Category Archives: The Death of Death

Monthly newsletter about life extension.

Monthly Newsletter, The Death of Death

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

The Death of Death

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

The Death of Death

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

The Death of Death

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

The Death of Death

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.

For more information

The Death of Death

Heales Monthly Letter. The Death of Death. N°156. March 2022. Breathing and Longevity

The longevity revolution (…) that is taking place today and (…) will change human life, probably more than any other revolution we have known in human history. (…) A number of very serious scientists are telling us about this longevity revolution.

They are not crazy American billionaires, nor delusional transhumanists. They are, for example, Jean-Claude Ameisen, who was the president of the ethics committee, who is a very serious guy. (…) I have a whole series of quotes from extraordinarily serious medical professors who say that we are in the process of experiencing this revolution of longevity.

Luc Ferry. December 2021. Meeting of the future (translation).

Theme of the month: Breathing and longevity

Introduction

In the early history of life, for over a billion years, oxygen was a violent poison for the first organisms. This was in the days of single-celled organisms, when organisms were unlikely to age.

Today, oxygen is necessary for the majority of living species. Lungs appeared in marine species at least 420 million years ago. In humans, lungs are the almost exclusive source of respiration.

In the course of a lifetime, we inhale about 300 million liters of air. One liter of air weighs just over one gram, so the 12 cubic meters we take in and breathe out each day is approximately 15 kilos of gas.

When inhaled, the air is composed mainly of nitrogen (78%) and oxygen (21%). Carbon dioxide (CO2 ) accounts for only 0.04% of the air inhaled. Oxygen is needed for the body’s metabolism, and carbon dioxide must be removed.

The exhaled air is depleted of oxygen (17%) and enriched with water vapor and CO2   (4%). On exhaling, the air is also loaded with invisible aerosols. These contain viruses and bacteria, possibly pathogenic, from the respiratory tract and the oral cavity. These aerosols contribute to the phenomenon of contagion, even in the absence of coughing and sneezing. The rate of respiratory aerosol tends to increase with age.

Unfortunately, we also absorb these organisms from our relatives as well as many other substances, such as fine particles from pollution, allergens, etc.

Breathing also allows us to use our sense of smell, the fascinating capacity of olfactory cells that allow our brain to distinguish between millions of odors based on minute quantities of volatile substances. With advancing age, these abilities, like others, imperceptibly but, until today, irreversibly diminish.

What are the main lung diseases? Three main categories

  • Acute illnesses : 

Infectious diseases of the bronchial tubes (bronchitis) or lung tissue (pneumonia). In both cases, the disease is bacterial or viral in origin. Pneumonia can also be caused by a fungus and bronchitis by irritants such as smoke.

The elderly are very vulnerable to these diseases. Aging favors the entry of infections because defenses are weaker and because there are usually other pathologies or chronic diseases present.

Bronchitis is rarely fatal but can become chronic. Pneumonia, on the other hand, can have serious consequences for an elderly person and lead to death. Nearly one in five centenarians dies from pneumonia, compared to only 6% of 80-85 year olds.

  • Chronic lung diseases including :

Asthma can develop at any age. When an older person develops asthma, the symptoms are mostly the same as those affecting younger people. However, it is more risky for an older person because they are more likely to develop other respiratory problems.

COPD (Chronic Obstructive Pulmonary Disease) is a common inflammatory disease of the bronchial tubes. It is often the result of heavy exposure to inhaled toxic substances such as tobacco or pollution. In the elderly, it often develops into a respiratory disability requiring oxygen at home.

  • Lung cancer :

Lung cancer is primarily caused by smoking, but also by exposure to substances such as asbestos or fine particle pollution. In Belgium, it is the 3rd most common cancer. Every year, more than 3000 people between 60 and 70 years old get lung cancer. The frequency of these cancers increases with age, but decreases after 70 years. It is one of the most dreaded cancers as only 18% of men and 16% of women survive more than 5 years.

Why are respiratory diseases more common in older people?

