lifespan and healthspan. The research focuses on interventions that have shown efficacy when begun only after the mice have reached half their typical life expectancy, and mostly on those that specifically repair some category of accumulating, eventually pathogenic, molecular or cellular damage. See the results of the first phase https://www.levf.org/projects/robust-mouse-rejuvenation-study-1.

About Didier Coeurnelle: Didier Coeurnelle is co-chair of HEALES, the Healthy Life Extension Society, an organization that promotes and supports anti-aging research by raising awareness about technological and medical developments in the field of biogerontology. See https://heales.org/. Didier is also a member of the board of the International Longevity Alliance, https://longevityalliance.org/, and is the author of the highly regarded newsletter “La Mort de Mort” which is published each month in French, English, Spanish, and Dutch, https://heales.org/category/deathofdeath/monthly-newsletter/. He has published two books (in French) about longevity and transhumanism, is a Belgian citizen, and works in Brussels as a senior civil servant.

Heales monthly newsletter. The death of death N°185. September 2024. Muscular system and longevity


And if we manage to lengthen life – even if that’s not the case today – there are so many men and women to love and so many books to read, that three centuries isn’t very long at all. Luc Ferry Philosopher. Interview on Europe 1, April 2016.


This month’s theme: Muscular system and longevity


The aging of the muscular system in humans, also known as sarcopenia, involves a complex interplay of physiological changes that lead to the gradual loss of muscle mass, strength, and function. 

Individual muscle fibers, especially type II (fast-twitch) fibers, shrink and reduce in number with age. Type II fibers are responsible for quick and powerful movements, so their loss contributes to decreased strength and speed. Overall muscle mass 

declines with age due to the loss of muscle fibers and the reduction in the size of remaining fibers. This process is influenced by hormonal changes, decreased physical activity, and altered protein metabolism. The neuromuscular junction (NMJ), where nerve cells connect with muscle fibers, also deteriorates with age. This degeneration leads to impaired communication between the nervous system and muscles, resulting in reduced muscle function and strength. We also see mitochondrial dysfunction, the energy-producing organelles in cells, become less efficient with age. This dysfunction leads to reduced energy availability for muscle contraction and increased production of reactive oxygen species (ROS), which can damage cellular components. 

Aging affects the balance between muscle protein synthesis and degradation. Levels of anabolic hormones such as growth hormone, testosterone, and insulin-like growth factor 1 (IGF-1) decrease with age. These hormones play crucial roles in muscle maintenance and repair. Chronic low-grade inflammation, often referred to as « inflammaging, » is associated with aging. Pro-inflammatory cytokines can promote muscle catabolism and interfere with muscle repair and regeneration processes. Satellite cells are muscle stem cells that play a key role in muscle repair and regeneration. Their number and function also decline with age, impairing the muscle’s ability to recover from injury and maintain muscle mass. 

Aging is often accompanied by a decrease in physical activity levels, which accelerates muscle loss. Regular exercise, particularly resistance training, can mitigate some of the effects of aging on the muscular system by promoting muscle protein synthesis and improving neuromuscular function.

Sarcopenia

It is defined as the age-related, involuntary loss of skeletal muscle mass and strength. Starting as early as the 4th decade of life, evidence suggests that both skeletal muscle mass and strength decline in a linear fashion, with up to 50% of muscle mass being lost by the 8th decade of life. Since muscle mass accounts for up to 60% of body mass, pathological changes to this metabolically active tissue can have significant consequences for older adults. The strength and functional declines associated with sarcopenia can lead to severe outcomes, including loss of function, disability, and frailty. Additionally, sarcopenia is linked to both acute and chronic disease states, increased insulin resistance, fatigue, falls, and ultimately mortality. Among chronic diseases, sarcopenia is particularly associated with rheumatologic conditions, especially rheumatoid arthritis (RA) in women.

Overall declines in the size and number of skeletal muscle fibers characterize the physiological and morphological changes in skeletal muscle with advancing age. Additionally, there is a significant infiltration of fibrous and adipose tissue into the skeletal muscle. Satellite cells, which are skeletal muscle precursor cells residing in a quiescent state associated with myofibrils, also undergo important age-related changes. These satellite cells are activated to initiate skeletal muscle repair and regeneration in response to the stress of heavy muscle use, such as weight-bearing activities, or traumatic events, such as injury. 

Molecular Mechanisms of Muscle Aging

In older individuals, the balance between protein synthesis and breakdown may be disrupted, leading to increased muscle catabolism and a reduction in skeletal muscle mass. These changes are characteristic of old age and frailty. Frailty has been reported to exacerbate aging-related disruptions in protein metabolism. A lack of dietary protein is a potential factor contributing to decreased muscle protein synthesis in the elderly. The dietary protein intake of old people is often below the recommended daily allowance for both men and women. 

Gender Differences in Muscle Aging

Higher rates of muscle mass loss during aging have been reported in males compared to females and a higher prevalence of sarcopenia has been observed in males compared to females. Some studies have identified sex-specific markers for sarcopenia. One electron microscopy study measured mitochondrial content and found that intermyofibrillar mitochondrial size primarily decreased in older females, not in older males. Moreover, in the FITAAL study, it was found that intramuscular (acetyl) carnitine levels decreased with age in females but not in males. These findings suggest that during aging, females experience more changes in mitochondrial content and function compared to males. Additionally, the composition of the plasma proteome is known to change with aging, and interestingly, a large human study found that these age-associated changes were highly sex-specific.

Therapies

A study investigated the long-term effects of muscle hypertrophy, achieved through the overexpression of human follistatin (a myostatin antagonist), on neuromuscular integrity in C57BL/6J mice aged 24 to 27 months. Follistatin was delivered via self-complementary adeno-associated virus, resulting in significant improvements in muscle weight and torque production. The treatment enhanced neuromuscular junction innervation and transmission, although it did not affect age-related motor unit losses. These findings show that follistatin-induced muscle hypertrophy not only boosts muscle weight and torque but also mitigates age-related neuromuscular junction degeneration in mice.

The team of George Church along with Liz Parish from Bioviva Science demonstrated that using CMV as a gene therapy vector allows for monthly inhaled or intraperitoneal treatment for aging-related decline. In a murine model, exogenous telomerase reverse transcriptase (TERT) or follistatin (FST) genes were delivered safely and effectively. This treatment significantly improved aging biomarkers and increased mouse lifespan by up to 41% without raising cancer risk, offering a promising approach to address the global rise in aging-related diseases. As seen in other studies, FST-treated mice showed increased body mass, correlating with muscle mass gains. FST enhances mitochondrial biogenesis, energy metabolism, cellular respiration, and thermogenesis, promoting the browning of white adipose tissue. This regimen required monthly administration to maintain continuous effects, which could be beneficial for episodic treatment needs, reducing long-term adverse reaction risks.


The good news of the month: Government-funded research aims to Replace Aging Brain with Lab-Grown Tissue


Jean Hébert (A genetics and neuroscience professor at the Albert Einstein School of Medicine in The Bronx), recently hired by the US Advanced Projects Agency for Health (ARPA-H), spearheads a groundbreaking anti-aging approach by replacing parts of the human brain with cloned tissues. His research focuses on progressively replacing brain parts with young, lab-grown tissues, allowing the brain to adapt and maintain its functions. 

This could preserve memories and key identity facets, leading to significant advancements in anti-aging treatments. His innovative work, if successful, could lead to breakthroughs in reversing brain aging and enhancing human longevity.


For more information

Heales monthly newsletter. The death of death N° 184. August 2024. Planaria


In my ideal world….maybe 50% of 7.8 billion people would have online access to education and information and would collectively work (each contributing in their own way like mining or gamers or up to researchers and decision-makers and with a limitless supply of money) to address aging or the degeneration known as aging that leads to all chronic diseases….that’s not the world we live in. Martin O’Dea in 2021, CEO Longevity Summit Dublin.


This month’s theme: Planaria


Introduction

When stem cells divide for healing wounds, reproduction, or growth, they typically show signs of aging. This aging process results in stem cells losing their ability to divide, thus becoming less capable of replacing exhausted specialized cells in our tissues. A clear example of this effect is seen in human aging skin. However, planarian worms and their stem cells somehow bypass this aging process, allowing their cells to continue dividing indefinitely. One key factor in cellular aging is related to telomere length. For normal growth and function, cells in our bodies must continually divide to replace worn-out or damaged cells. Planarian worms maintain the ends of their chromosomes in adult stem cells, theoretically granting them immortality.

Planaria are capable of profound feats of regeneration fueled by a population of adult stem cells called neoblasts. These cells are capable of indefinite self-renewal that has underpinned the evolution of animals that reproduce only by fission, having disposed of the germline, and must therefore be somatically immortal and avoid the aging process. How they do this is only now starting to be understood. A study suggests that the evidence so far supports the hypothesis that the lack of aging is an emergent property of both being highly regenerative and the evolution of highly effective mechanisms for ensuring genome stability in the neoblast stem cell population

Planaria. Common genes with humans, how many?

Planaria and humans share a surprising amount of genetic material despite their differences. Approximately 80% of the genes in planaria have homologs in the human genome. This significant overlap includes genes involved in fundamental biological processes, such as those related to stem cell function and regeneration. This genetic similarity makes Planaria an important model organism for studying biological processes relevant to humans​.

