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Clinical Trials For Healthy Longevity That Are In Progress Or Could Be Started Immediately

One of the main challenges of research for healthy human longevity is to organize reliable studies (double-blind…) and to publish the results (even if they are not positive).

This page gives a list of what the organization Heales considers the most important and promising clinical trials that have already been started or should be started as soon as possible. As the studies are in progress, it is important to keep ourselves updated on the latest news which included criticism from the scientific community.

This list is intended to be a starting point. You are more than welcome to comment or make other suggestions.

An article about trials on animals will be published later.

  1. TRIM study Thymus

The thymus is a primary lymphoid organ essential for the development of T cells. These T cells are majorly responsible for adaptive immunity or the first line of defense against bacteria, viruses, and also tumors in the body. As time passes, the thymus goes under programmed cell atrophy known as involution. All T cells are produced at a young age as the thymus is at its largest size in children. As people grow older, the thymus starts to shrink and involution especially hits the immune system of people between the ages of 65 and 75. Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial (TRIIM-X) by scientists at Intervene Immune were originally run from 2015 to 2017 on participants from age 50-65 that are healthy men that received a combination of growth hormone DHEA and metformin with an objective of reversing thymic involution. The results were promising they show that the participants showed an increase of more than two years in the predicted human lifespan. This was seen throughout the various epigenetic clocks including the GrimAge clock that analyzes DNA methylation. As of today, they have started another trial with similar objectives and are currently looking for volunteers. FDA has not approved this therapy yet but TRIIM-X Trial was the first of its kind to show regression in multiple age-related biomarkers possible in humans.

2.  Metformin TAME Study 

First introduced in 1922, Metformin is a well-known drug given to patients with type 2 diabetes and is known to act by helping the body to reabsorb less sugar and hence balance the blood sugar levels. It both lowers glucose absorption after a meal, as well as increases the body’s sensitivity to insulin. It is a popular medicine as it is cheap in cost and has minimal side effects. Metformin has already shown signs of delaying aging The main aim of the TAME (Targeting age with Metformin) Trial is to study how metformin delays age-related diseases like CVD, neurological conditions, cancer, etc. Led by Dr. Nir Barzilai, the trial is set to be six years long with more than 3000 participants from the age 65 to 79. Their goal is that if the FDA declares ‘aging’ itself as a disease, then instead of targeting the different age-related conditions, they will target aging itself which will include all the conditions together.Along with the TAME trial, they also want to look for biomarkers of aging in TAME BIO by:

  • Store samples of the blood, urine, DNA, etc from all the participants to study further.
  • Use different approaches to study biomarkers that predict changes in function, multi-morbidity, and subsequent death.
  • Study the influence of Metformin on multiple age-related biomarkers on all participants using and create a report with the core data collected.

They are currently collecting funds to proceed with the trial as the TAME Trail team deeply believes that drug intervention for aging and related diseases will not only extend years of health but will also save trillions of dollars. 

3. Rapamycin

Also known as Sirolimus, Rapamycin is a macrolide compound used for preventing rejection after organ transplant, coating stents, and even as a treatment for lung and other types of cancer. It functions by targeting the mTOR which regulates the growth of our cells by binding to a subset in the catalytic cycle, blocking the function of the mTOR.

Rapamycin is currently the wonder drug with the most promising anti-aging effects.  The latest studies at the Max Planck Institute for Biology of Aging show that in young adult fruit flies, a 2-week administration of rapamycin can protect them against age-related conditions in the intestine and extend life. Then they administered rapamycin for 3 months in mice and saw similar results with beneficial intestine-related results by the time the mice were middle-aged. This short exposure to the drug is seen to be equally beneficial as lifelong administration with lesser to no side effects. Further studies will now try to answer if the geroprotective effect of rapamycin continues in humans if they start taking it later in life and what kind of dosing will be ideal.

4. Senolytics

Senolytics come under a class of drugs that clears out senescence cells (SC). Senescence is a phenomenon where the cells get arrested in the cell cycle if they sense danger stimuli. Accumulation of the SC increases with aging and can cause damage to the tissue and can be a cause of multiple diseases including various neurodegenerative diseases. 

Dasatinib (a tyrosine kinase inhibitor), Quercetin (a naturally occurring flavonoid), Fisetin, and Navitoclax were the first senolytic-drugs introduced in the market following a hypothesis-driven approach. A combination of Dasatinib and Quercetin was given to mice for over two years and the results showed fewer senescence-related biomarkers as well as a lower occurrence of disc degeneration. However, this result was seen in young and middle-aged mice, not the older ones. The challenge currently lies in the lack of biomarkers specific to senescent cells. Currently, SA-β-Gal is the only available biomarker. Poor drug specificity delivery system is another challenge that the researcher needs to work out. More than 20 different clinical trials are being held to improve the efficiency of senolytics and the results from these will form a promising future.

5. NAD+ Charles Brenner

Nicotinamide adenine dinucleotide (NAD) is a coenzyme for redox reactions and is responsible for transferring electrons during metabolic processes. According to the study of Dr. Chareles Brenner, Nicotinamide riboside (NR) goes into the cells and nucleoside kinase puts a phosphate on by which NR is turned into NMN (Nicotinamide mononucleotide). NMN then converts to NAD and finally to NADP

6. Plasma dilution 

It is a method where the blood from an individual is extracted and then a plasma fraction of that blood is replaced by saline and albumin and this new mix is reintroduced in the body. Plasma dilution, also known as neutral blood exchange, is said to have properties that can restart the body’s regenerative capacities. 

The latest clinical trial from the University of California shows that Therapeutic plasma exchange (TPE) has the potential to restore the younger system and reduce biological aging. This study had a very small group of participants (Only 8) but has promising results with the de-regulation of 10 novel biomarkers, a youthful shift to various age-related conditions showing apoptotic regulators, and a youthful profile of myeloid/lymphoid markers in circulating cells, which have reduced cellular senescence and lower DNA damage. Further studies with the biggest participant group will confirm these results to be favorable in reducing aging.

7. Telomere

According to the Hayflick limit, we know that human cells will replicate for only a limited time and this was confirmed when scientists discovered that telomers shortens after each replication. Telomere has the function of protecting the ends of the genome from degradation and maintaining its integrity of it. Telomerase is the enzyme that catalyzes the extension of the telomeric region and the shortening of this telomeric region is associated with signaling between somatic cells for senescence. 

Shortening of telomere with age is related to factors like apoptosis, and oncogenic transformation and even affects the life and health span. The TACTIC (Telomerase ACTivator to reverse Immunosenescence in Acute Coronary Syndrome) trial from the UK had the objective to check if TA-65MD, a telomerase activator can decrease reduce the shortening of telomerase and oxidative stress.90 Patients took 1 x capsule twice daily for 1 year which may be either the test drug TA65MD (8mg) or the place. Another Clinical Trial from France Telomeres and Arterial Aging (TELARTA). Their objective is to create a model that makes it possible to examine different elements of telomere length dynamics in different tissues: leukocytes, skeletal muscle, endothelial progenitor cells (EPCs), and skin or subcutaneous fat in patients with or without atherosclerosis. The results from these and many such trials will give us a better view of future treatments. 

8. Follistatin 

Activin binding protein, follistatin, is encoded by the FST gene in humans and it is an autocrine glycoprotein, seen in most tissues. It is an antagonist of myostatin involved in increasing strength and muscle mass. This is one of the reasons why follistatin supplements are popular amongst bodybuilders.  

Follistatin gene therapy is emerging and Bioviva CEO (in 2015) became the patient zero for the therapy of both telomerase (hTERT) and follistatin (FST). A study using Mouse mouse cytomegalovirus (MCMV) carrying exogenous FST has shown an increase of 32.5% in median lifespan. Another study targeting Sarcopenia (loss of muscle mass and strength over age) showed overexpression of follistatin delivered by Adeno-associated virus (AAV) in mice aged 24-27 months caused an increase in muscle weight as well as improvement in age-related degeneration at the neuromuscular junction in mice.