Because aging involves: 

  • Decreased muscle strength, especially in the intercostal muscles, back muscles and respiratory muscles.
  • Decreased cough strength.
  • Decreased airway clearance.
  • Decreased tissue elasticity due to degeneration of elastic fibers and changes in collagen.
  • Inflamm-age » phenomenon.
  • Changes in the immune response.
  • …

Medical advances and research

  • Antioxidants

We can first note that, especially in the past, antioxidants have been considered as a means to fight aging. The idea is that respiration generates free radicals with deleterious effects and that substances can absorb these radicals. However, this concerns respiration at the level of the cell, not specifically the lungs. Furthermore, to date, no antioxidant has demonstrated a significant and undisputed longevity effect. 

  • Gene therapy for lung disease

As far as respiratory diseases are concerned, many are chronic and often of genetic origin.

The lungs are an accessible organ for gene therapy, but the complexity of the lung structure presents certain physical and chemical barriers to the delivery of viral vectors. In addition to these barriers, symptoms such as a thick mucus layer in the case of cystic fibrosis complicate the process.

A study published in the Journal of Clinical Medicine in 2020 summarizes the various advances in gene therapy for respiratory diseases such as cystic fibrosis, alpha-1 antitrypsin deficiency (AATD) and primary ciliary dyskinesia (PCD).

In recent decades, there have been great advances in gene therapies for respiratory diseases. However, researchers are still working on new breakthroughs due to ongoing concerns about safety, specificity and efficacy.

  • Stem cells

As in most of the rest of the body, stem cells are found in the lungs. The use of stem cells for regeneration is being researched. In particular, the creation of organoids is possible, but there are no real direct applications for older humans.

  • Transplants

Lung and trachea transplants are still exceptional operations. As for other organs, xenotransplantation (organ from animals) and bioprinting (printing of tissues or organs) are also envisaged, but not yet carried out.

And further on

Here, as elsewhere, the combination of growing knowledge, coupled with broad-based commitment and funding, can lead to incremental progress and breakthroughs. For example, the catastrophic effects of covid on the respiratory system of the elderly have been rapidly reduced. This is one of the reasons for the insufficient but significant decrease in mortality from this disease.

Good news of the month:
Effective cellular reprogramming in aged mice

It was already well known that the addition of a mixture of 4 reprogramming molecules under the name « Yamanaka factors » to cells can reset epigenetic marks to their original state. This partial reprogramming over short periods of time counteracts the signs of aging and increases the lifespan of mice with premature aging disease.

In March 2022, in a paper published in Nature Aging: « In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice. « In this paper, it is found that long-term partial reprogramming leads to rejuvenation effects in different mouse tissues. And that the duration of the treatment determines the extent of the beneficial effects.

In a recent study conducted by Prof. Juan Izpisua Belmonte and his teams at the Gene Expression Laboratory of the Salk Institute for Biological Studies, researchers performed various long-term partial reprogramming regimes in healthy animals, including at different onset times, during physiological aging.

A first group of mice received regular doses of Yamanaka factors from 15 months to 22 months of age (human equivalent: +/- 50 to 70 years). A second group was treated from 12 to 22 months (human equivalent: +/- 35 to 70 years). And finally, a third group was treated for only one month at the age of 25 months (human equivalent: +/- 80 years). Unfortunately, for these experiments as for many others on rats or mice, as the animals are sacrificed at the end of the experiment to be able to analyze their physiological state, the real result in terms of maximum lifespan is not known.

Compared to control animals, there were no alterations in blood cells or neurological changes in mice that received Yamanaka factors.

The researchers claim that the rejuvenating effects are associated with a reversal of the epigenetic clock and metabolic and transcriptomic changes. The scientific team is now planning future research to analyze how specific molecules and genes are modified by long-term treatment with Yamanaka factors.

For more information:

The Death of Death

Heales Monthly Letter. The Death of Death. N°155. February 2022. Massive health data and longevity. European developments.

)(§These actions will be funded by the EU4 Health (…) and Horizon Europe programmes, with the aim that by 2025 (…) citizens in all Member States will be able to share their health data with healthcare providers and authorities of their choice (…). This extract from a Commission Communication to the European Parliament (Fostering a European approach to artificial intelligence) means, if put into practice, that every citizen will be able to share this data with scientists (with data protection guarantees, of course). This would be a very big step forward for longevity research and for health in general.

