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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.

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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.

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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. 

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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.

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