9. Alpha-Ketoglutarate (AKG)

AKG is a ketone derivative of glutaric acid which is known to be used by the growing cells and is involved in the healing of wounds and injury (especially muscle tissues). As AKG is an endogenous intermediary metabolite in the Krebs cycle whose levels naturally decline during aging, many supplements are currently available for the public. Rejuvant, is a  potential life-extending compound formulation with alpha-ketoglutarate and vitamins, which has been shown to have an average of 8-year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. 

10. Khloto

Klotho is a transmembrane protein that is involved in the regulation of oxidative stress, signaling growth factors, organ protection, and control over the sensitivity of organisms to insulin and shows involvement in the aging process. 

Current studies show that higher Klotho levels in an 85-year-old will have the same size of brain and the thinking ability to that as someone who is 10 years younger. Another study shows that a 20%-30% increase in the lifespan of animals was observed after the overexpression of Klotho. With a single injection, Klotho showed improved cognition by 2 years in terms of spatial and working memory. Klotho Therapeutics is one of the leading biotech firms which strongly believes in Klotho having anti-aging properties and developing a patent-pending Klotho protein that has great potential to redefine society’s experience with aging.

Heales Monthly Newsletter.The Death of Death. N°164. November 2022. Frequently Asked Questions about Healthy Longevity

Medical, scientific, and technological progress is stronger than ever. However, this has not been enough to improve Healthy Life Expectancy. In 2020 and 2021, we had the first decrease in life expectancy at the world level in the last 75 years. To overcome this loss in life expectancy, we need better scientific cooperation, increased research, and more government-level commitment to progress. Second Brussels Declaration for Radical Healthspan Extension:  After Covid times, rejuvenation times. 6th Eurosymposium on Healthy Ageing.  November 2022.  


Theme of the month: Frequently Asked Questions about Healthy Longevity


Since 2016, the Organisation « Partei für Gesundheitsforschung » presents candidates for the German elections. On their website, they present a long text with dozens of frequently asked questions on how to defeat aging. Below, you will read a selection of five of those questions (with slight adaptations).

Q. What is meant by « longevity escape velocity »?

The « first generation » therapies for humans will not be perfect. So they will repair some ageing damage very well, some less than that while others might not work at all. If we simply keep applying the same therapies – no matter how often or thoroughly – the less well or unrepaired damage will continue to accumulate. Ultimately, we will only experience age-related decline and death at an older age.

So, to keep ageing at bay permanently, it is not enough to repeat the therapies at regular intervals. We have to improve them and apply the improved version the next time. This is where the concept of « longevity escape velocity » (LEV for short) comes into play. The term refers to the rate at which we need to improve the thoroughness of repair over time in order to prevent the overall level of damage in the body from increasing further – in other words, to keep our biological age, defined as the amount of damage in our body, constant or to reduce it. If we achieve this rate, we would therefore increase the remaining life expectancy of people receiving the treatment faster than time passes during it (for example, by more than one year per year). A 52-year-old who has a life expectancy of 80 years (i.e. 28 years remaining) would therefore add more than one year of life during his or her 53rd year. His or her life expectancy would increase to more than 81 years, and the next year to more than 82. The expected (age-related) end of their life would thus move away from people faster than they approach it.

It is to be expected that once we reach LEV, (global catastrophes and similar scenarios excepted) we will never fall below this rate again because as therapies become more thorough, the amount of damage that needs to be repaired continues to decrease (after all, the complexity of ageing is finite, not infinite). As a result, the remaining damage takes more and more time to reach a critical level and the speed needed to improve therapies also decreases.

Comparison with jumping off a cliff: the remaining life expectancy of a human being is currently constantly decreasing due to ageing, just as the distance to the ground decreases in a fall due to gravity. If you jump with a jet engine on your back, the situation is comparable to regular « rejuvenation » spurts: At first, it is inactive – so you fall. If you activate the jet engine in time (i.e. if you are not too old when the first therapies are available – we won’t be able to save them with the first therapies because they will already have accumulated too much damage), it will give you lift, slow down the fall and eventually let you climb further and further.

Q. I won’t live to see that anyway, will I?

Encouraging progress is being made and therefore it is not unlikely that a large proportion of the population alive today will benefit from rejuvenation therapies – this is true even for those already at a relatively advanced age.

The objection that people have been trying in vain for millennia to find a fountain of youth or immortality is correct. But the same is true of flight, access to space, the ability to restore paralyzed limbs and freedom from smallpox, polio, and tuberculosis: All these things have been impossible for hundreds of thousands of years until the technology needed was available and used. Now they are already available for most of the human population and are being extended to the rest.

Suppose we do nothing today to accelerate rejuvenation research. In that case, we run the risk of spending our last days wondering if we could have saved ourselves and millions of other people years of unnecessary suffering if only we had decided to act sooner.

Even if these treatments may come too late for some of us, it is still our moral duty to enable our descendants to live without age-related diseases and suffering, and that can only be done if we get to work today.

Q. How close are we?

According to US inventor and futurist Ray Kurzweil, we will reach LEV (longevity escape velocity) in ten to twelve years (as of 2018).

Bioinformatician and theoretical biogerontologist Aubrey de Grey says that we have a 50% chance of reaching LEV around the year 2036. This would mean that people who are healthy enough at that time and subsequently regularly take advantage of the latest rejuvenation therapies will never die from age-related causes.

This is based, among other things, on de Grey’s estimate that we will realize RMR (robust mouse rejuvenation) with a 50% probability in three to five years. According to de Grey, this estimate is based on an assessment of the following factors:

  • how fast the individual sub-areas are progressing
  • how much research funding will be available in the future
  • how often we find out something surprising about ageing
  • how often we develop new technologies that make the work we need to do easier
  • how difficult it will be to combine therapies when they work individually
  • how much we need to rejuvenate people to give scientists time to rejuvenate them better and stay one step ahead of damage

Regardless of these estimates, rejuvenation is a rapidly growing field of research that, as you can read under the next question, has already seen some breakthroughs. The first components of a comprehensive anti-ageing therapy, such as senolytics, are already being tested in clinical trials. Others are on the verge. This should give us confidence that we are in for a revolution in biomedical research – and subsequently in human life – in the next few decades.

Q. Are there already successes?

Yes. The SENS Research Foundation, the leading research institution in the field of the SENS approach to rejuvenation, has a list on its homepage of all publications in scientific journals that originate either from its in-house laboratory or from research projects funded by the foundation.

This Wikipedia article is very helpful in tracing the history of the research field so far.

Here is a roadmap showing which stages of development the individual components of the targeted therapies are in. Not only the scientific but also the organizational, public, and political progress.

Q. What can I do today to age more slowly?

Although there is evidence that some molecules can delay or even reverse individual ageing processes, there is no currently available intervention that has been shown to slow ageing in humans. Leading candidates among currently available interventions include caloric restriction, rapamycin, SGLT-2 inhibitors (especially in men) and 17-alpha-oestradiol (again in men). Even if they work, however, their potential is much lower than that of the direct harm-reversal therapies of the SENS approach, and they cannot be replicated in a similar way.

Q. How can I accelerate progress in this area?

If you want to contribute to the faster development of more effective rejuvenation medicine, you can start in small ways: Creating broader public awareness of rejuvenation therapies by talking about them with friends, school or work colleagues or family members, donating books on the subject to libraries, doctors’ offices or hospitals, and donating money to organizations dedicated to fighting ageing (some of which can be done for free, for example through AmazonSmile).

Of course, if you are a billionaire, a scientist, or a student in fields potentially useful for rejuvenation, or if you have more time for activism, today may be the first day of the rest of your life as a professional longetivist. You could one day save many lives, including your own, your parents or your children’s.