Theme of the month: Massive health data and longevity. European developments.

Introduction

Health « Big Data » is everywhere: it seems it represents 30% of the total mass of data available in the world. Today, in a country like France, almost all medical activities are at some point recorded by computer.

The issue of accessibility of health data for researchers has already been addressed in a letter of September 2020. This letter details recent developments, hopes and limitations at the level of the European public.

The hopes

The acceleration of digitalization in health during the pandemic and massive data

First of all, we are already in the era of Medicine 4.0. At the same time, as a result of government measures in the fight against the Covid-19 pandemic, the digitization of health care has accelerated worldwide: the debate about personal data for medical purposes is spreading among the population.

This pandemic has affected us so much and, at the same time, has forced us to think about public and individual health. No responsible decision-maker would want to repeat this physical and moral restriction without a scientific understanding of the causes. Therefore, many will reflect on the importance of sharing « big data » in order to obtain a faster and more efficient measurement of results, for drugs, vaccination or prevention. Finally, Covid-19 was an opportunity to realize the usefulness of sharing massive data in health.

Institutional work in the post-Covid-19 era

In this context, the European Union is taking an initiative to create a common platform between the Member States: the European Commission is considering the creation of a European Data Space including the field of health for the period 2019-2025.

In December 2021 the European Parliament and the Council of the EU announced their agreement on the Data Governance Act (GDA). This agreement aims to facilitate altruistic data practices between public and private organizations to support scientific research.

As for scientific research, a new regulation of the European Parliament and of the Council concerning clinical trials for human use, Regulation No 536-2014, came into force on 31 January 2021. It envisages the creation of a CTIS platform, Clinical Trials Information Systems. This is an optimistic first step towards sharing data for research purposes. It is only the beginning of a project that will bring about change within the European area.

Innovative state systems in the European Union

Regarding the system of sharing massive health data at state level, there are several states in the European Union that have made a platform available. For example, Denmark has had the « Medcom » system for 25 years, and in Sweden the Swedish National Data Service also exists for the re-use of data for research purposes. It is the trend towards the re-use of health data at state level that could influence other Member States.

In this context, the joint TEHDAS project for the re-use of health data brings together 25 European countries. This consortium plans to start in 2022.

The notion of data altruism

In discussions on data management in general (not only health data), some have advocated for the concept of « altruism » for organizations that would be data controllers. The idea is to create a category of organizations that present guarantees of efficient processing on the one hand, and of processing in accordance with the objectives on the other. For example, in the case of health research, this would mean that it would be inaccessible in law and in fact to insurance companies, employers, etc., but accessible to researchers.

The difficulties

The Health Data Hub in France and the RGPD

In France, the temporary failure of the Health Data Hub project (L1462-1 Code de la santé publique) became apparent in December 2021. The government’s withdrawal of its request for authorisation from the CNIL is a consequence of a political strategy before the presidential election in 2022. The choice of a suitable cloud is essential. For the sharing of massive data, this is a big obstacle.

According to the judgment of the Court of Justice of the European Union of 16 July 2020 (the Schrems II judgment), transfers of personal data from the EU are contrary to the RGPD as well as to the Charter of Fundamental Rights of the European Union. Unless there are additional measures or transfers are justified under Article 49 of the GDPR (paragraph 5: « In the absence of an adequacy decision, Union law or the law of a Member State may, on important public interest grounds, expressly set limits on the transfer of specific categories of personal data to a third country or to an international organization. »).

Therefore, the Health Data Hub project has to be postponed as announced to the end of 2021.

The Health Data Hub is also arguably something of a white elephant. Despite the nice plans to share data, the practical situation is that only a few of the hundreds of requests from scientists for access to data are successful.

Fear of influence by US giants

A European cloud project, Gaia-X, was launched in 2019, based on collaboration between France and Germany. It aims to establish an autonomous system in the face of American and Chinese competition. It provides a framework for data exchange. This gives hope, for example, to solve the problem of choosing the cloud for the Health Data Hub, as mentioned above. 

Limited EU intervention in health for Member States

Despite the existence of several programmes and work by the European institutions in the field of health data sharing, the realization of data sharing does not seem to be close. One of the causes of this difficulty is the fact that the shared competence of the European Union in health matters is limited as follows: TFEU Article 168 paragraph 4 a,b,c.