Scientists hope that understanding how these cells activate and differentiate could one day lead to methods for regenerating human tissues. One gene, called piwi in planaria and hiwi in humans, is expressed in both species’ stem cells and is likely involved in regeneration. In planaria, piwi plays a crucial role in producing new, functional stem cells. In humans, the hiwi gene is expressed in reproductive cells and some stem cells, such as those responsible for generating new blood cells. There is hope that studying this gene could be useful to trigger human stem cells into regenerative action.

Almost Immortal Planaria

Many people first encounter planaria, tiny flatworms with remarkable regenerative abilities, during biology class when they cut one up. Planaria, found in freshwater, marine environments, and on plants worldwide, can be sliced into hundreds of pieces, each growing into a completely new flatworm. This extraordinary ability allows planaria to reproduce asexually, effectively cloning themselves. Scientists have discovered that planaria are filled with cells akin to stem cells, which are always ready to transform into any specific type of cell needed for tissue regeneration. This capability closely mirrors that of embryonic stem cells in humans and other vertebrates, making planaria fascinating subjects for scientific study. Their simple bodies and limited tissue types make them relatively easy to research. Remarkably, the stem cell-like cells in planaria are distributed throughout their bodies in large numbers, which contributes to their incredible regenerative powers. 

Planarian regeneration is notable for its dramatic extent, rapid speed, and the underlying mechanisms that enable it. Not only can each piece of a cut-up planarian regenerate into a new flatworm, but this process occurs quickly, taking just a week or two for each fragment to become a miniature version of the original worm. 

During regeneration, planaria perform an impressive feat: for instance, a tail regenerating a head might lack the ability to eat, or a head without a gut can’t digest food. Planaria solve this by consuming themselves—cells in the tail self-destruct to provide the energy needed for regeneration. As the head regrows, the tail shrinks to a size proportionate to the new head. Once the planarian is fully regenerated, it resumes feeding and returns to normal size. Understanding how planaria achieve this proportion adjustment during regeneration is one of the many mysteries scientists are eager to solve. When a planarian loses a part of its body, a regeneration blastema—a cluster of embryonic-like cells—forms at the wound site. These cells, rich in stem cells, can develop into various cell types needed to replace the lost body part. 

Planarians do age, from the loss of fertility to a reduction in muscle mass and mobility. However, when elder planarians regenerate tissues, the newly formed parts show no signs of aging. It’s as if they completely turn back the clock. Understanding and « copying » what they do could lead to ways of slowing or even reversing age-related conditions in humans.

Michael Levin Study

The study of this American developmental and synthetic biologist provides a comprehensive model connecting bioelectric signals with molecular feedback loops during early anterior-posterior (AP) axis establishment in planaria. 

Bioelectric signals influence early polarity decisions in regeneration, and manipulating these signals can lead to significant anatomical outcomes, such as the formation of double-headed planaria. In other words, as strange as it seems, at least in some circumstances, bioelectric signals can create a morphology that would not exist in a « normal » environment. 

Understanding the interplay between bioelectric signals and molecular pathways could lead to improved control over regeneration and morphogenesis. Given that many ion transporter modulators are already clinically approved, this research holds promise for applications in regenerative medicine. 

This study underscores the importance of bioelectric signals in regeneration, a field of science largely unexplored. It is one of the many avenues for regeneration and rejuvenation of human beings. We need more scientists and more investment in all research, who could one day make possible longer and healthier lives for billions of people.


The good news of the month: An antibody extends life span in mice by 25%


The mice received a therapy against IL-11, a pro-inflammatory cytokine. This cytokine has a negative effect on the lifespan of mice and also on humans.

The scientists from London who published in Nature explain that the mice that received the antibody looked more active, and leaner, with better coat, vision and hearing, and better walking ability.


For more information

Heales Monthly Newsletter. The death of death N°183. July 2024. Recent positive evolutions of life expectancy in the world


Death makes me very angry. Premature death makes me angrier still. Larry Ellison, founder of Oracle (source)


This month’s theme: Recent positive evolutions of life expectancy in the world


Introduction

From 1946 until 2019, at the World level, it could be said that each year was the best time ever to be alive, at least concerning the duration of it. This almost secular trend was broken in 2020, 2021, and maybe 2022. The Covid period it marked the first time since the Second World War with a global decrease in life expectancy. A previous letter exposed the situation known one year ago.

Since 2022, the situation considerably improved especially in Europe and in the USA. We can reasonably think that today is again the best time ever to be alive. However, we have to wait for more data to be sure …. and to hope for the future.

About data concerning life expectancy

What is life expectancy? It is the average period that a person may expect to live. There are various ways to calculate it. Period life expectancy at birth is life expectancy since birth calculated for a given year (or sometimes another period). It is based on the probability of death of each person during this year. So, it uses mortality rates from a single year and assumes that those rates apply throughout the remainder of a person’s life. This means that when there is a high mortality during a given year, the calculated life expectancy will decrease strongly. This means also that any positive or negative future changes to mortality rates are not taken into account.

Life expectancy approached in this letter is measured for countries and by sex. Data concerning life expectancy in good health, life expectancy for various groups, levels of income … are interesting, but not available worldwide and generally less reliable.

We could think that life expectancy is something very easy to measure. The date of birth and the date of death of a person is basic information known precisely to almost everyone. However, there are problems, namely:

  • Especially in countries with poor administrative organization, births, and deaths can be not registered; Since in general, a high life expectancy is seen as positive, there can be a trend to exaggerate longevity, especially for very old people. 
  • People migrating can influence: what if a person is born in one country and dies in another, what about foreigners dying, will they be considered for life expectancy in their country of nationality or residence… ?
  • And the biggest difficulty: the slow transmission of data.

Official data are slow to be available. In 2024, available real-life expectancy data still often predates the Covid-times. More recent data are often contradictory. Data you find online for 2022 and 2023 are often actually prospects. For example, data for Kyrgyzstan and Bhutan. This is in a way fascinating and depressing. Not only do we not yet know how to stop aging, we don’t even know how to calculate it globally. 

In most countries, an official institution gives information about life expectancy. But to compare at the world level, we have to rely on data coming from international institutions, especially the World Health Organization. The Wikipedia page on life expectancy gives data from 2023 from the United Nations, from 2022 for the World Bank Group and the OECD, and from 2019 for the World Health Organization.

Other good sources are:

Those sources are mostly based on official data, often from the UN.

World analysis of life expectancy by the WHO

The rise in life expectancy was temporarily halted during 2020 and 2021 due to the impact of the COVID-19 pandemic. At the height of the pandemic, global life expectancy at birth fell to 70.9 years, down from 72.6 in 2019. However, since 2022, life expectancy has returned to levels observed before the emergence of COVID-19 in nearly all countries and regions. This recovery marks a return to the positive trend in longevity seen over the past decades.

Globally, life expectancy at birth reached 73.3 years in 2024, an increase of 8.4 years since 1995. Further reductions in mortality are projected to result in an average longevity of around 77.4 years globally by 2054. According to the WHO projections, more than half of all deaths worldwide will occur at age 80 or higher by the late 2050s, compared to 17 percent in 1995. 

European situation

In Europe, we live now longer than before the COVID-19 period. In 2023, life expectancy at birth in the EU was 81.5 years, up 0.9 years from 2022 and 0.2 years from the pre-pandemic level in 2019, according to data released by Eurostat on May 3.

This is a very positive evolution and the best progress in one year since many years. This means also that the negative consequences of COVID-19 are finally behind us.

The highest expectancy was recorded in Spain (84.0 years), Italy (83.8 years), and Malta (83.6 years). On the opposite side, the lowest life expectancy at birth is in Bulgaria (75.8 years), Latvia (75.9), and Romania (76.6). In France and Belgium, life expectancy is respectively of 82,7 and 82,3 years.

For Europe, very recent statistics are available. Mortality levels observed by EuroMOMO have been lower than expected throughout spring 2024. So, the positive situation seems to continue.

The situation in North America

US life expectancy began to stagnate specifically in 2012, before declining from 2015 onwards. The impact of COVID-19 in the US was worse than in Europe. This meant that life expectancy in 2021 dropped to the level it was 20 years before, reaching its lowest point since 1996.

Happily, the situation has radically improved in the last few years. In 2022, by gaining 1.1 years between 2021 and 2022, life expectancy at birth reached 77.5 years.  In 2023, life expectancy is reported as 79.74 years for both sexes, 82.23 years for women, and 77.27 years for men. The current outlook is much better than at the end of the COVID-19 period, especially for women.

In 2023, the Mexican national statistical agency INEGI reported that the total life expectancy in Mexico was 75.3 years, surpassing the pre-COVID 2019 level by 0.5 years. INEGI forecasts that in 2024, life expectancy in Mexico will continue to rise, predicting it to reach 75.5 years. Detailed life expectancy data for each Mexican state can be found on this Wikipedia page.

In 2022, for the third consecutive year, life expectancy in Canada had declined, marking a historic and concerning trend with a more significant decline among females.

The year 2020 marked a breaking point in Canada’s increasing life expectancy. However, Quebec rebounded quickly, reaching 83 years in 2021, surpassing pre-pandemic levels. Elsewhere in Canada, the decline persisted according to the latest data.