The good news of the month: 1,000 mice will live as long as possible in good health and a promise of total commitment to longevity


Longevity trials on mice were announced by Aubrey de Grey and the Longevity Escape Velocity Foundation. They should begin as soon as January 2023 with 1,000 mice 18-month-old who will follow 4 different therapies. We should have results before the end of this year.

Alex Zhavoronkov expressed a beautiful Longevity Pledge : (…) In my opinion, there is no cause more urgent, more altruistic, more impactful, more important, and more ambitious than enabling humans to improve continuously. (…) Therefore, I would like to pledge everything I have now, and what I will get in the future, to only one cause — extending healthy productive longevity for all human beings. Instead of donating just a portion of my wealth and energy to this cause, I would like to do more. I pledge to spend 100% of my time and personal resources to accelerate research and clinical deployment of longevity technologies. (…)


For more information

HEALES MONTHLY LETTER. THE DEATH OF DEATH NO. 163. October 2022. Aging in the International Classification of Diseases (ICD)

I grew up in New Zealand and lived there until I was 12 years old. I remember one time my grandma came to visit us and I had never hung out with somebody older than the age of 60 before. When she came, I remember for the first time realizing that when I go and play with my brother, I could run around and roughhouse, but for my grandma, just getting up from a chair is really painful for her and that struck me as oh she has a disease like we should try to find a way to cure her so she can come and play with us” and then I remember asking my parents “what disease does grandma have” and they said, “she doesn’t have it, she’s just old” and I said “what disease is that”, They said “you do not understand it is a natural process” and as a kid, I thought that was stupid you know, why is it a natural process that we should all get this disease: Laura Deming, biological researcher, HT Summit 2017.


Theme of the month: Aging in the International Classification of Diseases (ICD)


What is a disease and what is the International classification of diseases?

A negative effect on the functioning of the body of an organism and its structure over a prolonged period of time is termed as a disease. Diseases come with a set of signs and symptoms and can either be caused externally (due to a pathogen) or internally (Immune system dysfunction). What is considered a disease changes with medical knowledge, but also with social and cultural evolutions. Historically, some poor areas considered obesity to be a sign of wealth, but in today’s world, we consider it to be a complex disease. In a similar context, homosexuality was also considered a “mental illness” but in 1973, the Diagnostic and Statistical Manual of Mental Disorders (DSM) removed “Ego-syntonic Homosexuality »

In 1893, the Bertillon Classification of Causes of Death was introduced to the congress of the International Statistical Institute in Chicago by the French physician Jacques Bertillon and then adopted by several other countries. This system was based on the principle of “distinguishing between general diseases and those localized to a particular organ or anatomical site”. The first edition was published in 1900 and until the sixth version, very few changes were made. In the 6th edition, which came out in 1949, the title was modified to reflect the changes: International Statistical Classification of Diseases, Injuries, and Causes of Death (ICD). From this point onwards, World Health Organization (WHO) started preparing and publishing the revised versions of the ICD every 10 to 15 years. 

Is aging a disease for the ICD?

The question to know if aging is a disease or not is a controversial one.

Aging is slowly killing all humans of the world (who are not dying of other causes). To know if it is a disease or not is a semantic question. What is sure is that is it the common cause of all age-related diseases and an aggravation factor of almost all illnesses.

ICD-10 (in 1990) already included code R54 for Age-related physical debility, R41.81 for Age-related cognitive decline, and F03 for Senile psychosis.

In the latest ICD-11, codes were introduced for a better understanding of the diseases and within that, XT9T code referred to  “age-related” and MG2A, defined as “Old Age” which was later replaced by “Ageing-related decline of intrinsic capacity” after receiving criticism.

In fact, a group of scientists from Latin America opposed the idea of including the broad term of “Old Age” as a disease fearing reinforcement of the widely prevalent ageistic beliefs in society. They argue that aging might lead to some chronic medical or mental health conditions but that other factors play a much greater role in the disease causation rather than age itself. According to them, Frailty is a much more homogeneous and better-defined clinical entity.

Ageism can indeed be a problem in many societies. Still, the immense majority of sufferings due to aging come from diseases and infirmities due to senescence that we cannot yet escape.

On the other hand, a large group of scientists argued that categorizing aging as a disease with a “non-garbage” set of codes will result in new approaches and business models for addressing aging as a treatable condition, which will lead to both economic and healthcare benefits for all. This will also make it easy for researchers to conduct clinical trials as many countries strictly follow the ICD list for approvals and once a disease is recognized in this classification, it is easier for scientists to get their research funded. 

Old Age might be an ageist term, but pathological processes of aging are a major risk factor. Work on developing new and improved therapies, with the purpose of slowing and reversing the damage done by aging is thus very important.

What is now recognized?

The following list of Aging-related codes which are included in ICD-11 was curated by Daria Khaltourina. XT9T is coded for age-related and it is in combination with codes for other diseases. This long list can be useful for researchers wanting to start clinical trials in one specific domain of aging.

  • 3C0Y/Z&XT9T- Ageing-related other specified/unspecified diseases of the blood or blood-forming organs
  • 4A20.Y/Z&XT9T- Ageing-related other specified/unspecified acquired immunodeficiencies (probably the most useful for clinical trials)
  • 9E1Y/Z&XT9T- Ageing-related other specified/unspecified diseases of the visual system
  • AC0Y/Z&XT9T- Ageing-related other specified/unspecified diseases of the ear or mastoid process
  • BA00&XT9T- Ageing-related essential hypertension
  • BA01&XT9T- Ageing-related hypertensive heart disease
  • BA02&XT9T- Ageing-related hypertensive renal disease
  • DE2Y/Z&XT9T- Ageing-related other specified/unspecified diseases of the digestive system
  • CB7Z&XT9T- Ageing-related diseases of the respiratory system, 
  • BA80&XT9T- Ageing-related coronary atherosclerosis 
  • GA31.1&XT9T- Ageing-related secondary female infertility
  • 8A00.2&XT9T- Ageing-related Parkinson-like syndrome/secondary parkinsonism 
  • 8A03.3&XT9T- Ageing-related acquired ataxia, unspecified 
  • FA01&XT9T- Ageing-related osteoarthritis of the knee 
  • 2F34&XT9T- Ageing-related benign neoplasm of male genital organs 
  • GB04.Z&XT9T- Ageing-related male infertility, unspecified.
  • EE40.31- Age-related skin fragility
  • EJ20- Photoaging of the skin
  • MB21.0- Age-associated cognitive decline
  • EE40.Y- Other specified atrophy or degeneration of dermal or subcutaneous connective tissue
  • 9B10.0- Age-related cataract
  • 9B75.0- Age-related macular degeneration
  • MG2A- Old age Ageing-related decline of intrinsic capacity

Conclusion

ICD is important as it provides a common framework for recording and monitoring diseases universally between different countries, regions, and hospitals. This makes it easy to share and analysis of this data globally. 

The WHO felt that “dialogue helped to find a way forward in this matter” and allocated a dedicated process for review of the term “old age” The review led to the retraction of the term “old age” as a category title and index listings from ICD-11, having been replaced by “aging-associated decline in intrinsic capacity”. Additionally, the use of the term “pathological” as an extension code (XT9T) to describe the normal process of “aging” has been replaced by the much more appropriate term, “biological”.

This inclusion was accomplished in large measure thanks to longevity advocacy, in particular, the years-long advocacy of the International Longevity Alliance and its core activists.

So, aging is now in the ICD and can be officially addressed as a medical condition. 


The good news of the month: Aubrey de Grey’s announces rejuvenation trials on mice


The famous biogerontologist Aubrey de Grey’s was interviewed by Phil Newman, Editor-in-Chief of Longevity.Technology. He announced his new foundation will start « rejuvenation trials » on mice.

Innovative combined interventions on 18-month-old mice should be launched. The goal is to double the remaining life span.

This is excellent news. If successful, this type of experimentation offers perfect proof of the effectiveness of longevity therapy in an animal model. 