Except in these limited matters, the EU can intervene in a non-binding way even if the data shared are health-related: it is up to the Member State to decide whether to make such a measure available.

The GDPR and the limiting provisions related to privacy

In theory, the famous General Data Protection Regulation does not prevent scientific research. In practice, it is clear, particularly in times of Covid, that there is a kind of mechanism of fear mongering – sometimes not very rational – in particular towards public health authorities. This mechanism leads to a great slowness in authorisation procedures, or even refusals, with many useful research projects being delayed.

Technical difficulties

Beyond the complexities of policy decisions and privacy issues, there is a need to ensure data interoperability. This is complex, especially at the European level, as IT systems and data come from very different sources. ‘Trash in, trash out’ situations, i.e. incorrect (or incompatible) information ‘corrupting’ other data, must be avoided.

In conclusion

There are countless initiatives to share data, especially for scientific purposes.

An ideal solution would be a system:

  • Having the trust of the citizens
  • Managed by a public institution (or non-profit organization)
  • Allowing by default (opt-out) the use of all health-related data (anonymized or pseudonymized) 
  • For scientific research (not for other uses).
  • Ultimately enabling everyone to live longer and healthier lives.

The European Union is currently the most appropriate place to develop this.

Good news of the month. Major advances in xenotransplantation.

Under normal circumstances, a transplant of a pig heart or kidney into a human body leads to immediate rejection, sometimes even before the operation is completed. For the first time, these two operations have been performed on two patients. This is very promising. For more than a month, David Bennett has been living with the heart of a pig and since September 2021 another patient has been living with the kidney of a pig. To make this possible, the animals were genetically modified. This means considerable progress for gene therapy as well as for xenotransplantation. And so in what may be a short time, it is very useful for research into healthy longevity.

For more information:

The Death of Death

Heales Monthly Letter. The Death of Death. N° 154. January 2022. Sarcopenia and longevity

The law is strict on rapamycin and metformin, requiring a prescription. In comparison, alcohol and tobacco do not require a prescription or medical supervision. Smoking has no health benefits and significantly reduces life span, accelerating all diseases. While smoking causes cancer, rapamycin prevents it, including smoke-induced lung cancer. Is it not paradoxical, then, that alcohol and tobacco are sold without prescription, while rapamycin and metformin are not? The Goal of Geroscience is Life Extension. Mikhail V. Blagosklonny February 2021. (Translation)

Theme of the month: Sarcopenia and Longevity

What is sarcopenia?

With advancing age, almost everything that makes up the components of a human being or other vertebrate gradually loses its efficiency: digestive, cardiac, neurological and immune systems, skeleton, skin, etc. Muscles are no exception to the rule.

Sarcopenia (or age-related muscular dystrophy) is the age-related progressive decline in muscle mass and strength, associated with a decline in physical performance.

In 1989, the term « sarcopenia » was defined by Irwin Rosenberg, researcher and acting director of the Neuroscience and Aging Laboratory at Tufts University in the United States, to refer to the decrease in muscle mass during aging.

From what age?

From the age of 30, muscle tissue undergoes a progressive degeneration of about 3 to 8% per decade. From the age of 50 onwards, the loss of muscle quantity and strength accelerates. By the age of 70, half of the muscle mass is lost to fatty tissue. The loss of muscle mass affects all older people, including those who are healthy and active.

The causes and consequences of sarcopenia?

Several interrelated causes are involved in the development and progression of sarcopenia. These contribute to the loss of muscle mass and strength:

  • Denervation and loss of motor unit functionality is thought to result in reduced muscle fiber constructibility.
  • The effect of anabolic hormones is strongly disrupted in the course of aging. Either the concentration of circulating hormones is reduced, or the sensitivity of the muscle to the action of certain hormones such as insulin appears to be diminished.
  • Dietary proteins are no longer used efficiently by the body. As a result, the nutritional intake of the usual diet is inadequate to meet the needs of the aging body.