Asia

It is strangely difficult to have precise information about life expectancy in the two largest countries of the world. 

In India, the life expectancy for both sexes in 2023 is 72.03 years, with females at 73.65 years and males at 70.52 years. This is supposed to be more than in 2019, but these data are not without questions.

In China, according to data released by the National Health Commission, life expectancy at birth increased from 77.9 years in 2020 to 78.2 years in 2021. By 2023, for some information, life expectancy for both sexes reached 78.79 years, with females at 81.52 years and males at 76.18 years. However, the COVID situation has a negative peak later than in the other countries and the number of deaths in 2023 was rising 6,6 %.

In Japan, life expectancy has been declining in 2021 and 2022 but is probably rising again.

Hong Kong residents no longer hold the record for the world’s longest life expectancies, having ceded this position to Japan as COVID and overall stress impact local lifespans. In 2022, the average life expectancy for women in Hong Kong was 86.8 years, while their Japanese counterparts were expected to live until 87.1 years, according to the latest statistics released by Hong Kong’s government. Data for 2023 and 2024 has not yet been published.

African analysis of life expectancy by the WHO

Before the pandemic, the African region saw substantial gains in life expectancy, with an increase of 11.2 years since 2000. 

Life expectancy has been rising again since 2022. As of 2023, the African countries with the highest life expectancies are Algeria, Tunisia, and Cape Verde, each with 77 years, followed closely by Mauritius at 76 years.

In contrast, the countries with the lowest life expectancies in Africa are the Central African Republic and Lesotho, both at 55 years, and Nigeria and Chad, both at 54 years. These disparities highlight the ongoing challenges and varying progress in healthcare across the continent.


The good news of the month: Age-reversal trial with old human volunteers


The company Mitrix Bio plans to begin the first age-reversal trial in human volunteers later this year. The study is first aimed at helping astronauts withstand the high-radiation, microgravity conditions of space, which lead to muscle loss and other complications of premature aging. The company will transplant young, bioreactor-grown mitochondria into a group of volunteers in their 70s and 80s to see if the technique reverses aging.

It is positive that Space Research may help for longevity and that with an experiment made with aged well-informed volunteers.


For more information

Heales Monthly Newsletter. The death of death N°182. June 2024.  Longevity and the Digestive System.


((…)) to make ourselves masters and possessors of nature. This is not only to be desired for the invention of an infinite number of artifices, which would enable us to enjoy the fruits of the earth and all the conveniences found therein without any difficulty but principally also for the preservation of health ((…)) if it is possible to find some means that will commonly make men wiser and more skillful than they have hitherto been, I believe that it is in medicine that it must be sought. » René Descartes, philosopher, 1637.


This month’s theme: Longevity and the Digestive System


Introduction

The relationship between longevity and the digestive system is significant, as a healthy gut microbiota, balanced diet, and efficient digestion contribute to overall well-being and lifespan. A diverse gut microbiota supports immune function and reduces chronic inflammation, which is linked to many age-related diseases. Good digestive health prevents conditions like colorectal cancer and ensures efficient nutrient absorption. Additionally, the gut-brain axis shows that a healthy gut can improve mental health, further promoting longevity. Incorporating probiotics and prebiotics can enhance gut health by supporting beneficial bacteria. Thus, maintaining a healthy digestive system through diet, exercise, and stress management is crucial for a longer, healthier life.

Gut Microbiota

Diversity and Balance: A diverse and balanced gut microbiota is crucial for maintaining good health. Studies have shown that people with a wide variety of gut bacteria tend to have a healthier aging process and potentially longer lifespans.

Immune System Interaction: The gut microbiota plays a vital role in the immune system. A healthy gut can help prevent chronic inflammation, which is linked to many age-related diseases.

Research shows that alpha diversity, a measure of microbiota variety, increases with age among normal and successfully aging older adults. This rise in diversity seems to have a positive effect. Beta diversity, which reflects differences in microbial composition between individuals, significantly differs between older and younger adults, and even between the oldest-old and younger-old adults. Although the specific taxonomic composition and functional potential vary across studies, Akkermansia is consistently more abundant in older adults. At the same time, Faecalibacterium, Bacteroidaceae, and Lachnospiraceae are reduced, especially among the oldest-old. Compared to younger adults, older adults exhibit reduced pathways related to carbohydrate metabolism and amino acid synthesis. 

However, the oldest-old individuals show increased short-chain fatty acid production and enhanced pathways related to central metabolism, cellular respiration, and vitamin synthesis. Studies have shown that beta diversity significantly changes across different life stages, continuing to diverge even within older age groups. Oldest-old adults with high alpha diversity have greater temporal stability in their microbiota composition. Lower alpha diversity is associated with decreased cognition in aging and is a marker of metabolic and inflammatory diseases. These findings suggest that Akkermansia may support gut homeostasis and healthy aging by reducing inflammation and the risk of metabolic and cognitive disorders.

A fecal microbiota transplant (FMT), also referred to as a stool transplant, involves transferring fecal bacteria and other microbes from a healthy donor to another person. FMT is a proven treatment for Clostridioides difficile infection (CDI). For recurrent CDI, FMT is more effective than vancomycin alone and may enhance outcomes even after the initial infection.

Probiotics and Prebiotics

Probiotics are live microorganisms that provide health benefits when consumed, often found in fermented foods such as yogurt, kimchi, and sauerkraut. They support gut health by introducing beneficial bacteria to the microbiome and reducing the growth of harmful bacteria by occupying their space. Prebiotics are nutrients that promote the development of beneficial gut bacteria, thereby enhancing overall gut health. The primary prebiotics is microbiota-accessible carbohydrates (MACs), commonly known as dietary fiber. Found in fruits, vegetables, whole grains, legumes, and other plant materials, these complex carbohydrates resist digestion and absorption, allowing them to reach the colon intact and feed gut bacteria.

The gut microbiota influences cellular senescence and skin health through the gut-skin axis by secreting microbial metabolites. Metabolomics can help identify and quantify these metabolites involved in senescence. Novel anti-senescent therapeutics are useful. Probiotics and prebiotics may serve as effective alternatives, given their connection to the microbiome and healthy aging. However, the known effects are limited, and further research on gut composition during senescence is needed to develop immunomodulatory therapies.

Inflammation and Aging

An unhealthy gut can cause a « leaky gut, » leading to systemic inflammation and accelerated aging. 

The human body encounters potentially toxic and infectious substances daily in the gastrointestinal tract (GIT), which bears the greatest load of antigens. The GIT maintains intestinal integrity by permitting beneficial agents to pass while blocking harmful substances. Normally, a healthy intestinal barrier prevents toxic elements from entering the bloodstream. However, factors like stress, an unhealthy diet, excessive alcohol, antibiotics, and drug consumption can disrupt the intestinal microbiota and compromise the homeostasis of the intestinal barrier, leading to increased intestinal permeability. This condition, known as intestinal hyperpermeability, allows harmful agents to pass through the junctions of the intestinal epithelium into the bloodstream, affecting various organs and systems. 

Consequently, leaky gut syndrome and intestinal barrier dysfunction are linked to intestinal diseases such as inflammatory bowel disease and irritable bowel syndrome, as well as extra-intestinal diseases including heart disease, obesity, type 1 diabetes mellitus, and celiac disease. Given the relationship between intestinal permeability and numerous conditions, it is essential to develop effective strategies to prevent or reduce increased intestinal permeability. The impact of dietary nutrients on barrier function is crucial for designing new strategies for patients with leaky gut-related diseases associated with epithelial barrier dysfunction.

Aging of the Digestive System

Age-related changes in gut function have profound effects on the motility of the esophagus, stomach, and colon. Older adults are particularly vulnerable to conditions such as malnutrition, postprandial hypotension, dysphagia, constipation, and fecal incontinence. 

Reduced numbers of nerve cells in the myenteric plexus, crucial for digestive absorption, and degeneration of villi, which reduces the surface area of the small intestine, contribute to impaired nutrient absorption. Furthermore, aging impairs the intestinal immune system, including the mucosal layer of the gastrointestinal tract, leading to a higher incidence and severity of infections among older individuals. Defects in the structure and function of the mucosal defense system, a reduction in the capacity to produce protective immunity, and a rise in the frequency of inflammation and oxidative stress are all linked to aging.

Although it can affect people of all ages, gastroesophageal reflux disease, or GERD, is most frequent in older persons. Heartburn and associated symptoms of reflux disease (GERD) are brought on by stomach acid backing up into the esophagus. Reflux can be favored by eating the improper meals, such as fried and fast food, and by eating late at night. Heartburn can result from taking certain drugs, such as blood pressure medications, which are commonly taken by older persons. Gaining weight as you age increases your likelihood of developing GERD and heartburn.

Colorectal Cancer

Cancers concerning the digestive system are not the most current and well-known cancers. However, all cancers related to the digestive are responsible for about one-third of all cancer deaths​.

Mental Health

The gut-brain axis shows that a healthy gut can positively influence mental health, reducing depression and anxiety, which are linked to longevity. Disruptions in the gut-brain axis affect intestinal motility and secretion, contribute to visceral hypersensitivity, and lead to cellular alterations of the entero-endocrine and immune systems.