For more information

HEALES MONTHLY LETTER. THE DEATH OF DEATH No. 162. SEPTEMBER 2022. DIGITAL TWINS FOR RESILIENCE AND LONGEVITY

It’s quite possible that some people living today don’t see any upper limit (of life span). And it’s quite possible that some of us in this conversation today see 150, 200 years. And by that time (…) our technology will be so advanced that it will just keep going. George Church . Geneticist. Longevity Mindset: Proof of Age Reversal. October 2020.


Theme of the month: Digital twins for resilience and longevity


A digital twin is defined as a set of virtual information constructs that mimic the structure, context, and behavior of an individual or unique physical asset, which is dynamically updated with data from its physical twin throughout its lifecycle, and ultimately informs for decisions . It is a virtual representation of a physical asset and encompasses the entire connected product life cycle.

 Its value derives from the ability to move work from a physical to a virtual or digital environment and the ability to predict the state in the future, or when it is not physically desirable, by exploiting the digital model

In health research, for a virtual double to be useful, it is necessary that enough data from the physical person is available. In addition to all markers that change a little or not at all (height, weight, blood type…) it is also important to have social and behavioral indicators (work, diet,…) as well for which wearable devices are extremely useful. Eventually, minimally invasive sensors, both internal and external, could be envisaged to measure, for example, digestion, breathing, excretions…

Three-dimensional modeling can be used to visualize the digital companions. Once the system has been verified, computer simulations of health situations and comparisons are possible.

 Possible applications for the individuals themselves

  • Decision support for diagnosis and treatment
  • Patient monitoring by wearable devices with « projection » of future consequences, e.g., abnormal heartbeats predictive of cardiac arrest.
  • Surgical simulation – surgical risk assessment
  • Simulation of the effects of changes in medication intake, exercise, etc.

Possible applications in the fields of research

One of the major reasons why we only have a very imperfect understanding of human biological mechanisms, including those of senescence, is the lack of data available to researchers. Note that it is not the lack of data itself that makes observation difficult,  but the lack of shared data.

Comparative analysis of data from digital twins could save many patients. However, this improvement can not be achieved without changing attitudes concerning sharing data.

The first challenge is privacy. In theory, regulations and general principles of law in the European Union and in many other countries allow the use of individuals’ health data for public health purposes. In practice, this is rarely the case. It is absurd and contrary to the fundamental right to a healthy life, that access to health data is, in law or in fact, impossible. It is worth noting that almost no one disputes that data for tax purposes should be accessible to tax officials.

The « ideal » conditions for making digital twin data useful would be:

  1. Data recording using methods that allow for comparison. Ideally, at least some of the parameters should be measured everywhere by methods that give exactly the same results.

  2. Good « data curation ». This is the « cleaning » or correction of the incorrect data. It is a complex mechanism, because both « weak signals » and « abnormal signals » can be due to a measurement error or show an unexpected health phenomenon.

  3. Digital twin data is legally a common good. It can only be accessed by accredited persons and only for medical and research purposes. Use for anything else other than scientific purposes could be criminally punishable.

  4. For scientific research, a system of security, anonymization or pseudonymization would be instituted whenever technically possible. For example, data could be made available only to scientists with strict guarantees that the results of the research will be published and not patented. It should be noted that in some ways, a system where access to data is almost exclusively via your digital twin is more secure against illegitimate use than a doctor’s file. Indeed, any « entry » into the system can be traced without the possibility of « sneaking a look ».

  5. Obviously, protection against cybercrime is a fundamental issue. Even if it is a little less sensitive than bank protection (fewer people are interested in your diabetes than in your wallet!), your health is more valuable than your wallet.

The study of digital twins would allow to:

  1. To choose more adequate treatments according to specific situations, i.e. by taking into account « numerical twins » having similar conditions for many parameters like age, sex, medical past and present, diet, exercise, geographical and social environment, exposure to toxic substances,…

  2. Determine more precisely which clinical trials should be prioritized and  for which audiences.

  3.  Determine from weak signals and « surprising » elements (serendipity), research avenues that have not been yet sufficiently explored.

  4. Conduct the first tests on computer models (digital twins of existing people), largely replacing both animal and clinical tests.

Conclusion

To date, except in cases of serious health deterioration, few citizens are constantly monitored for their health. As we are increasingly monitored by numerous electronic devices, a digital twin could become both a guardian angel for each of us and a contribution to health progress for all.


The good news of the month: Singapore aims for 5 more years of healthy life


It is one of the states in the world with the highest life expectancy. The NUHS Centre for Healthy Longevity in Singapore, where two brilliant researchers, Andrea Maier and Brian Kennedy, are working, aims to increase healthy life expectancy by five years, with the first improvements appearing in three to five years.


For more information

Heales Monthly Letter. The Death of Death N°161. August 2022. Effects of aging on the bone system.

I decided early on that aging was bad for you. It made people sick and then they died. It seems so simple and so true. Why do you think many people still don’t take seriously the idea that aging can and should be fought?

People are easily intimidated by scientific information. They get a lot of it, and most of it comes from people who think about aging in a way that appeals to fantasy and wishful thinking. Public figures who talk about aging usually make things up and make a big deal about it, without detailed evidence to back up their words. This makes intelligent people skeptical, and it’s harder for people who actually have information to rise above that in terms of clarity. Richard Miller, gerontologist. May 2022.


Theme of the month: Effects of aging on the bone system


Introduction

The bones forming the skeleton, especially the skull, are a symbol of death in many cultures. They are also the last parts of ourselves that will remain, in case of burial, for decades, centuries, millennia,… Finally, the degradation of our bones is also one of the many causes of mortality due to aging.

Definition

The bone system ensures the protection of the internal organs as well as their maintenance. It also serves as a lever for the muscles to allow numerous movements.

The human skeleton is composed of 206 bones in adult life. The skeletal system is made up of cartilage, joints and ligaments in addition to bones.

It represents on average 20% of the body mass. The bones are rigid, but the skeleton is very flexible.

Bone consists mainly of collagen fibers and an inorganic bone mineral in the form of small crystals and between 10% and 20% water.

Changes with age

The aging of the musculoskeletal system is important because it affects one of the major factors of functional independence. It represents 75% of the major health problems of people over 75 years old.

With age, the mineral density of the bones begins to decrease, this is called osteoporosis. The bones lose calcium and other minerals. This loss of bone density accelerates with age, especially in women after menopause.

The spine becomes shorter as the spinal discs gradually lose fluid and become thinner. It becomes curved and compressed.

The long bones of the arms and legs are more fragile due to mineral loss, but they do not change in length. This makes the arms and legs longer than the shortened trunk.

Moreover, as we age, the cartilage inside the joints and its components deteriorate, making them less resistant and more vulnerable to injury. The aging of articular cartilage is dependent on multiple morpho-genetic factors, but also on obesity and repeated microtrauma caused by work or sport. Unfortunately, articular cartilage does not regenerate and this is why prosthetic joint replacement surgery has become so common in both the hip and knee.

Aging also affects the muscles. There is a loss of muscle, called sarcopenia (subject of our monthly letter of January 2022). During this process, the mass of muscle tissue as well as the number and size of muscle fibers progressively decrease.

The effects of these changes

The bones become more fragile, smaller and more brittle.

Joint degradation can lead to inflammation, pain, stiffness and even deformity. Joint changes affect almost all older people.

The result of sarcopenia is a progressive loss of muscle mass and strength. Movement slows down and may become limited. This loss of muscle strength increases the strain on certain joints (such as the knees) and may predispose the person to arthritis or a fall.

Common conditions
Osteoporosis is a common problem, especially in older women. Bones break more easily. Compression fractures of the vertebrae can cause pain and reduced mobility.

Muscle weakness contributes to fatigue, lack of energy and reduced activity tolerance. Joint problems, ranging from mild stiffness to debilitating arthritis (osteoarthritis), are very common.