The risks and consequences of sarcopenia vary greatly depending on age and degree of impairment:

  • Progressive decrease in muscle strength
  • Fatigue leading to a decrease in physical activity
  • Weakness
  • Increased risk of falls and fractures
  • Increased risk of dependency and loss of quality of life.

Is it possible to slow down sarcopenia?

Some nutritional strategies combined with sufficient physical activity make this possible.

Protein pulse feeding: « this consists of providing 80% of the recommended daily protein intake in a single meal. This technique makes it possible to partially saturate splanchnic extraction (i.e. retention of dietary amino acids by the intestine and the liver for their own needs) in order to obtain better bioavailability of amino acids for the stimulation of postprandial muscle protein synthesis » (source: Wikipedia).

Citrulline (the only amino acid not taken up by the liver) and leucine both have a stimulating effect on muscle protein synthesis through their action on the mTor pathway. They are therefore good strategies for combating sarcopenia.

In addition, in order to reduce muscle loss as well as for the proper functioning of the rest of the metabolism, sufficient physical activity must be combined with the nutritional strategy.

What is the state of scientific research on sarcopenia?

In December 2021 laboratory-grown human muscle cells were launched into space in an experiment conducted by the University of Liverpool.

This study, called MicroAge, aims to monitor the growth of muscle cells in microgravity and help understand why the body weakens with age.

At the end of the experiment in January 2022, the muscles will be frozen and returned to Earth where scientists will undertake further analysis.

The relationship between sarcopenia and cardiovascular disease 

Both sarcopenia and cardiovascular disease are accelerated by the chronic inflammation of aging, but the onset of physical weakness resulting from sarcopenia can also contribute to cardiovascular disease through reduced physical activity.

Changes in lean body mass are common critical determinants in the pathophysiology and progression of cardiovascular disease (CVD). Sarcopenia can induce CVD through common pathogenic pathways such as malnutrition, physical inactivity, insulin resistance and inflammation; these mechanisms interact. 

Sarcopenia and CVD are widespread in the elderly and share common pathogenesis and interactions. The understanding of their relationship is still in its infancy, and more clinical and experimental data are needed. 

A large number of studies have shown that the progression of CVD and the decline in muscle function worsens the condition of patients. By screening for sarcopenia at an early stage, with effective detection and assessment methods in place, it is possible to effectively delay the progression of the disease.

Sarcopenia and gene therapy

In 2015, Elizabeth Parrish underwent a – controversial – gene therapy with telomerase and follistatin as part of the creation of the startup BioViva. In the case of follistatin, the aim is to directly suppress myostatin or to enhance follistatin to suppress myostatin. This has the effect of increasing muscle mass and reducing fatty tissue, while adapting the functioning of the metabolism to a healthier mode of functioning.

These injections consist of a myostatin inhibitor to protect against the loss of muscle mass with age.

After further examination and testing, comparison of Parrish’s pre-therapy and post-therapy data revealed additional positive changes.

And tomorrow?

As written at the beginning of this letter, with age, almost everything that constitutes the organic components of a human being or any other vertebrate gradually loses its efficiency. But the rate of loss varies greatly depending on the tissue: from 1 to 1000, from a few weeks to a few centuries. The future, thanks to the progress of knowledge already underway, may consist in doing at least as well, sustainably and … muscularly as the longest-lived species.

Good news of the month

The World Health Organisation (WHO) maintains the International Classification of Diseases (ICD), which is revised regularly. 

ICD-11 officially came into effect on 1ᵉʳ January 2022 (although implementation of ICD-11 may not begin for several years.

Unlike previous versions, ICD-11 allows for a variety of synonymic interpretations, including those that may be very useful to a clinician treating older people, such as « aging », « senescence », « senile state », « frailty » and « senile dysfunction », which refer to a health condition. The new classification includes the code « age-related » in the etiology or causality category to target the pathogenic processes of aging.

Some have suggested that the code « old age » should be excluded from the latest version of the International Classification of Diseases, ICD-11, on the grounds that treating old age as a disease could have the negative consequence of treating civil age as a disease.

Yet, far from discriminating against the rights of older people and encouraging neglect of their curative or preventive health care, the ICD-11 codes for old age and age-related causation do exactly the opposite: they draw public and professional attention to the specific health problems of older people and call for action to improve prevention and treatment specific to them.