Gastrointestinal diseases, such as irritable bowel syndrome, frequently involve psychological comorbidities linked to changes in the gut microbiome. Furthermore, studies have shown that the makeup of the gut flora may have an impact on the brain development of fetuses and newborns. Not surprisingly, food has also been demonstrated to affect gut microbiota’s effect on cognitive performance.

Conclusion

Almost every day of our life, our body absorbs and transforms a big mass of substances, containing non-edible and often even toxic parts. In many aspects, our digestive system is the strongest part of our body. For example, intestinal Epithelial Cells are replaced approximately every 2 to 5 days which is essential for maintaining the integrity and function of the digestive barrier exposed to harsh digestive enzymes and varying pH levels​.

This part of the body can give some ideas to scientists about how to have a more resilient body and better stem cells.


The good news of the month: Repair Biotechnologies developed the Cholesterol Degrading Platform, a safe approach to treating medical conditions that arise due to localized accumulations of excess cholesterol


Repair Biotechnologies has developed LNP-mRNA gene therapy that has shown promising results in preclinical models of atherosclerosis. In the LDLR knockout mouse model, the therapy reduced aortic plaque volume by 17% after six weeks of treatment. Additionally, the APOE knockout mouse model, successfully removed plaque lipids and improved plaque stability. 

The therapy operates by eliminating toxic excess free cholesterol in the liver, restoring liver homeostasis, and generating systemic benefits throughout the body. The company is preparing for a series A funding round to pave the way for its first clinical trial in 2026, targeting the rare genetic condition of homozygous familial hypercholesterolemia. There is potential for fast-track approval, which could lead to off-label use for treating severe atherosclerosis in the broader population.


For more information

Heales Monthly Newsletter. The death of death N°181. May 2024. Our organs do not all age at the same rate


If immortality means perpetuating our own metabolisms, why not? This kind of immortality, whether bionic or technological, is conceivable. Jean-Michel Besnier, French philosopher (translation, source).


This month’s theme: Our organs do not all age at the same rate


Introduction

We begin to age, each of us differently, before our birth. For example, the epigenetic age of male babies is in average higher than that of female babies. When we die of diseases related to old age, some organs may be still relatively « young ».

Different organs in the human body can age at different rates. Aging is a complex process influenced by various factors, including genetics, lifestyle, environmental exposures, and overall health. Some organs may show signs of aging earlier or more prominently than others due to differences in their structure, function, and susceptibility to damage over time as well as specificities of our behavior and habits. 

The skin is often one of the first organs to show visible signs of aging, such as wrinkles and age spots, due to exposure to sunlight and other environmental factors. Similarly, the cardiovascular system may exhibit signs of aging through changes in blood vessel elasticity and function, leading to conditions like hypertension and atherosclerosis. The digestive system will slow down because of the weakening of the muscular contractions. The brain generally exhibits age-related changes such as a decrease in cognitive function and memory, but this varies widely among individuals and some centenarians can keep normal cognitive abilities due to the plasticity of the neural system.

Liver

The impact of aging on liver function remains a topic of limited understanding, with much of our clinical knowledge coming from transplantation surgery. While comparable outcomes have been observed in liver grafts from older donors, translating these findings to major liver resection poses challenges due to the substantial removal of liver mass.

Evidence suggests age-related alterations in liver processes, including post-transplantation deterioration of conventional liver function tests and regeneration issues, leading to poorer outcomes in older patients. Clinical studies often lack validated age cut-off values, making interpretation difficult.

Heart

As individuals age, they become increasingly susceptible to heart-related issues such as heart attacks, strokes, coronary heart disease, and heart failure. These conditions can significantly impact the quality of life for older adults and are major causes of disability. The aging process brings about changes in the heart and blood vessels. While the heart may not beat as rapidly during physical activity or stress as it did in younger years, the resting heart rate typically remains stable. However, one common age-related change is the increased stiffness of large arteries, known as arteriosclerosis or hardening of the arteries, leading to high blood pressure. 

High blood pressure, along with other risk factors like aging, heightens the risk of atherosclerosis—a condition where fatty deposits accumulate in artery walls, narrowing and hardening them. This restricts the flow of oxygen-rich blood to organs and tissues, potentially leading to heart disease. Plaque buildup in the coronary arteries can reduce blood flow to the heart muscle, causing heart damage and potentially heart failure over time. Regular blood pressure checks are essential for older individuals, even if they feel healthy, as arterial changes with age can predispose them to hypertension. Valves in the heart may become thicker and less flexible, impeding blood flow and causing fluid buildup. Additionally, heart chambers may enlarge, while the heart wall thickens, increasing the risk of atrial fibrillation—a common rhythm disorder among older individuals. 

Brain

As people age, changes occur in all parts of the body, including the brain: 

Certain areas of the brain responsible for learning and complex mental tasks may shrink. 

Communication between neurons in specific brain regions may become less efficient. 

Blood flow to the brain may diminish and inflammation, a response to injury or disease, may rise. These brain changes can affect mental function, even in healthy older individuals. 

For example, some may notice difficulties in complex memory tasks or learning, although they often perform equally well given extra time. This adjustment period is normal with aging. Evidence suggests that the brain retains the ability to adapt, enabling individuals to tackle new challenges as they age. The brain governs various cognitive functions such as memory, decision-making, and planning, crucial for daily tasks and independent living. 

Common cognitive changes with aging include: 

Older adults may take longer to find words or recall names. Challenges may arise in multitasking abilities. There may be mild decreases in attention span. However, aging can also bring positive cognitive changes. Older adults often exhibit larger vocabularies and deeper word meanings than younger counterparts, possibly due to accumulated life experiences and knowledge. Researchers are actively exploring how older adults apply this wisdom and its impact on brain function. Despite cognitive changes, older adults can still engage in various activities they’ve enjoyed throughout life. Research indicates they can:  acquire new skills, create new memories, and enhance language skills 

Lungs

Normal aging-related changes that affect the respiratory system encompass anatomical, physiological, and immunological shifts. Structural alterations include deformities in the chest wall and thoracic spine, reducing the compliance of the respiratory system and increasing the workload of breathing. The lung parenchyma experiences a loss of supportive structure, leading to the dilation of air spaces, often termed « senile emphysema. » 

With age, respiratory muscle strength declines, potentially hindering effective coughing, which is essential for clearing airways. Lung function typically matures by age 20–25, after which a progressive decline is observed. Alveolar dead space increases, affecting arterial oxygen levels without significantly impacting carbon dioxide elimination. Additionally, airway receptors undergo functional changes, becoming less responsive to drugs compared to younger individuals. Older adults may experience decreased sensation of dyspnea and a diminished ventilatory response to hypoxia and hypercapnia, rendering them more susceptible to ventilatory failure during periods of increased demand, such as in heart failure or pneumonia, potentially leading to poorer outcomes.

At least one lung is necessary for survival. While there is a documented case of a patient surviving for six days on life support after both lungs were removed until a lung transplant was performed, this is not a routine procedure and long-term survival without lungs is not possible. However, living with just one lung is feasible. Pneumonectomy, the surgical removal of an entire lung, is typically performed due to conditions like lung cancer or injury. Many individuals with one lung can achieve a normal life expectancy, although they may experience limitations with vigorous activities and may still have shortness of breath.

Kidney

Human aging is associated with molecular, structural, and functional changes in various organ systems, including the kidneys. As people age, their kidneys undergo progressive functional decline along with macroscopic and microscopic histological alterations, which are exacerbated by systemic comorbidities like hypertension and diabetes mellitus, as well as preexisting or underlying kidney diseases. Although aging itself does not cause kidney injury, the physiological changes associated with normal aging can impair the kidney’s reparative capacity, making older individuals more susceptible to acute kidney disease, chronic kidney disease, and other renal conditions

Cell senescence plays a crucial role in renal aging, involving numerous cellular signaling mechanisms. Many of these mechanisms could potentially be targeted for interventions aimed at slowing or even reversing kidney aging. The clinical characteristics of renal aging highlight recent advances in understanding the role of cell senescence in this process and explore potential interventional strategies and novel therapeutic targets. 

Life is incompatible with the complete loss of kidney function, though hemodialysis can serve as a substitute. However, unlike most other organs, our kidneys are overengineered, providing more capacity than necessary. In fact, a single kidney with just 75 percent of its functional capacity can sustain life effectively.

Thymus

The thymus is one of the useful organs, but not necessary for our survival. The size reduces with age and totally disappears for many people aged 60 or more.

Surgical removal of the thymus (thymectomy) is occasionally necessary for treating conditions like thymic tumors or myasthenia gravis. People can live without a thymus. However, studies have shown that removing the thymus in infants is linked to a higher risk of infections and autoimmune disorders. Adults who undergo this procedure typically experience fewer adverse effects.

You can also live without your pancreas, spleen, and gallbladder, as well as without organs such as your appendix, colon, and, for women, the uterus and ovaries. We can also live with only one lung or one kidney. However, living without these organs requires some lifestyle adjustments. It’s important to take any prescribed medications, monitor your blood sugar, and stay active.