The risk of injury increases as changes in gait, instability and loss of balance can lead to falls. Falls often result in fractures and the likelihood of death in the elderly. Fracture of the femoral neck is particularly common as a cause of death.

Involuntary movements (muscle tremors and fine movements called fasciculations) are more common in older people. Older people who are not active may have abnormal sensations (paresthesias).

Solutions to prevent the consequences of bone aging
Physical exercise is one of the best solutions to slow down or prevent muscle, joint and bone problems. Exercise helps bones stay strong.

A balanced diet also plays an important role. Especially for women, who need to take special care to get enough calcium and vitamin D as they age.

Curative solutions

There are few new therapies aimed at increasing the longevity of the bone system. However, medical treatments do exist. They act on bone cells by stimulating their reconstruction by osteoblasts. An alternative could be the use of stem cells.

However, these issues are rarely addressed, even in the longevity community. We still have much room for research and rejuvenation in this area.


The good news of the month: Mammal death is a partially reversible phenomenon


Scientists at the German University of Bochum have found that blood markers of Alzheimer’s disease are visible up to 17 years before the onset of the disease. These are biomarkers of amyloid-beta protein indicating misfolding.

If this study is confirmed, it is doubly positive. It means that it is long. Window of opportunity to counteract what triggers the disease before it becomes disabling. It also confirms the traditional hypothesis of the origin of the disease.

In this case, it will of course remain to establish the therapy that will succeed in stopping the development of « harmful » proteins and, by a cascade reaction, stop the disease.


For more information

Heales Monthly Letter. The Death of Death. N°160. July 2022. Nanomedicine in aging

Do you see longevity in medicine as a bipartisan issue and so do you think it can stay that way (…)?

(…) That is despite the discord between health care legislation regarding health insurance in general tends to be, I would say, a politically neutral issue. No one is immune to aging and chronic diseases that are developing, therefore these issues impact everyone, there is some order of fairness there and sometimes unwelcome fairness. 

There is broad support for advances in this area. The polls that you did earlier this year show that. I think 73% of those polled believe that human lifespan should continue to increase if advances in medicine and technology allow. A strong majority also approve research into the causes of cellular aging to better treat chronic diseases. 

Paul Tonko, Congressman of the 20th district of New York , A4LI Policy Discussion, 29 juin 2022.


Theme of the month: Nanomedicine in aging


Nanoscience and nanotechnology (NST) can be described as all investigations and procedures for the fabrication and manipulation of physical, chemical or biological structures, materials devices and systems at the nanoscale. 

The National Nanotechnology Initiative defines it as the manipulation of matter with at least one dimension sized from 1 to 100 nanometers.

Nanomedicine

Nanomedicine is the application of nanotechnology in the field of medicine. The term appeared in 1999 with a first mention by the American scientist Robert A. Freitas Jr. in his book Nanomedicine: basic capabilities. 

Although nanomedicine is still in its basic stage, some applications have been made in medical practice, among them, we can mention: biosensors, medications, diagnostics tools, gene Therapy ,  development of nanocapsules to aid in cancer treatment, and nanobots

Applications and uses of nanomedicine in medical field and aging research

Nano biosensors

Our body is a sum of biological and biochemical processes. The aging process is made of a deterioration and unpaired in those mechanisms. However , it is difficult to analyze biological data as an electrical signal. 

Recent advances in biomanufacturing technology may allow sensors to achieve the required high spatial sensitivity and bring us closer to realizing devices with such potential, which would truly benefit medical diagnosis. Therefore, nanobiosensors could achieve such capacity.

A biosensor is an analytical device that incorporates a biologically active element with a suitable physical transducer to generate a measurable signal proportional to the concentration of chemical species in any sample. Such a device is ideally capable of a continuous and reversible response and should not be harmful to the sample used. The term « nanosensor » refers to a system in which at least one of the nanostructures is used to detect gases, chemicals, biological agents, electric fields, light, heat, etc. Nanobiosensors are sensors in which the detectors are biological elements..

Nanobiosensors are devices designed to detect a specific biological analyte by converting a biological entity (protein, DNA, RNA) into an electrical signal that can be detected and analyzed.

The nanobiosensors may be seen as sophisticated laboratory machines capable  of rapid, accurate and  convenient measurement of complex biological interaction.

Their potential has been used for rapid detection of autoimmune diseases which could significantly prevent irreversible tissue damages and increase the quality of life in these patients. As it is also well known, the biology of cellular senescence is one of the important topics in aging research. The use of biosensors to measure, monitoring of individual living cells  could simplify the study of individual living cells and be useful for research on cellular senescence. 

Other characteristics of biosensors are that they are able to  distinguish multiple analytes  in  a single sample and detect analytes in solution at very low concentrations.

One another use of biosensors at molecular level is the DNA nanobiosensors which provide powerful tools for rapid and sensitive determination of pathogens, diseases, genetic disorders, drug screening, and other in vitro diagnostics applications. They allow an early diagnosis, even before the appearance of clinical symptoms.

 Nanotechnology and gene therapy in aging research

Various anti-aging studies in models show that gene therapy has been useful in extending the lifespan of an organism. Various genetic interventions, including mutation, knock-out and overexpression, have been shown to extend the lifespan of some animals. 

But now let’s talk about gene therapy in humans and the influence of nanotechnology on it and how it can benefit aging research.

Gene therapy consists in genetically modifying genes for therapeutic purposes. Initially, gene therapy was intended to replace a pathogenic gene in monogenic diseases, i.e. those linked to the dysfunction of a single gene. It consisted of delivering to the cells a healthy gene capable of replacing the sick gene. With new advances, other applications have emerged such as the inactivation or elimination or repair of a pathogenic gene that does not function properly. It can be performed directly in the human body (in vivo) or the cells can be genetically modified in a laboratory and then reinjected into the patient (ex-vivo).

There are a variety of types of gene therapy products, including: Plasmid DNA; Viral vectors; Bacterial vectors; genome editing technology; Patient-derived cellular gene therapy products.

Nanotechnology has advanced gene therapy through the development of nanoparticles as gene therapy carriers. Nanoparticles made up of artificial polymers, proteins, polysaccharides and lipids have been developed for the delivery of therapeutic deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) sequences to target cancer. 

Basically biodegradable nanoparticles have been used as a capsule to deliver genes into cancer cells. Even with these nanoparticles, the displacement of DNA from the cytoplasmic membrane of cells to the nucleus remains one of the major obstacles to gene therapy. However, the implementation of nanoparticles as gene therapy vectors is one of the most prominent technologies in biomedical research due to the facility and simplicity of their synthesis and functionalization with several components, their low immunogenicity and toxicity. Their success in cancer treatment is well known. It should be further developed and used in aging research.

Nanocapsules in cancer treatment

As mentioned earlier, the use of nanoparticles has been crucial for gene therapy, and even more useful in gene therapy on cancer cells. In nanotechnology, nanoparticles are not only used to modify genes in cancer cells, but also to deliver drugs into cancer cells. 

Technically, the nanoparticles are equipped with nanocarriers that guide the ultrafine particles towards the tumor cells. The nanoparticles targeting the tumor cells are only absorbed by the latter, where they release their medicinal effect to eliminate them. For the quality mentioned in the previous paragraph, nanoparticles are actually beneficial to cells,  because they act precisely on a specific cell without damaging the surrounding tissue. In fact, the FDA has approved the use of gene therapy and cell therapy drugs in the treatment of certain cancers.

Nanobots

A nanorobot or nanobot is a robot whose components are at a nanometric scale (10-9 meters). Generally the size of nanobots lies between 1 to 100 nm. Nanorobots can be used very actively  in medicine for prior diagnosis and targeted drug-delivery for cancer, surgery, pharmacokinetics, monitoring of diabetes and biomedical instrumentation.