For more information:

The Death of Death

Heales Monthly Letter. The Death of Death. N° 153. December 2021. If humans didn’t die of old age, would we regret it?

Imagine a rather educated mouse asking himself if it is theoretically possible to live more than two and a half years his average life expectancy? Of course, it is possible, she would say, look at the human species (…), mammals like us that live thirty to forty times longer! Beyond our biological limits: The secrets of longevity. 2011. Miroslav Radman.

Theme of the month: If humans didn’t die of old age, would we regret it?


Introduction
Let’s imagine a world not so different from ours. However, humans and most animals would not experience aging.

In this world, would we wish senescence, that is, the progressive degradation until death, on ourselves and our children?

Let’s imagine, for example, a biological environment a little more « Lamarckian » than the one we live in. In epigenetic evolutions, acquired characteristics would be more transmissible. An older animal would have, as here, advantages in terms of experience. Moreover, the descendants would benefit from an increased transmission of acquired characteristics. In this case, natural selection would have less « need » for senescence, since the evolution of species could occur because of changes during the life of individuals. Let us imagine that the probability of dying of natural causes is therefore relatively stable, from one year to the next, once the adult age is reached. Let’s imagine a planet with no aging death (and also no aging degradation) for most living species.

For the rest, the « laws of nature » would apply: selection of the most adapted, evolution of preys, predators and parasites, competition and cooperation between animals, plants, bacteria, fungi… Animals would live longer, without aging, but would still die from all other causes. Biological immortality is not the same as immortality.

A world without aging would not be paradisaical but…
Obviously, it is impossible to imagine all the consequences. Let’s focus on humans. Theoretically, some could live for thousands of years. But this would be extremely rare before the development of civilizations because epidemics, predation, violence would strike all individuals.

But once civilizations appeared, the environment would be radically different. The accumulation of knowledge would be faster, philosophers, scientists, leaders could be influential for centuries. Religions would exist, but they would logically be more peaceful, less focused on the afterlife, more concerned with bodies and souls here than with the afterlife.

Soon enough, in the more prosperous regions, birth control would expand. Soon enough, science and medicine could focus more on preventable causes of death. Indeed, the positive stakes of disease control would be higher, there would be more years of life to gain.

As for these humans, the capacities would not decrease with age, the mechanisms of nostalgia, of withdrawal to the past, would be less. Indeed, nostalgia is often the regret of youth following the loss of energy, health, taste, other senses… Nostalgia following the loss of loved ones would also diminish. 

In our contemporary world, philosophy is sometimes defined as « learning to die » (and to die quickly). Where death would no longer be inevitable, at least on the scale of centuries, philosophy would be more about learning to live, learning to respect others and oneself. In a more stable world, the need for an environmental balance is more obvious.

Advancing age would be, as in our world, synonymous with wisdom. It would be a wisdom with less bitterness and regret of the past and therefore more openness to the future.

In this place where death is no longer inevitable and is becoming rare thanks to technological and medical progress, it is possible to imagine that any death inflicted, any murder, would not only be unacceptable, it would become unimaginable. Just as today killing a child is almost unimaginable, because he has « his whole life ahead of him », whereas in the past infanticide was often tolerated and sometimes totally accepted, especially because many children died in infancy.

In a world without age-related degradation, would we invent aging?
Some philosophers, some religious leaders might want the older ones to disappear. Some might say that it is necessary to renew the population, to have children without the risk of overpopulation.

Would the representatives of this current of thought want to kill the most advanced people in age? And if so, create a system where death is slow, insidious, progressive, painful, ineluctable… rather than, for example, creating compulsory euthanasia for some?

This seems unlikely in a world of less violence. Already today, even the most bloodthirsty regimes no longer (almost?) officially practice torture as a means of pressure. So inflicting aging and then death …

What if the glass was half full?
Let’s finally imagine an environment where humans are not amortal, but live twice as long once they are adults. The prime of life would be at 100 years and Jeanne Calment would have lived 245 years.

No one would likely propose ending life after 80 or 90. It is the situation well beyond that which would be « normal » and would appear to almost everyone as desirable… until the situation changes.