Life of the organs after death

Organs have varying durations of viability after death, dictating the urgency of matching them with recipients. Here’s a breakdown: 

Heart: 4-6 hours 

Lungs: 4-6 hours Similar to heart transplants. 

Liver: 8-12 hours. 

Kidneys: 24-36 


Conclusion

Aging is a fascinating process that slowly affects all parts of your body. To find a way to escape senescence, we will need either to find a way to stop senescence in each part of the body or, more probably, to find a global way and check if it is working for all body parts.


The good news of the month: In Europe, we live longer than ever before.

In Europe, we live now longer than before the Covid-19 period. in 2023, life expectancy at birth in the EU was 81.5 years, up 0.9 years from 2022 and 0.2 years from the pre-pandemic level in 2019, data released by Eurostat on May 3.

This is a very positive evolution and the best progress in one year since many years. This means also that the negative consequences of the covid-19 are finally behind us.

In 15 out of 27 countries, life expectancy exceeded the EU average, with the highest expectancy recorded in Spain (84.0 years), Italy (83.8 years), and Malta (83.6 years). On the opposite side, the lowest life expectancy at birth is in Bulgaria (75.8 years), Latvia (75.9), and Romania (76.6).


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Heales Monthly Newsletter. The death of death N°180. April 2024. Organ-on-a-chip


The use of Artificial Generative Intelligence systems by healthcare professionals must become widespread; it would be unethical to do without the help of these tools.

Ethical principle of the French Academy of Medicine (translation). Generative AI systems in healthcare: challenges and prospects, 5 March 2024.


This month’s theme: Organ-on-a-chip


Introduction

Organ-on-a-chip (OOC) is a technology that involves the creation of microfluidic cell culture devices that simulate the activities, mechanics, and physiological responses of entire organs or organ systems. 

These chips typically contain small chambers lined with living cells that mimic the structure and function of specific organs, such as the heart, liver, lung, or kidney. The purpose of organ-on-a-chip technology is to provide a more accurate model of human physiology compared to traditional 2D cell cultures or animal testing. 

By recreating the microenvironment of an organ, including factors like fluid flow, mechanical forces, and cell-cell interactions, researchers can study disease mechanisms, test drug efficacy and toxicity, and even personalize medicine. Each chip can replicate certain functions of its corresponding organ, allowing researchers to study interactions between different organs and systems in the body, known as « body-on-a-chip » systems. This technology has the potential to accelerate drug discovery, toxicology testing, and personalized medicine by offering more reliable and relevant models for studying human biology and disease. Some aspects related to aging have been studied, but following interactions between organs on a long-term scheme and with senescence aspects is still to be done.

The difference between an organ on a chip and an organoid is that OOCs are microfluidic devices mimicking entire organs’ physiological responses, offering precise control over microenvironments for drug testing and disease modeling whereas the organoids are 3D cell clusters derived from stem cells, replicate specific organs’ structures and functions, serving as valuable tools for studying development, diseases, and personalized medicine, albeit with less control over microenvironments

Comparison of characteristics of 2D and 3D cell cultures

 

 

 

 

Types of Organ-on-a-chip

Lung

A study from 2021 shows that the lung-on-a-chip technology utilizes a biological, stretchable, and biodegradable membrane composed of collagen and elastin, simulating an array of miniature alveoli with dimensions akin to those found in vivo. This membrane undergoes biodegradation, and can be easily customized in terms of thickness, composition, and stiffness through a straightforward manufacturing process. The air-blood barrier is reconstructed using primary lung alveolar epithelial cells sourced from patients alongside primary lung endothelial cells. Notably, the membrane maintains typical alveolar epithelial cell markers and preserves barrier properties for up to three weeks.

Kidney

By utilizing kidney-on-a-chip technology, researchers can replicate physiological conditions found in human organs. Various kidney-on-a-chip models have been created to mimic the microenvironment of the kidney tubule, demonstrating improved accuracy in predicting drug nephrotoxicity compared to traditional methods. Using kidney-on-a-chip platforms, researchers can assess diverse drug-induced biological responses. In the future, the integration of kidney-on-a-chip into multi-organ systems is anticipated. Furthermore, kidney-on-a-chip holds promise for disease modeling and advancing the development of novel renal replacement therapies

Pancreas

The Pancreas-on-a-chip platform emulates the native functionality and cellular interactions of pancreatic cells more accurately than conventional human cell culture models. This chip facilitates the replication of fluid flow dynamics observed in vivo. Utilizing the Pancreas-on-a-chip has contributed to addressing a fundamental question in cystic fibrosis-related diabetes (CFRD): whether the loss of Cystic Fibrosis(CFTR) function in pancreatic duct epithelial cells (PDECs) is a primary factor in CFRD development. A study suggests that indeed, CFTR dysfunction in PDECs is a significant contributor to CFRD onset. 

Heart

Cardiovascular diseases (CVD) stand as the primary cause of mortality in numerous countries. However, the development of cardiovascular drugs faces significant hurdles: (a) Animal models for CVD often inadequately predict human responses; (b) Adverse effects vary between organisms; and (c) The process is lengthy and costly. Organs-on-a-chip technologies have been proposed to mimic the dynamic conditions of the cardiovascular system particularly, the heart and general vasculature. These systems pay particular attention to mimicking structural organization, shear stress, transmural pressure, mechanical stretching, and electrical stimulation.

A beating heart-on-a-chip has been engineered with highly functional micro-engineered cardiac tissues, enabling the prediction of hypertrophic changes in cardiac cells. This innovative device demonstrates the capacity to produce cardiac microtissues with enhanced mechanical and electrical coupling among neighboring cells. Furthermore, the model exhibits a positive chronotropic effect when exposed to isoprenaline, suggesting its potential utility in drug discovery and toxicity studies.

Companies involved in developing the technology

Several major companies are leading the development of organ-on-a-chip models across the globe. In Europe, we have Mimetas, headquartered in the Netherlands, which offers a wide range of organ-on-a-chip models including kidney, gut, tumors, and others. Elvesys, based in France, focuses on developing microfluidic systems. AlveoliX, located in Switzerland, specializes in human lung-on-a-chip models. TissUse, based in Germany, offers multi-organ-on-a-chip solutions. Lastly, BiomimX, headquartered in Italy, is renowned for its expertise in generating predictive models of human organs and pathologies for drug testing.

Emulate, one of the leading companies in the field, is based in the U.S. and specializes in creating advanced models such as lungs-on-chip, gut-on-chip, and blood-brain-barrier-on-chip systems. AxoSim, based in the U.S., is dedicated to creating specialized microfluidic chips for combating cancer. TaraBiosystems, another U.S.-based company, is known for its focus on heart-on-a-chip models. Nortis Bio, based in the U.S., specializes in kidney-on-a-chip models. BioIVT, also headquartered in the U.S., provides established models such as pancreatic islets and lung airway epithelium. 

Use of Organ on a chip in longevity studies

Organoids and microfluidic chip technology represent significant advances in molecular biology. Organoids, miniature models of organs generated from stem cells, effectively mimic the morphology and function of actual organs. On the other hand, organs-on-chips employ intricately carved tunnels on plastic or polymer surfaces to house cells, stimulating blood flow within the human body. These technologies have emerged as solutions to the challenges of drug development, which is often slow, costly, and prone to failure due to inadequate predictive tools. By combining organoids and organs-on-chips into « organoids-on-chips, » researchers can leverage the biological accuracy of organoids with the dynamic capabilities of microfluidic chips, enabling a more accurate study of disease traits and drug responses. For instance, integrating a functional vascular system into organoids enhances their complexity and physiological relevanceThe potential of organoids-on-chips extends beyond drug screening to applications in regenerative medicine and fundamental biological research. These technologies could revolutionize medical research and drug development practices, potentially replacing animal testing in toxicology studies and developing personalized therapies.

BIOFABICS, a Portuguese start-up funded by the European Union’s Horizon 2020 research and innovation program, is pioneering custom design tools for bio-fabrication, particularly in the emerging field of organ-on-chip (OOC) technology. The goal of the company is to leverage automated customization processes, allowing users to create large arrays of interconnected organ models. Currently, BIOFABICS is primarily engaged in pre-clinical research. 

In 2022, NASA, in collaboration with the National Institutes of Health (NIH), the Department of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA), and the Food and Drug Administration (FDA), selected 8 research projects to enhance the longevity of 3D tissue chips to a minimum of 6 months. This multi-agency effort aimed to achieve tissue viability and physiological function extension through automated engineering capabilities, enabling real-time online readouts in complex human in vitro models, such as tissue chips or micro-physiological systems. The scientific objectives of this initiative included gaining deeper insights into disease models, facilitating drug development, optimizing clinical trial design, understanding chemical and environmental exposures and countermeasures, and investigating physiological changes induced by the spaceflight environment. Critical to the success of these endeavors is the in-depth characterization of tissue chips, particularly in distinguishing between acute and chronic exposures, marking a significant advancement in the evolution of these technologies.


The good news of the month: Rejuvenating Aged Immunity by Depleting Myeloid-Biased Stem Cells


Researchers of the University of Stanford (USA) found that depleting myeloid-biased hematopoietic stem cells (my-HSCs) in aged mice rejuvenated their immune systems, boosting lymphocyte progenitors, naive T cells, and B cells. This led to improved immune responses to viral infections, pointing to a potential approach to combat age-related immune decline and inflammation.