Another useful application of nanorobots is to cooperate in tissue cell repair after tissue injury, working with white blood cells and inflammatory cells.

Some others function of Nanorobots are:

  • Bacteria detection
  • Detect Cancer
  • Determines the Effectiveness of Drug
  • Detect Particular Chemicals
  • Deliver Cancer-Fighting Drugs
  • Clear Blocked Blood Vessels
  • Serve as Antibodies
  • Clean Up Pollution

Precise drug delivery and low side effects are some of the advantages of nanorobots. The high cost of production is one of the disadvantages. 

Conclusion

We live in difficult covid times. We do not use enough nanotechnologies to defeat this disease and we regress in some health dimensions (see below).

 But we are in an era of new discoveries with new technologies. Scientists like Eric Drexler, Richard Feynman, Robert Freitas, have believed in the progress of nanotechnology and the benefits of these advances for the world. Also research against aging could benefit from an advance catapulted with these new technologies.

Today, nanoparticles already have multiple uses in different branches of medical science. They have been analyzed for different clinical applications, such as drug carriers, gene therapy in tumors, contrast agents in imaging and diagnostic devices capable of transforming biological data into measurable electrical data. The risks and benefits have yet to be studied, but the scientific advances of nanotechnologies could be of crucial help in the medical world.


Bad news of the month


The disastrous decrease in life expectancy at world level in 2020 and 2021 has been recently confirmed by the United Nations in a document called World Population Prospects 2022.

Global life expectancy at birth fell to 71.0 years in 2021, down from 72.8 in 2019, due mostly to the impact of the coronavirus disease (COVID-19) pandemic. (…) In Central and Southern Asia and in Latin America and the Caribbean, life expectancy at birth fell by almost three years between 2019 and 2021. (…) For Bolivia (…), Botswana, Lebanon, Mexico, Oman and the Russian Federation, estimates of life expectancy at birth declined by more than 4 years between 2019 and 2021.

Health technologies still progress worldwide. However, we urgently need a larger use of those health technologies, more trusted health authorities, more use of big data for longevity and resilience in order to have health technological progress creating again a global rise in healthy life expectancy.

Other scientific news in June and July from Heales.


For more information

Heales Monthly Letter. The Death of Death. N°159. June 2022. Immune system and longevity

It is always good to have dreams, even if they never come true. We are light years away from making aging a thing of the past. Recently, this field has been receiving a flood of private capital. I think this is good, because everyone will benefit. If these companies actually make key discoveries, it will benefit society as a whole.

Do you think everyone will benefit equally? I’m sure they will. You can’t limit certain advances to benefit only a select few. They always end up being democratized and benefiting everyone. There is a limit, however. If it is a very expensive solution, it will take longer to reach the common man. But it is possible to discover something that is really effective against aging and accessible. The more money that is spent on research in this area, the better for everyone.

Vera Gorbunova, American biologist, Le Soir (French-speaking Belgian daily), 29 May 2022.


Theme of the month: Immune system and longevity


Definition

The immune system of an organism is a biological system responsible for the defense mechanisms that enable it to fight against aggression.

The immune system is extraordinarily efficient, but also extraordinarily complex. It is inherited at birth, in a state of alertness or inactive, and evolves according to the contacts it has with pathogenic agents (bacteria, viruses, parasites…) or substances foreign to the body (poison, transplant…).

The organs of the immune system are called lymphoid organs, they are found throughout the body and include the bone marrow, lymph nodes, spleen, tonsils and thymus.

Their role is to produce the cells of immunity, but also to educate these cells to recognise substances that are part of the organism (=self) and foreign substances (=non-self). This education begins during embryonic development and decreases in intensity with age, leaving cells that have been less well educated (=immuno-senescence). 

The main immune defense mechanisms: How do they work?

Inflammation is the reaction of the immune system to an aggression that may be external (infection, burns, allergy, etc.) or internal (cancerous cells) to the tissues. Faced with these aggressions, the immune system will be activated. This is called an immune response. This activation is promoted and amplified by the production of messengers (interleukins or cytokines).

The immune response is of two types, innate immunity, mediated by white blood cells (polymorphs and macrophages), and adaptive immunity, mediated by T and B lymphocytes.

It is a mechanism for the defense of the organism against infectious agents in an immediate way because it does not require cell division. These cells have the ability to recognise intruders in a non-specific manner. For example, certain white blood cells such as granulocytes and macrophages instantly eliminate the intruder by digesting it to prevent its spread. When the infection is not contained locally, specialized white blood cells called lymphocytes will come and digest the pathogen a second time.

This is a mechanism in which T cells and B cells are trained from the first years of life to recognise « self » and « non-self » cells. They function in 2 ways:

  • Or by direct cell contact which leads to the destruction of the non-self cell (= cell cytotoxicity) which is carried out by T cells.
  • Or by the production of antibodies by the B lymphocytes, which will also specifically recognise foreign « non-self » molecules.

Immune system diseases

Either the immune system is too weak: this is called immunodeficiency. This deficiency can be genetic, acquired through diseases (e.g. HIV infection) or through treatments (e.g. immunosuppressants) that reduce the immune defenses.

Or the immune system is too strong: these are called autoimmune diseases. In these diseases, the immune system attacks the « self » cells. These diseases include multiple sclerosis, diabetes and Crohn’s disease. But also the chronic inflammation called inflammaging which develops with age and in the absence of infection. It seems that inflammation is caused by a loss of control of systemic inflammation leading to a chronic overstimulation of the innate immune system.

Conditions that worsen considerably with age

It has often been explained in the Heales Monthly Letters that the three main causes of morbidity and mortality are cardiovascular diseases, cancers and neurodegenerative diseases. But immune system deficiencies also play a major role through the increase in infectious diseases, the rise of autoimmune diseases and the phenomenon known as « inflammaging ».

Morbidity and mortality are not usually due to a single cause. Diseases, somatic defenses and therapeutic treatments will usually progressively weaken our bodies, especially the immune system. The little phrase « Everything that doesn’t  kill you makes you stronger » is sometimes true (e.g. the immune system can emerge stronger), but unfortunately often false (e.g. the immune system can become exhausted or out of balance).

Infectious diseases increase with age

Due to the decreasing efficiency of the immune system, most infectious diseases are becoming more and more dangerous over the years. Every year, for example, flu epidemics claim many victims. The elderly are also much more susceptible to hospital-acquired diseases. Moreover, especially in rich countries, bacterial resistance to antibiotics is particularly prevalent among people who have taken a lot of drugs in the past.

Finally, Covid of course particularly affects the elderly. For this disease, as for other infectious diseases, the mortality is not caused mainly because they are more affected. The much higher mortality is caused by deficient immune mechanisms, a weakened overall condition and a lower positive response to therapies.

Growth of autoimmune diseases with age

Autoimmune diseases are not always age-related. But mortality from these diseases mainly affects people who are no longer young.

In an autoimmune disease, the immune system attacks the body itself (the « self », hence the root auto). More specifically, autoimmune diseases attack either a specific organ (e.g. autoimmune thyroid disease) or several organs (e.g. lupus).

Inflammaging

As the name suggests, it is an age-related excessive inflammation. As already mentioned, inflammation is basically a normal and useful mechanism of reaction against internal or external aggressions. But in inflammaging, the mechanisms occur or continue and become harmful to the body.

The mechanism of a runaway reaction that was initially useful has been particularly observed in the last two years in the context of Covid, with what has been called « cytokine storms« .

Therapeutic perspectives
In fact, all research into vaccination is research into the immune system.

There is a great deal of research into maintaining and restoring the immune system. The most interesting approaches are those that aim to ‘teach’ the immune system to do a better job of attacking anything that harms the body, including immunotherapy and especially immunotherapy against certain forms of cancer.

One of the most promising, but so far small-scale, experiments has enabled scientist Greg Fahy to strengthen the thymus, and thus the immune system, of healthy elderly volunteers.


