Commentary on Old Age in the International Classification of Diseases

The world of medicine and medical research is regulated to the point of extreme dysfunction. Regulation determines the flows of funding in the clinic, which in turn determines priorities for research and development. To swim against the tide is significantly harder than to go along with it, and this has a material effect on the speed with which the scientific community and biotech and pharmaceutical industries can create and deploy therapies to treat aging. Even the prospect of treating aging as a medical condition at all is shadowed by the way in which regulation distorts the playing field. Yes, a working, proven rejuvenation therapy will ensure its own success, and all positions will rapidly adjust to the new reality, but getting to the point of making such a therapy, and getting to the point of proving it sufficiently well to convince the world, is made significantly harder by the perverse incentives of medical regulation.

Today, I'll point out a little of the ongoing commentary surrounding one of the most bureaucratic, slowest aspects of medical regulation, the periodically updated International Classification of Diseases (ICD), now up to version ICD11. The ICD is relevant because much of the developed world bases their medical regulation on the classifications in the ICD. If a condition is not included in the ICD in a usefully explicit way, then the barriers to gaining approval for a therapy are very high indeed. That in turn shapes all of the research and development priorities leading up the creation of new therapies. The ICD is managed by the World Health Organization (WHO), a body that exemplifies the traits of large bureaucracy to the point of self-parody. For example, as the first commentary indicates, avoiding the appearance of ageism is a somewhat higher priority than encouraging development of means to treat aging in order to reduce late life suffering and mortality.

None of this is ideal, and at present most biotech startups in the longevity industry are doing their best to avoid the whole situation by devoting their efforts towards treating specific defined conditions of aging, rather than aging in general. That has its own disadvantages when it comes to turning science into treatments that are broadly rather than narrowly beneficial. It leads me to the belief that the best way forward, in the bigger picture, is to use philanthropic funding to pay for clinical trials that produce compelling demonstrations of human rejuvenation, compelling enough to shake up the regulatory system. At the present time, I think that the fastest path to this outcome is to show the world, beyond a doubt, that senolytic treatments can rejuvenate the old, and that the very impressive results achieved in aged mice can be replicated in humans.

How "old age" was withdrawn as a diagnosis from ICD-11

WHO had proposed the inclusion of the term "old age" in ICD-11. Ageing is not a pathological process and is globally accepted as a normal human attribute, with longevity being a privilege that we all hope to enjoy. The new "old age" label in ICD-11 was intended to replace the R54 code of "senility", previously used in ICD version. The decision to replace the R54 code resulted from increasingly negative connotations around the term "senility". An additional extension code (XT9T) was included in the causality section of ICD-11, which defined "ageing-related" as "caused by pathological processes which persistently lead to the loss of organism's adaptation and progress in older ages". The intention for including the additional code was to provide a greater focus on the biological aspects of ageing in global health policy and better opportunities for the development of new biological therapies. However, because of societal ageism, and because biological ageing and chronological ageing are not synonymous, the addition of these two codes left the ICD-11 proposal with potential for unintended negative consequences.

To be clear, WHO's inclusion of "old age" in ICD-11 was not intended to cast age or ageing as a disease, nor to consider ageing in terms of the number of years since birth, or greater than a particular age category. The intention was to recognise that the physiological process of ageing has a detrimental effect on a person's intrinsic capacity. In the context of healthy ageing, "ageing associated decline in intrinsic capacity", in very sharp contrast to the diagnosis of "old age", would be fully aligned with and reflect the ICD's purpose, and accomplish the ICD's envisioned resolutions. With global ageing, an urgent imperative exists to accurately assess population health and to holistically target maintenance and optimisation of physical and cognitive function, which would also be possible by enhancing ICD's reporting system with use of the term "ageing associated decline in intrinsic capacity". We believe there would be a substantial shift of focus with use of this term, from a static to a dynamic assessment of the person's health and capacity across a life trajectory.

Advanced pathological ageing should be represented in the ICD

The latest version of the International Classification of Diseases, ICD11, supports installed new dynamics in the nascent field of longevity medicine by classifying ageing as a disease. It allows physicians to target ageing in a comprehensive rather than a less efficacious disease and syndromes-oriented manner. Researchers have called for excluding old age from ICD-11, suggesting replacement by frailty.

Whether the term old age is the best choice of terminology for a state of multi-malfunction is a semantic, redundant debate. First, ICD codes are carefully considered and revised before being implemented. Secondly, frailty refers to, mostly but not exclusively, age-related disabilities, although old age is not always associated with frailty. Thus, these terms are not mutually exclusive and can co-exist in the ICD, as a part of a hierarchy of causation. The extension code XT9T guarantees coding for measurable age-related processes - eg, inflammageing, mitochondrial dysfunctions, etc.

The MG2A code, on the other hand, is representative of the paradigm shift in the definition of an individual's age, from chronological to biological, and will promote the development of therapies to optimise biological age. This paradigm shift in the definition of age, along with technological advances in the ability to control biological age, has led to considerable investment in the field of longevity to develop interventions targeting ageing mechanisms and systemic rejuvenation rather than a single organ or system at a time.


⫸ From a biological perspective, aging is a natural, multi-factorial phenomenon characterized by the accumulation of degradation processes, which in turn are supported by multiple changes and damages within molecular pathways (1). Such changes and damages will eventually impair the functions of cells and tissues. Therefore, aging is the most serious risk factor for almost all noncommunicable diseases, including cardiovascular diseases, tumors, diabetes and neurological diseases. ⫷ [2021 Common genetic associations between age-related disease

⫸ It is clear that with time the combination of many age-related processes becomes more granular and crystallizes into specific diseases. However, it is unclear when aging starts and when the transition between aging and pathology occurs.
⫷ 2015 Classifying aging as a disease in the context of ICD-11

You can view this as a tree like structure with the molecular and cellular age progression processes representing the trunk and limbs, and diseases as the small branches and leaves. The roots of this analogy are the development/growth/maturation protocol of a pre-pubescent youth. As the youthful signals diminish and aging signals increase within these networks, the disease-causing subsets are now primed by a new signaling cascade that enables/drive noncommunicable diseases. Image of this process can be found here: So, subsets of age defining networks are creating or facilitating the molecular environment that enable diseases, but as subsets, the emerging disease states are also directly communicating/indicating an advancing biological age state. A new treatment paradigm will emerge from this insight. Targeting the aging pathways that a specific disease occurs within, is likely to be one of the most effective disease ameliorating interventions available to practitioners in the near future. The most effective disease preventative intervention will ultimately be just targeting aging in and of itself.

Aging, diminishes functionality, increasing morbidity, leading to diseases, ultimately resulting in death. Thus: Aging is not a disease; Aging is the disease!

The ICD-11 should incorporate this reality.

Posted by: Michael Slattery at October 9th, 2022 8:26 PM
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