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Heales Monthly Newsletter. The death of death N°179. March 2024. Questions related to the sharing of health data for longevity


Age reversal works in primates to restore vision. Next up: age reversal in humans.

-David Sinclair (see also Good News of the Month below). Source.


This month’s theme: Questions related to the sharing of health data for longevity


Introduction

We have decades of health data for billions of people. We have also data on smartphones and wearables about the activities of hundreds of millions of citizens. We could potentially see almost in real time what of are the effects of all the drugs used in many countries to cure and prevent diseases related to old age. We could see the effects of drugs combined, constant if new diseases appear or on the contrary, if patients are going better, see if people have more or less physical activities.

However, for this to be possible, we need not only data but data that we can access. At the moment, we have situations where we overuse some data and do not use most other data. The principal obstacles are questions related to privacy, private interests to keep data available only to a few, and curation. In this newsletter, we will not approach questions related to the « property » of data.

Questions related to privacy.

There are two main ways to respect privacy before sharing health data: anonymization and pseudonymization.

Anonymization is the process of removing or altering personal or identifiable information from data so that the individuals to whom the data pertains cannot be readily identified. In simpler terms, it’s a way to hide someone’s identity in a dataset. In this process, theoretically, there is no way back, once the data is anonymized, one cannot anymore know who was the person with the information.

Pseudonymization is the technique used to replace or encrypt personally identifiable information in data with artificial identifiers, or pseudonyms. These pseudonyms allow the data to be used for analysis or other purposes while still protecting the identity of the individuals involved. It’s like giving each person in a dataset a fake name or code to protect their real identity. In this process, theoretically, you can find the information back (by replacing again the pseudonyms with the real names).

Anonymization is better for privacy but less good for research. Because for research, sometimes you need to find out more about the subjects of the experiment after the experiment is started. And anonymization makes it impossible to find more.

Of course, in any situation, it is also important to remember concerning privacy for health data that:

  • It must be prohibited for researchers to use data for other goals than for research.
  • Access to data has to be registered and kept for a long period so that potential users know they risk being in trouble for an illegitimate use even if this misuse is detected after a long time.

Curation

Health data curation refers to selecting, organizing, and managing health-related data to ensure its accuracy, relevance, and accessibility for healthcare professionals and researchers. Health data curation aims to improve the quality and usefulness of health data for analysis, research, diagnosis, treatment, and public health initiatives. We need institutions like Data Curation Centres (DCC)

Here are some examples of data curation in action:

  • Data Acquisition: This phase entails the careful selection and procurement of data from a multitude of origins, spanning databases, online platforms, and other digital repositories and from a multitude of sorts: electronic health records, medical imaging, clinical trials, and wearable devices. It also involves vetting the data to ensure its reliability and suitability for the intended purpose. 
  • Data Cleansing and Transformation: This step focuses on purging and reshaping data to enhance its utility. It involves eliminating redundant entries, rectifying inaccuracies, and standardizing data formats to facilitate analysis. 
  • Data Organization: Data has to be methodically arranged into logical groupings, be it by chronological order, classification, or source attribution. Such an organization streamlines data retrieval, utilization, and analysis. 
  • Data Accessibility: Making data readily accessible to users is paramount. This can be achieved through user-friendly interfaces, web-based tools, or Application Programming Interfaces (APIs), enabling seamless data retrieval and exploration. 
  • Data Preservation: Ensuring data longevity involves regular backups, archival procedures, and stringent security measures to safeguard against unauthorized access or loss. 

Synthetic Data: A solution for privacy? 

Synthetic data is information that is artificially manufactured and not generated by real-world events. It could be a solution to avoid privacy questions and permit better health research. However:

  • Since health synthetic data is generated based on real data, some specialists consider that they still can be considered personal data.
  • Since synthetic health data is generated based on already known information and hypotheses, it can be that it is not showing what real health data will show (synthetic data will not include « surprising » data).

EHDS

The European Health Data Space (EHDS) is a specialized ecosystem designed to enhance the management of health data within the European Union. It encompasses regulations, standard practices, infrastructure, and governance to achieve several key objectives: 

  • Empowering individuals by granting them greater digital access to and control over their health data, both nationally and across the EU. 
  • Cultivating a unified solution for electronic health record systems, pertinent medical devices, and high-risk AI systems. 
  • Establishing a reliable and efficient framework for utilizing health data in research, innovation, policy-making, and regulatory activities (known as secondary data use). 

EHDS stands as a crucial component of the broader European Health Union initiative. It builds upon existing regulations such as the General Data Protection Regulation (GDPR). The goal is to strengthen the European Health Union, ensuring that member states are equipped to address health crises effectively, have access to affordable and innovative medical resources, and collaborate to enhance disease prevention, treatment, and post-care.

Examples of how the EHDS will function

Example 1: A woman living in Portugal is going on holiday to France. She gets sick in France and needs to see a local general practitioner. Thanks to the EHDS and MyHealth@EU, a doctor in France will see on his/her computer the medical history of this patient in French. The doctor can prescribe the necessary medicine based on the medical history of the patient, avoiding for instance products to which the patient is allergic.

Example 2: A health tech company is developing a new AI-based medical decision support tool that assists doctors in making diagnostic and treatment decisions following a review of the patient’s laboratory images. The AI compares the patient’s images with those of many other previous patients. Through the EHDS, the company can have efficient and secure access to a large number of medical images to train the AI algorithm and optimize its accuracy and effectiveness before seeking market approval.

Health Data Hub example

France possesses a substantial and well-structured data repository, which presents an international competitive advantage for research and innovation. However, accessing this data for projects of public interest has historically posed significant challenges. 

In response to these challenges, the Health Data Hub was established as a public entity. Its primary goal is to facilitate access for project coordinators to non-identifiable data hosted on a secure platform, in full compliance with regulations and citizens’ rights. This platform enables the cross-referencing and analysis of data to enhance the quality of care and patient support.

Conclusion

Some perspectivists say « Data is the new oil« . We could also say « Health Data is the new penicillin » (or even more than that). Contrary to oil, (curated) health data are complicated to use not because of natural obstacles, but because of a lack of goodwill and good laws to share it, Contrary to oil, the more we use (curated) health data, the more it can be useful. It could become a precious common good. 

Health Data is one of the keys to healthy longevity. We need it to measure progress, to understand health dangers (pollution, new diseases…), to accomplish clinical trials, and to make us more human.


The good news of the month: Gene therapies and rejuvenation.


Californian researchers declared that gene therapy-mediated partial reprogramming extends lifespan in aged  (wild-type) mice. And the progress announced is important (even if only about the remaining lifespan of already quite old mice). The inducible OSK system, in those 2 old years male mice extends the median remaining lifespan by 109% over wild-type controls. 

The abbreviation OSK is used for the expression of three Yamanaka factors, Oct4, Sox2, and Klf4.

Life Biosciences (Life Bio) and David Sinclair announced tests in nonhuman primates with a new gene therapy that uses a partial epigenetic reprogramming approach to restore visual function. It is affirmed that when eyes were treated with OSK after laser damage, it significantly restored pERG responses compared to controls, consistent with restoration of vision. This is very promising even if It was not tested in old (sick) primates but on healthy subjects.


For more information

Heales Monthly Newsletter. The death of death N°178. February 2024. Reproductive system and Longevity


We believe that Reverse Aging is humanity’s most incredible quest since the space race.

Dior Manifesto


This month’s theme- Reproductive systems and longevity.


Introduction

It is a well-known fact that menopause is a process that stops fertility while andropause frequently only diminishes fertility and while many female animals do not stop being fertile until they die.

It is a less-known phenomenon that the fertility of female mice decreases rapidly at the low age of 6 months which could be very useful for studying rejuvenation treatment.

Women

Menopause marks a natural phase in a woman’s life, typically occurring around the age of 50, though it can vary. During this transition: The ovaries cease production of estrogen and progesterone. Ovulation stops, meaning pregnancy is no longer possible.

Menstrual periods cease, with menopause confirmed after a year without menstruation. It’s advised to continue contraception until this milestone. As hormone levels decline, the reproductive system changes:

Vaginal tissues may become thinner, drier, less flexible, and prone to irritation, potentially leading to painful intercourse.

The risk of vaginal yeast infections may increase. External genital tissues may decrease in size and thin out, sometimes causing discomfort.

These changes are part of the natural aging process and may require adjustments and management for women experiencing them.

Men

As men get older, their bodies go through changes in the reproductive system, which can sometimes lead to feelings of depression, mood swings, and uneasiness. This is called andropause or male menopause. However, unlike for women, fertility generally doesn’t stop.

Here are some changes that happen:

  • The testes may get smaller and less firm because they make less testosterone, which can lower sex drive.
  • Sperm count can go down by about 30% by the time a man is 60.
  • The prostate gland may shrink between 50 and 60 years old but could grow larger and possibly have cancer by age 70.
  • The glands that make semen become lighter and can’t hold as much after 60.