Good news of the month: Hevolution, a billion dollars a year against age-related diseases


Hevolution’s plans have been widely reported in the world press. This foundation has a strong longevity and universalist objective: « We believe that every human being has the right to live a longer and healthier life » is mentioned in English on the homepage. It seems that thanks to the foundation, the TAME project, which aims to test the effectiveness of metformin on humans, will (finally) be launched soon.

It is not the first major organization to announce longevity research involving hundreds of millions of dollars or euros (Google Calico and Altos Labs preceded it). But it is the first organization of its kind with (semi) public capital. It is, in fact, a royal decree from Saudi Arabia that is at the origin of this organization.

Of course, Saudi Arabia is not the place that most researchers and policy makers would choose first, but renowned researchers like Nir Barzilai are already involved.


For more information

Heales Monthly Letter. The Death of Death. N°158. May 2022. Happiness and Longevity.

« Every man desires to live long, but no man wishes to be old.” Jonathan Swift, Priest, writer, 1726 (Gulliver’s travels: travels into several remote  Nations of the world)


Theme of the month: Happiness and Longevity


Introduction

This month’s newsletter is only about moderate improvements of longevity through our ways of enjoying life. Regular readers of this newsletter know only radical medical scientific progress could make lifespan far beyond our biological limits possible. But while working on this long-term goal, why not also find ways to live a bit longer and happier!

Different authors have various  descriptions of what happiness is and defining happiness has been largely subjective. Each person has their own perception of happiness. In psychology, there are two popular conceptions of happiness: hedonic and eudaimonic

On the other hand, numerous behavioral psychology studies show that each individual fluctuates around a gradient of happiness that has a maximum, a minimum and an equilibrium zone. This is the theory of the hedonic treadmill (or hedonic adaptation). Whatever happy or unhappy events we experience, we would tend to return to this equilibrium point. The question then arises whether we could raise this gradient of happiness, possibly through technology, and whether raising it could have an impact on longevity.

Hedonism happiness is achieved through experiences of pleasure and enjoyment, while eudaimonic happiness is achieved through experiences of meaning and purpose. 

A systematic review published in 2014 in the Iran Journal Public Health, concludes that happiness has a complex meaning and is composed of several factors, that can be divided into two dimensions: endogenic (biological, cognitive, personality and ethical subfactors) and exogenic (behavioral, sociocultural, economical, geographical, life events and esthetic subfactors). 

Optimizing happiness is a desirable societal goal in itself. If it helps to prolong a healthy life, it’s one more reason to focus our attention on it. Let’s look through an overview of some research literature, how the feeling of well-being and happiness can influence our longevity.

Happiness and physical health

Many investigations study the association between physical health and happiness and conversely others research study the relation between physical illness (hypertension…) and happiness.

We know through literature study that the relation between physical health and wellbeing is bidirectional. Well-being can be a protective factor in maintaining health, as a deterioration in health can also trigger an impaired in well-being. Elderly people suffering from certain diseases such as coronary heart disease, arthritis… show both increased levels of depressed mood and impaired hedonic and eudaimonic well-being. 

In an analysis of the English Longitudinal Study of Aging, eudaimonic well-being was associated with increased survival. People in the lowest wellbeing quartile died in a higher percentage during the average follow-up period of 8.5 years, compared to those in the high wellbeing quartile. Other evidence shows an association between overall hedonic, and eudaimonic well-being with successful aging. High levels of subjective well-being may boost physical health and longevity as well.

Happiness and risk of death

A research study in the United States concludes that happiness is linked to longer lives in American adults. Compared to very happy people, the risk of death during the follow-up period is 6% higher among those who are pretty happy and 14% higher among those who are not happy, after deduction of marital status, socio-economic status, census division and religious attendance. A similar conclusion has been made by the English longitudinal Study of Aging, they show that personal well-being is associated with higher survival rates, even if this relation could vary among nations.

However, How different is this relationship in other countries with different economic status?

An ecological study  that used data from 151 countries, concluded that a better sense of well-being has a strong relationship with life expectancy regardless of economic status or population size.

Based on all these elements, we can say that well-being has probably a protective role in survival. However, based on the bidirectional aspect of the described relation, It is particularly difficult to know if specifically trying to improve happiness can really be positive for healthy longevity. It is worth noting that the difficulty to distinguish cause and effect is common for many aspects of longevity. For example, studies conclude that « exercise is good for longevity ». But since sick people exercise less, this does not prove that exercise in itself is good for longevity.

Psychological Well-Being and Successful Aging

Defining successful aging is not easy, and there is still no consensus among researchers in this field. Numerous studies affirm that physical and psychosocial well-being in old age is an integral part of aging well. More investigations need to be done, but what is almost certain is that unhappiness has a negative effect on people’s health and even more on their mental health. In a cross-sectional study comparing Japanese and Korean seniors, poor physical health was found to be correlated with depressive symptoms in both groups. In fact, in psychology, psychological well-being is defined as one’s level of psychological happiness/health, encompassing life satisfaction and feelings of accomplishment. An Asiatic study concludes that activities, policies and programs that maintain or improve happiness may be beneficial for a longer life among older people. However, the amount of stress that we accumulate progressively as we grow older, and the inability to manage life adversities and stressful situations may negatively affect our health and life quality in old age. In other words, our ability to cope with stress is one of the  important determinants of longevity and quality of life.

Happiness in elderly people

Happy aging is a part of healthy aging. Some characteristics such as: Cognitive-impairment, cardiovascular disease, neuropathology, activity curtailment, stressful life events, insomnia  have been considered by researchers  as the main source of depression and a contributing factor for Anti-happiness in older people. On the other hand, engagement, sense of mastery, emotion regulation, close social network, meaning in life are considered as protective factors of depression and contributing factors of happiness in longer life. Happiness is one of the determinants for healthy aging. A recent study published in 2020 concluded that well-being was associated with age. Let’s look at what are the characteristics of happiness in elderly people.

Getting older could potentially mean: 

  • A better understanding of life 
  • A deeper appreciation of the value of life 
  • A sensation of accomplishment along with fulfillment
  • A greater capacity  to understand and handle life’s vicissitudes 
  • Less pressure and aspirations on themselves
  • A better appreciation of the present moment 
  • Less worry for the future

Of course, all those characteristics are associated with the presence of those protective factors that we mentioned previously.

Conclusion

As already mentioned, happiness plays only a moderate role in improving life span. However, it is important to explore this avenue, as long as we keep the other objectives in mind:

This being written, let’s mention these four reasons why gerontology should invest in happiness research, taken from an article by Andrew Steptoe, of the journal Gerontology.

  • Happiness is not merely the mirror of depression, anxiety or distress, but has distinct relationships with a range of outcomes, so benefits from study in itself.
  • Happiness appears to be a protective factor for morbidity and mortality; although studies are complex and take a long time to complete, there is accumulating evidence that greater happiness predicts better survival among older people independently of covariates including health status and depression.
  • Happiness has broad ramifications at older ages, being related to personal and social relationships, economic prosperity, biological risk factors, health behaviors, and time use as well as health. 
  • Happiness is malleable, and can potentially be modified in ways that will enhance the health and well-being of older people.

The good and the bad news of the month


After many investigations into the effects of transfusing materials from young animals to old animals, over recent  weeks some procedures have shown significant results.

Researchers have shown that Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain. They found that microbiota composition profiles and key species enriched are successfully transferred by fecal microbiota transplantation (FMT) between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota.  

Our second piece of good news is that it has been shown that cerebrospinal fluid (CSF) from young mice can improve memory function in older mice. A direct brain infusion of young CSF probably improves the conductivity of the neurons in aging mice, which improves the process of making and recalling memories. Infusion of a protein isolated from the CSF,  fibroblast growth factor (FGF17), has also shown similar results to restore memory in old mice. Furthermore, giving the mice an antibody that blocked Fgf17’s function impaired the rodent’s memory ability.  