Just as no one today proposes to end life at age 50, when that was the « normal » maximum lifespan for most of human history.

Conclusion
If aging did not exist, we would not have to invent it. All other things being equal, we probably wouldn’t consider it, even for our worst enemy. We would not wish for years and sometimes decades of unbearable degradation ending in death.

Moreover, if we lived in a world without aging, not only human life, but also the lives of sentient beings (capable of suffering) would be far more precious. Even the most disrespectful of individuals, raised in this universe, would have difficulty imagining inflicting the torments of an endless torture called aging. Just as today, even a violent recidivist thief would probably not think of burning the feet of an elderly person to make him confess where his money is, and then murdering him, a common practice in France and elsewhere until the early 19ᵉ century.

Aging is now inevitable. We have already managed to humanize it considerably. We are also managing to slow it down a bit. Tomorrow we may be able to stop it. In all likelihood, we will not regret it any more than we regret the eradication of the plague and cholera.

Good news of the month

  • Japanese scientists develop a vaccine to eliminate cells responsible for aging. The team, including Toru Minamino, a professor at Juntendo University, confirmed that mice given the vaccine had a decrease in the number of zombie cells, known medically as senescent cells. The team identified a protein found in senescent cells in humans and mice and created a peptide vaccine based on an amino acid that constitutes the protein. This news has received significant media coverage. It is part of the many hopes for senolytic products. However, the experiment concerns only mice. Moreover, the maximum life expectancy was verified on « progeroid » mice (with a much shorter life span), but not on « normal » mice.
  • The first clinical trial of a nasal vaccine for Alzheimer’s disease began in Boston. The vaccine, formulated from an immune-boosting substance (Protollin), is intended to prevent and slow the progression of Alzheimer’s disease, the disease associated with aging for which medical research has been slowest… A Phase 1 trial involves 16 participants, aged 60 to 85, all with early-stage Alzheimer’s disease but in good general health. They will receive two doses of the vaccine. The research team will measure the effect of nasal Protollin on the immune response, particularly its effect on white blood cells, by examining cell surface markers, genetic profiles and functional tests.

For more information:

The Death of Death

Recent developments in gene therapies for longevity. Heales Monthly Letter The Death of Death. November 2021.

John Harris, former editor of the Journal of Medical Ethics, argues that as long as life is worth living, according to the individual, we have a powerful moral imperative to save life and therefore to develop and offer life-prolonging therapies to those who want them (Source). 

Theme of the month: Recent developments in gene therapies for longevity

Introduction 

The average lifespan of both animals and humans varies according to many factors. For animals,  diet, predation, disease and  climatic conditions play the most important roles. In humans, lifestyle, disease and social conditions are the determining factors.

But when it comes to the maximum lifespan of animals, like that of humans, the most important element is the genetic heritage. 

We still know very little about the genetic differences that favour or hinder longevity in humans. Studies of genetic characteristics related to longevity have been conducted, including studies of supercentenarians.  Although genes such as the klotho gene are sometimes cited, no single gene or group of genes appears to have a very strong positive influence.

A human being who lives in a perfect environment with adequate health care and an exemplary lifestyle would never live past the age of 122. It should be noted that the oldest person in the world has been a woman for almost 40 years, which can be explained by the genetic difference between men and women. 

Place a mouse in a mouse paradise. No matter what happens, it won’t live past five years. Place a Galapagos tortoise in a chelonian paradise and it will live at most two centuries.

Very similar animals can have very different maximum life spans. For example, the Labord’s chameleon of Madagascar is the terrestrial vertebrate with the shortest life span. It lives only 4 or 5 months. While its distant cousin from the same big island, Parson’s Chameleon, can live for about ten years.

In other words, we know that few genetic modifications can allow considerable changes in lifespan.

This is one of the reasons why gene therapies are among the most promising therapies for longevity.

What is gene therapy? 

Gene therapy is one of the preferred ways to treat genetic diseases, but also certain cancers. It consists of inserting into the patient’s cells a normal version of a gene that does not work and causes the disease. 

The functional gene then allows the patient to produce again the protein whose deficiency was the source of the disease.