Reproductive system and longevity for humans

Female reproductive aging is a natural process guided by biological pathways, but it has unique aspects. Multiple recent research has uncovered the complex links between reproductive aging and the aging of other body systems, raising questions about cause and effect. It’s been found that reproductive aging can affect the aging of cells, tissues, organs, and systems throughout the body. As women reach the end of their reproductive years, they often experience a higher risk of age-related illnesses. On the other hand, the phases of menarche (first menstruation) and menopause, as well as variations in the length of reproductive life, can have social consequences. Depending on the information concerning their fertility status, women may postpone having children. By identifying and using precise aging markers, we can predict when menopause will occur and accurately determine a person’s biological and reproductive age.

A decrease in sex hormones like testosterone in men (andropause) and estradiol in women (menopause) is often linked to aging. In men, lower testosterone levels can lead to a decline in muscle and bone mass, as well as physical abilities. In women, the impact of reduced estradiol on bone health is well understood, but it needs to be clarified whether it affects muscle mass and physical function. However, lacking multiple important hormones can indicate poor health and a shorter lifespan in older adults. It’s worth exploring if hormone replacement therapies could help manage conditions like age-related muscle loss, cancer-related weight loss, or illnesses. If used carefully in the right patients, hormone replacement therapies prevent or reverse muscle and bone loss, maintain physical function, and support healthy aging and longer life.

Female sex cells, similar to some other cells in the body, have limitations—they can’t divide or live for extended periods, leading to the accumulation of DNA damage associated with aging. However, their crucial function is to pass on genetic information to the next generation. Importantly, these aging sex cells don’t contribute to the creation of offspring, ensuring that children don’t inherit age-related changes. This highlights a distinct way in which sex cells seem to sidestep aging, setting them apart from other body cells.

The reasons behind early and premature menopause, a type of rapid reproductive aging, are diverse. Chronic conditions that lead to ongoing inflammation in the body can play a role, either directly or indirectly. Genetic predisposition, autoimmune disorders, and infectious diseases are commonly associated with premature ovarian insufficiency, a condition linked to early menopause.

Lifespan differences for female and male mice

The Interventions Testing Program (ITP) assesses potential compounds for their ability to delay aging, measured through increased lifespan and/or postponed onset or reduced severity of age-related diseases for mice. We can see a difference in results when both sexes are compared.  A study shows that in female mice, the combined administration of both Rapamycin and acarbose did not result in a lifespan that was either longer or shorter than what was previously observed with only Rapa treatment. This outcome might be due to the modest survival advantages observed in earlier groups of female mice receiving Aca alone. Another study showed that Canagliflozin extends life span in genetically heterogeneous male but not female mice and 17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Rapamycin seems to be the only drug that consistently shows an increase in median and maximal lifespan in female mice. A study showed that Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice.

Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors), and delayed spontaneous cancer. 22.9% of rapamycin-treated mice survived the age of death of the last mouse in the control group. Thus we demonstrated for the first time in normal inbred mice that lifespan can be extended by rapamycin. This opens an avenue to develop optimal doses and schedules of rapamycin as an anti-aging modality.

There isn’t much information available on why we see this difference in the effect of various anti-aging compounds between males and females but speculation is that female sex hormone and uterus functioning have an effect on the rate of aging in these female mice

Conclusion

It could be imagined that the organs around the cells that will be generating the next generation do age slower than the rest of the body or even do not age. This is not the case. Even the cells that will generate a new human will « rejuvenate » after the foundation and the first divisions of cells. One day, we hope, we will be able to learn how to replicate a similar process for all cells.


The good and strange news of the month: Fish Centenarians found in the Desert (buffalofish)


A recent interesting video explains that in 1919, humans that are today all dead, decided to populate an artificial lake with three species of edible fish called buffalofishes.

The fish came from the area of the Mississippi River. The new environment was lakes in a desertic area of Arizona. Today, 90% of buffalofishes captured from the Apache Lake are more than 80 years old, and some of the original buffalofishes from the Arizona stocking in 1918 are likely still alive and in good shape. And there is more: the new environment of those fishes is good enough to enable a very long life (more than twice as long as what was known as the maximal lifespan of those fishes before), but seems not good enough to allow reproduction, at least for many years. Is there a link? An elixir of long life dissolved in the water, but making reproduction impossible. We have to hope for more information.


For more information

Heales Monthly Newsletter. The death of death N°177. January 2024. Different lifespans of animals: Very long, very short, in the real world and the labs

Imagine a rather educated mouse wondering whether it’s theoretically possible to live longer than the average life expectancy of two and a half years? Of course, it’s possible, » she’d say, « just look at the human species (…), mammals like us who live thirty to forty times longer! (translation) Au-delà de nos limites biologiques: Les secrets de la longévité. 2011. Miroslav Radman.


This month’s theme. Different lifespans of animals: Very long, very short, in the real world and the labs


Most people consider a lifespan of 80 years as something logical and good. If our normal lifespan was 20 years or 300 years, we would probably regard it as logical and good as well. Philosophers and religions would explain convincingly why shorter or longer lives would be bad. 

A normal lifespan for animals with senescence can vary in extreme ways, from a few days to a few centuries. There are even some specific animals that never age and can live for thousands of years and others who die before they are born. Concerning our close cousins mammals, the variation goes from two to two hundredth years. In this newsletter, we will approach animals with the longest life, and with the shortest lives and animals we study in the laboratories to understand their longevity.

Biologically immortality

Biological immortality means no irreversible senescence. This implies, among other things, that fertility is not decreasing with age. It has been said of quite a few animals. However, systematic observation for centuries is impossible and in most cases of affirmation of biological immortality, no lifespan of centuries is proved.

It can be noted, concerning life outside of the animal reign, that some plants, especially some trees, but also posidonia, and unicellular living beings seem biologically immortal.

Turritopsis nutricula

Turritopsis nutricula, commonly known as the « immortal jellyfish, » has captivated the scientific community due to its extraordinary ability to reverse its aging process and potentially achieve biological immortality. This unique jellyfish species, found in oceans worldwide, starts its life as a polyp, an underwater life form attached to the seabed. As it grows, Turritopsis nutricula gradually transforms into a jellyfish. In times of difficulty, it can regress to the polyp stage before transforming back into a jellyfish, capable of repeating this cycle indefinitely. This organism can reverse its mature cells back into their earliest form, essentially restarting its life cycle. Of course, the concept of biological immortality is complex but the remarkable rejuvenation ability of Turritopsis nutricula offers fascinating insights into the possibilities of life extension in the animal kingdom.

They are other animals (and plants) who do not show senescence. However, most of those animals (and of course plants) do not have a brain. Glass sponges, some corals, and maybe tubeworms can reach thousands of years. Hydra’s, planaria also do not seem to age, at least for the individual reproducing asexually. Lobsters also do not age. But they also do not stop growing and they will die at one moment because they become too big to survive. Tardigrades seem not to age when in cryptobiosis. Rougheye rockfishs and naked mole rats (see below) are also sometimes mentioned as biologically immortal but with no animal older than 100 known.

Very long life

The main characteristics of animals living very long are big size, low metabolism, and few predators. But not all those characteristics are necessary for very long-living animals. In general, vertebrates flying or living underground (for example olms in caves) tend to live longer.

Greenland shark

The Greenland shark, scientifically known as Somniosus microcephalus, is renowned as the longest-living vertebrate globally, with estimated lifespans of up to 512 years. Inhabiting the Arctic and North Atlantic waters, they don’t reach sexual maturity until they’re over a century old. These sharks owe their exceptional longevity to factors such as a slow metabolism and their cold-water habitat. This extended lifespan presents a unique opportunity for scientists to delve into the biological mechanisms behind their remarkable longevity, offering valuable insights into aging and adaptation in extreme environments.

Whales

The only mammals living longer than humans are whales. It is somehow logical for one of the biggest animals in the world, with no predator when adult. They probably can live more than 2 centuries.

Tortoises and sphenodons 

The extreme longevity of some tortoises, especially coming from the Galapagos is well-known and logical for animals of a big size, with no predators before humans came and a low metabolism. The oldest living turtle is 192 years old.

Less well-known are the Tuatara’s (sphenodons) who can live and lay eggs after more than one century.

Grey parrots

Parrots, known for their exceptional cognitive abilities and unusually lengthy lifespans, until 83 years, may correlate with these traits, according to a study led by Max Planck researchers. The study examined 217 parrot species, including well-known ones like the scarlet macaw and sulfur-crested cockatoo, which exhibit remarkably long lifespans of up to 30 years, typically observed in larger bird species. The researchers proposed a potential explanation for this longevity: a significant correlation between large relative brain size and extended lifespan. 

Albatrosses

A Laysan albatross named Wisdom is the oldest known wild bird (more than 70 years).  It is also the bird to have laid an egg at the oldest age: 68.

Bats

In contrast to various aging theories, bats, despite their elevated metabolic rate, exhibit remarkable longevity, living approximately three times longer than other mammals of comparable size. The mystery surrounding how bats achieve this extended lifespan has garnered significant attention, often drawing parallels to immortal fantasy figures like Dracula from Bram Stoker’s novel. Numerous ecological and physiological characteristics, including diminished mortality risks, delayed sexual maturation, and the ability to hibernate, have been associated with the prolonged lifespan observed in bats. Despite these insights, there remains a scarcity of information regarding the specific molecular mechanisms that contribute to the exceptional longevity observed in bats.