Let’s move on to the not so good news.

Last month, the newsletter mentioned the very bad news of a global decrease of life expectancy in 2020 and 2021. However, the World Bank published other data. According to this major organization, in 2020, there was no decrease, but only a status quo concerning world life expectancy (precisely -0.01 %). If this study is confirmed, the situation would still be bad (first time without growth since 70 years), but less than previously stated. It is also to be noted that despite all statistics, studies, … we still have large divergences of analyses concerning the impact of the Covid-19 even for the basic information that is « how many deaths ».

Other scientific news in May from Heales. 


For more information

Online Conference: Crispr, enhancement and longevity. Is the treaty of Oviedo nocive for collective health and against the 1948 constitution of the WHO?

Online Conference on  » Crispr, enhancement and longevity. Is the treaty of Oviedo nocive for collective health and against the 1948 constitution of the WHO? »   Wednedsay May 25, 5 PM to 8 PM CET

Zoom link: https://us02web.zoom.us/meeting/register/tZwvdOmhqDMiHtZrS-0OFUy0B4IoKQ08ZJ4k

Speakers :

Sheetal Soni

Dr. Sheetal Soni is a senior lecturer in the field of Bioethics, International Law, and Intellectual Property Law. She holds LLB, LLM, and Ph.D. degrees and is an admitted Attorney of the High Court of South Africa. Her research interests are genomics and the ethics of reproduction.   She is currently assisting with the drafting of Clinical Guidelines for the Provision of Genetic Services and serves on an expert panel of the Network of African Academies of Sciences and the Academy of Sciences of South Africa.

Hervé Chneiweiss

Hervé Chneiweiss, a research director at the CNRS and the President of the Inserm Ethics Committee for medical research and health. He is also Research Director of the “Glial plasticity and brain tumors” research team and is Director of the Paris-Seine Neurosciences Laboratory (Inserm/CNRS/UPMC) at the new Paris-Seine Institute of Biology.

Bernard Baertschi

Bernard Baertschi is a senior researcher and teaching professor at the University of Geneva Institut Ethique, Histoire et Humanités, as well as a member of the Ethics Committee of Inserm (France). He is currently working on fundamental ethics, bioethics and neuroethics.

Heales Monthly Letter. The Death of Death. N°157. April 2022. Self-experimentation and longevity

« I am also happy that we can let science progress, that we can give it the means to progress. Because even if there are risks, the progress of science, we owe it a lot for the quality of our life and especially the extension of our life expectancy. And as long as we are not quite sure of what comes afterwards, we must hope that science will continue to keep us alive and in good health as long as possible here on earth ».


Pierre-Yves Maillard, Vice President of the Swiss Socialist Party, 2013.


Theme of the month: Self-experimentation and longevity


Introduction

The slow progress of medical therapies for a much longer healthy life has multiple causes: cumbersome, time-consuming and costly regulations, patents preventing knowledge sharing, lack of transparency due to privacy laws, lack of publication of results and experimentation on the elderly, and lack of trials that rigorously respect scientific principles including double-blinding. This letter examines some of the ways in which this research can be accelerated.

Definition

Self-experimentation refers to the special case of research in which the researcher performs the experiment on himself.

Also known as personal scientific research, self-experimentation is an example of participatory science since it can also be conducted by patients or people interested in their own health and well-being, as both research subjects and self-experimenters.

It should be noted that in addition to self-experimentation, in order to obtain faster results, some people carry out what is called a « Human challenge study » or « Challenge trials », i.e. experiments involving the intentional exposure of the subject to the condition being tested (e.g. voluntary exposure to viral diseases for vaccine trials).

History

Self-experimentation has been practiced for centuries. Many scientists have risked their own health to help advance medicine.

Among the pioneers of self-experimentation:

More recently, best-selling author Tim Ferriss claims to be an extreme self-experimenter. Alexander Shulgin, an American pharmacologist and chemist. He is known for creating new psychoactive chemicals. He has devoted his entire career to self-experimentation, publishing his results in widely acclaimed books. Finally, Josiah Zayner (The Odin company) is a famous biohacker who in 2016 performed a microbiome transplant including a fecal transplant, in an attempt to solve health problems (notably gastrointestinal).

The « Quantified Self » is a phenomenon born in the USA in the 2000s, which consists of using connected tools or mobile applications dedicated to health in order to measure, analyze and share personal data. Among the connected tools, there are physical activity monitors (bracelets, watches, pedometers…), sleep recorders, connected scales or mobile applications dedicated to women’s health (menstruation monitoring, pregnancy…).

Self-experimentation in the field of longevity

Liz Parrish, CEO of BioViva, is one of the most well-known self-testers. In 2015, she traveled to Colombia to become « patient zero » (= the 1st person to test) of two anti-aging therapies. These consist of two types of injections: a myostatin inhibitor to prevent age-related muscle loss; and a telomerase gene therapy to lengthen telomeres.

Some people, mostly self-taught and called biohackers, also engage in research for longevity by experimenting on themselves.

This is the case for Ken Scott, a 78-year-old longevity enthusiast who has changed his lifestyle over the past 10 years. Every three months, he injects 1 cc of amniotic exosomes and Dasatinib, an anti-cancer drug that is believed to help kill harmful senescent cells in the body.

For these experimenters, the FDA rules governing clinical trials frustrate their desire to try new medical technologies. In addition, there is also the issue of cost and time. A study conducted by the London School of Economics found that the average price to bring a drug to market was $1.3 billion. And research by BIO, found that it takes an average of 10.5 years from the time a drug is in Phase 1 of a clinical trial, i.e., the first human trial, to the time of regulatory approval.

Fortunately for biohackers, there are many cheaper and easier to access tools to measure their own medical data. For example, InsideTracker, a health monitoring company in the US, offers a complete analysis for $590 including a test on 43 blood biomarkers.

In addition, one of the most knowledgeable longevitists, named Reason, has published detailed how-to guides for self-experimentation on his Fight Aging website.

Conclusion

Self-experiments allow medical advances. With regard to aging, this is particularly desirable because most « classic » trials are done on young or very healthy subjects. What should be studied is the effect on elderly people or people in declining health.

It is important that legislative changes allow or even favor such research without delay and without any requirement other than the guarantee of truly free (i.e. financially disinterested) and informed consent.


The good news of the month but also the bad news of the global toll of the Covid-19 epidemic.


Jean-Marc Lemaître‘s new book « Guérir la vieillesse » is out. « What if old age was a disease and we could cure it? » 

A study recently published in PLOS Medicine shows that healthy life expectancy is increasing (= the number of healthy years a person lives) even for people with common chronic diseases. Holly Bennett and the other researchers wanted to determine whether this extension of life involves an increase in years with or without disability. The team analyzed data from two large population-based studies of people aged 65 or older in England. For men and women with cognitive impairment, there is an increase in the percentage of years remaining on disability for both men and women. But overall, the average number of years of disability-free life expectancy increased between 1991 and 2011. For example, women gained 2.0 years and men gained 3.7 years. 

But alongside this good news, there is unfortunately some bad news. An assessment of the impact of Covid-19 on life expectancy has been made by the American researcher P. Heuveline. This assessment is catastrophic. It is the first decrease in life expectancy in the world since 1950. This was not only the case for one year, but for two consecutive years. Global life expectancy decreased by 0.92 years between 2019 and 2020 and by another 0.72 years between 2020 and 2021. The world’s citizens have returned to the life expectancy of 10 years ago. These annual declines in life expectancy mean more than 15 million additional deaths in 2020 and 2021. Please note that this figure is still provisional. It is to be refined, but above all, there is no certainty of a return to normal. Especially if attention slackens, if the support to medical research weakens… For the longevitists of 2022, it will no longer be enough to « channel the river of progress », it will be necessary to reverse the current trend in terms of real impact on health. 

Other scientific news in April from Heales.


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