Category Archives: Monthly Newsletter

Monthly Newsletter, The Death of Death

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

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

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

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

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

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

Is aging a disease for the ICD?

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

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

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

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

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

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

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

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

What is now recognized?

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

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

Conclusion

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

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

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

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

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

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

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

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

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Monthly Newsletter, The Death of Death

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

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

Theme of the month: Digital twins for resilience and longevity

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

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

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

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

 Possible applications for the individuals themselves

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

Possible applications in the fields of research

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

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

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

The “ideal” conditions for making digital twin data useful would be:

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

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

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

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

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

The study of digital twins would allow to:

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

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

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

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

Conclusion

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

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

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

For more information

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.

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