Eusocial insects and larvae.

Queens (this means reproductive females) and sometimes kings (reproductive males) of eusocial insects like bees, ants, and termites can live a much longer life than most insects. The record is 8 years for bees, for ants almost 30 years, and for termites, it is roughly 30 to 50 years. What is particularly interesting for those animals is that so-called workers or soldiers have often the same genes, but live lives tenths of times shorter. It would be interesting to know if some mechanisms allowing a much longer life for some insects can somehow be duplicated by mammals.

Some insects have a very long life as a larva. The longest normal larva period concerns periodical cicadas living 17 years as a larva (and then massively becoming adults to limit predation). Splendour beetles can be larvae during an even longer period. The longest recorded period is 51 years.

Very short lives

We wrote that animals with a very long life have usually a big size, a low metabolism, and few predators. Unsurprisingly, animals with a very short life are usually small, with a fast metabolism, and with many predators.

Some of those animals (C Elegans, drosophila, Nothobranchius, mice, and rats are studied in the laboratory and will be approached in the third part of this newsletter.

Many insects are considered to have a very short life but have a longer life during their larva phases. The famous mayflies who live only days, even hours or minutes as an adult and many species of butterflies who do not eat when they are adults have a nymphal of several months to several years,

The strange (non-)life of some mites.

The strangest shortest known lifespan is the life of males Acarophenax tribolii. Their lifespan is less than nothing because they die before they are born!   The mother Acarophenax produces young in a ratio of 15 females to one male. The male copulates with all its sisters during gestation and dies when still in the womb of the mother. The mother later literally explodes and dies, releasing her young daughters already pregnant. And the cycle starts again, they will grow and give birth by exploding.

Gastrotrich 

It is a very small worm-like animal found in freshwater areas everywhere in the world. The whole lifecycle can happen in 2 days, but it can also be longer than 40 days.

Chameleons

The terrestrial vertebrate with the shortest life is the Labord’s chameleon. He normally lives less than 6 months. It is an interesting animal because other chameleons, genetically probably not very different, can live up to 10 years. However, it must be said that apparently in favorable situations, some animals live longer.

Mammals. The shrew and the male antechinus.

The mammal having the shortest life for males and females is the common shrew. This very small carnivore animal will normally not live longer than one year. It is less than rats and mice that are abundantly suited for longevity, but far less easy to breed.

The male antechinus is a small marsupial that lives less than one year, dying during or just after the period of reproduction. This is sometimes called « suicidal reproduction ».

Roundworms 

 and their mammalian counterparts suggests that the roundworm will continue to be a valuable animal model for the study of aging. 

Fruit flies 

The Turquoise killifish is an extremely interesting freshwater fish for the study of aging. It is easy and not expensive to breed. It is so easy and nice that people keep it as a pet. It has also the shortest life of all vertebrates but one (Eviota sigillata, a sort of Gobi). The Kill fish has remarkable capacities for regeneration but will live for a maximum of twelve weeks. Hundreds of scientists around the world are studying the animal to try to understand and solve the fascinating questions of senescence. They do not study as much Eviota sigillata who live an even shorter life of a maximum of 59 days, because breeding this small saltwater fish is far more complicated. Another fish that must used for scientific studies is the Zebrafish, because of its capacity for regeneration. This animal can live up to 5 years in an aquarium

Animals in the laboratories

From widely used model organisms like fruit flies (Drosophila melanogaster) and nematode worms (Caenorhabditis elegans) to more complex mammals such as mice and rats, researchers explore various species to understand the genetic, physiological, and environmental factors influencing lifespan. Additionally, unconventional subjects like bats and parrots have recently captured scientific interest due to their exceptional longevity despite high metabolic rates. These animals serve as valuable models to investigate the intricate mechanisms that contribute to prolonged lifespans, shedding light on potential insights applicable to the broader spectrum of life, including humans.

Roundworms 

Caenorhabditis elegans is a roundworm with a 20-day lifespan, making it a good subject for research. More than 400 genes that extend lifespan in roundworms have been described. Among the genetic controls studied are a series of interacting proteins that act like insulin and control reproduction and longevity. Investigators have also looked at a mechanism controlled by a group of genes called clock genes. These regulate metabolism in the roundworm and affect lifespan. The roundworm genes that seem. to confer increased longevity do so by supporting resistance to external stresses, such as bacterial infections, high temperatures, radiation, and oxidative damage. The correlation between the existence of roundworm genes and their mammalian counterparts suggests that the roundworm will continue to be a valuable animal model for the study of aging. 

Fruit flies 

Drosophila melanogaster, or the fruit fly, is a favorite subject for studies on longevity. Researchers have identified one gene that they have named Methuselah, which can increase fruit fly life span by 35 percent. Molecular physiologist Xin-Yun Huang of Cornell University’s Weill Medical College in New York City has been conducting research to uncover what activates the Methuselah protein. Huang and his team found that another protein, the Sun protein, binds to Methuselah and alters fly longevity. Flies with a disabled copy of the Sun gene lived 50 percent longer than control flies. A number of studies on a fruit fly gene called Indy (for “I’m Not Dead Yet”) have been published. Because the fruit fly has genes such as Indy that produce proteins very much like human proteins, it makes an excellent animal model for aging research.

Nothobranchius furzeri

The Turquoise killifish is an extremely interesting freshwater fish for the study of aging. It is easy and not expensive to breed. It is so easy and nice that people keep it as a pet. It has also the shortest life of all vertebrates but one (Eviota sigillata, a sort of Gobi). The Kill fish has remarkable capacities for regeneration but will live for a maximum of twelve weeks. Hundreds of scientists around the world are studying the animal to try to understand and solve the fascinating questions of senescence. They do not study as much Eviota sigillata who live an even shorter life of a maximum of 59 days, because breeding this small saltwater fish is far more complicated. Another fish that must used for scientific studies is the Zebrafish, because of its capacity for regeneration. This animal can live up to 5 years in an aquarium

Muridae

Mice and rats are the favorite subjects of scientists interested in human aging. Because they are mammals, they are more closely related to us than yeast, flies, or worms, and their relatively small size and short life span make them easier to study than long-lived animals. Much of the excitement in recent aging research has come from discoveries that aging can be postponed in mice or rats by very low-calorie diets and by discoveries of mutant genes that can extend life span by as much as 50 percent. Through targeted genetic manipulation, researchers have already created genetic lines of mice that model Werner’s syndrome (premature aging), Alzheimer’s disease, other neurodegenerative conditions, atherosclerosis, diabetes, immune dysfunction, musculoskeletal disorders, oxidative stress, and many other medical conditions associated with aging. Other studies are using mice engineered to make them particularly vulnerable to DNA damage or damage to their mitochondria (energy-producing “organs” inside cells). The growing interest in mouse aging and genetics has been strongly stimulated by the sequencing of the mouse and human genomes and by the realization that most human genetic diseases can be modeled by changes in equivalent genes in these rodents.

Naked Mole Rats 

Those rodents already studied in a recent newsletter are living exceptionally long lives for a small mammal. They live in underground colonies and are relatively easy to observe in captivity. Contrary to all other well-studied vertebrates, they seem to show no senescence in the sense that their probability of dying does not seem to progress with age. However, they show other signs of aging. 

Dogs

The distant children of wolves have lived with us for so long that they acquired good and bad habits. They are so culturally and physically close to us that they are ideal to compare with us. And since we have millions of them of old age, it will be extremely easy to start experiments on longevity with animals of old age. It could even be in combination with treatments with their well-informed owners.

Nonhuman Primates

The discovery that fruit flies and roundworms carry genes that affect their longevity is exciting, particularly because many of those genes have human counterparts. However, the fact remains that the complexity of human physiology can’t be replicated in simpler organisms such as fruit flies and roundworms. But our DNA is very similar to that of nonhuman primates such as monkeys and apes. And it is nearly identical to that of chimpanzees. The National Institute on Aging (NIA) is sponsoring an extensive series of experiments into aging and longevity using primate models, including rhesus and squirrel monkeys. Rhesus monkeys are particularly useful because the rate of aging in rhesus monkeys is three times as fast as the rate in humans. It is important to say, in ethical terms, that the goal and result of the experiments is to allow a longer and healthier life for primates and consequently for humans. Primate studies are ongoing in neurobiology, skeletal deterioration, reproductive aging, and other age-related diseases such as heart disease and diabetes. Results from studies of caloric restriction and its impact on aging in primates are also available.

The good news of the month: LEVF experiments are progressing

The Longevity Escape Velocity Foundation is pursuing an experiment on 1,000 mice. After about 10 months, the results are already very promising, especially concerning the female mice with a big difference in mortality between mice with no treatment and mice with all treatments.

A second study is in the preparation mode, subject to. The interventions would be:  Deuterated Fatty (Arachidonic) Acids, Mouse Serum Albumin, Mesenchymal Stem Cells, and Partial Cellular Reprogramming

It is to be hoped that the LEVF will soon not be anymore the only working longevist organization working on a large number of old mice observed until their death with a promising treatment. Organizations like Hevolution, Google Calico, the Chan Zuckerberg Foundation, and Altos Labs should use a few million dollars among their billions to test their most promising ideas on our mammalian short-living far cousins.


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