However, three conditions must be met: 

  • Knowing the gene responsible for the disease, i.e. the function of that gene, so that the cell can be « repaired ».
  • Allowing the gene to reach and enter the cell with the help of a « vector », most often a virus that has been rendered harmless to the patient.
  • And associate the gene with a « promoter », a small DNA sequence that allows it to function once inside the cell.

It is also possible to transform the genetic heritage of subsequent generations. It is conceivable that one day our children could live longer and healthier lives as a result of genetic modification. This raises innumerable ethical questions, some of which have been addressed by the birth of two (or perhaps three) genetically modified babies in China. These issues will not be discussed here.

The gene therapy revolution

In 2000, for the first time in the world, gene therapy demonstrated its effectiveness with bubble babies, children with severe immune deficiency who returned to normal life with the treatment. However, the therapies were slowed down and then virtually halted for more than a decade following the deaths of two patients, including Jesse Gelsinger. However, during this interruption countless lives could have been saved.

Between 2015 and 2020, gene therapy has experienced a considerable boom. Several clinical trials have been conducted to treat certain blood, skin and neuromuscular diseases. Some of these trials have been sufficiently successful to lead to market authorization in the United States and Europe. 

In 2017, a team of European doctors managed to replace 80% of a little boy’s epidermis (suffering from epidermolysis bullosa) with gene therapy.

By 2019, about ten gene therapy treatments for rare blood, vision, muscle and certain cancers had received marketing approval in the United States or Europe.

In the same year, the first gene therapy drug (Zolgensma) capable of saving the lives of babies with diseases such as spinal muscular atrophy was put on the US market. 

Other treatments for Pompe disease, adenosine deaminase deficiency, beta-thalassemia, acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and Leber’s amaurosis have been developed.

However, treatments are still usually aimed at uncommon diseases, generally linked to an « error » in a single gene.

Gene therapy and longevity: Can it delay or reverse age-related diseases including neurodegenerative diseases?

In 2019, a study by George Church and his teams showed favorable results of a therapy acting simultaneously on three genes in mice with various age-related symptoms.

In the same year, an experiment on a gene for telomeres was carried out by researchers from the Chinese Academy of Sciences on mice in 2019. This resulted in a longer life expectancy.

In 2020, mRNA vaccines were used to induce immunity against COVID-19. This method is similar to gene therapy. However, the changes concern the RNA and not the DNA. 

In October 2021, BioViva, a biotechnology startup led by E. Parrish, demonstrated that by administering gene therapy to six patients with dementia that a reversal of dementia symptoms such as cognitive impairment could be observed. 

The American Elizabeth Parrish is also the first known case of self-testing of a gene therapy targeting ageing processes. The treatment consists of injections of adenovirus, which could extend leukocyte telomeres and thus strengthen muscle mass.

Conclusion

A massive sharing of knowledge, including statistics, about genetic endowments is developing. Investments for a longer healthy life seem to accelerate and improve. The European Union is proposing legislative tools for « altruistic » databases. 

Billions of sequencings (total or partial) have been performed on animals, plants and humans. The pooling of these data and their analysis, in particular by means of tools based on artificial intelligence, is continuing. Thanks to genetic modification technologies such as CRISPR, it should be possible to break through the « glass ceiling » of the maximum lifespan for mice and then for humans in the near future.

The good news of the month

The European Longevity Initiative was launched by a non-governmental organization with members in some 20 EU countries.

Its proposal was the most supported of the Conference on the Future of Europe and is still one of the most supported.

The main promoter of the idea is the Hungarian scientist Attila Csordas, who said:  » The only real solution (for many, many diseases) is to start treating the root causes of biological aging (…). We have experimental strategies to slow down the rate of accelerated aging and reduce morbidity and mortality in late life. To achieve this in the European Union, we would like to propose effective legal, budgetary, regulatory and institutional commitments to enable science-intensive healthy longevity research and technologies, large-scale geroprotective clinical trials focused on ageing and equitable access to these technologies to increase healthy life expectancy in the European Union.”  

The European Health Data Space is at the centre of many projects aimed at better exchange of health data for medical and research purposes. An international conference on 19 November on « Innovations in Consumer Longevity Data » is one example. 

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