Fight Aging!

There is an ongoing debate in the research community over whether aging should be considered a disease, formally or colloquially. It has been running for a few years, but has picked up steam of late, and more of the discussion is in the form of open access papers these days. To pick a few examples from earlier this year you might take a look at a paper by David Gems or the thoughts of other European researchers associated with Heales. Here I'll point out a recent addition to the discussion in which the author opens with this summary:

The aging of the population represents one of the largest healthcare challenges facing the world today. The available scientific evidence shows that interventions are available now that can target fundamental "aging" processes or pathways. Sufficient economic evidence is available to argue convincingly that this approach will also save enormous sums of money which could then be deployed to solve other urgent global problems. However, as yet this scenario has barely entered the public consciousness and, far from being a point of vigorous debate, seems to be ignored by policy makers.

Understanding why this lethargy exists is important given the urgent need to deal with the challenge represented by population aging. In this paper I hypothesize that one major cause of inaction is a widely held, but flawed, conceptual framework concerning the relationship between aging and disease that categorizes the former as "natural" and the latter as "abnormal." This perspective is sufficient in itself to act as a disincentive to intervention by rendering those who hold it prone to the "naturalistic fallacy" but can give rise to active hostility to biogerontology if coupled with loose and/or blurred understanding of the goals and potential of the field.

One of the biggest puzzles of our time is why, given the obvious potential for biomedical research to treat the causes and progression of the aging process, is next to no-one interested in making this happen? We live in a culture in which it is taken for granted that treating cancer, heart disease, and Alzheimer's is the right thing to do. All of these are conditions caused by aging: they are not magically separate from the aging process. They arise from the same underlying forms of cell and tissue damage that cause all of the other manifestations of disability and frailty. Yet when asked about developing treatments for the underlying causes of aging, treatments that can be made more effective as therapies for age-related diseases than the present state of the art, there is a lack of interest and even outright hostility. Further, it isn't too hard to see that the same people who reflexively oppose the treatment of aging today would accept and use these treatments without question had they merely been born fifty years or a century from now. The whole situation seems very irrational.

I have been following this research and advocating for faster progress towards rejuvenation therapies like those of the SENS research programs for going on fifteen years now. Yet I still couldn't give you a good answer as to why the populations of the world are happy to walk towards a slow, crumbling suicide rather than support progress in medicine for aging. We all have our theories as to why things are the way they are, and no way to prove them: it is still too early on the path towards popular acceptance and support to draw any conclusions from the success of one message over another. The people in our community, who are choosing to make charitable donations to SENS and other research programs, are those who have had the big realization and have a better than average understanding of the research situation. We're not at the stage yet where SENS and other branches of aging research enjoy the support of a large fraction of the population in the same fashion as cancer research, donations given primarily for cultural rather than intellectual reasons.

Here are thoughts on the matter, some of which you might agree with, some of which you might not. As I said, everyone has their theories. Regardless of those, the small history lesson on changing views of aging and disease in the middle of this paper is interesting in and of itself:

Should we treat aging as a disease? The consequences and dangers of miscategorisation

The accusation that early gerontologists deliberately invented the distinction between ageing and disease because "by ring fencing their area of work intellectually, gerontologists hoped to ring-fence it financially" is unfounded and unfair. These early researchers were not making some cynical bid for a separate pot of grant money. Instead, they were echoing a medical tradition about the relationship between ageing and disease which predated not just the scientific method, but the English language.

Perhaps unfortunately for all concerned, this conceptual distinction between "natural" (and normal) aging and "unnatural" disease is ripe with the potential for fundamental philosophical error and "moral concern." At the inception of the field this was of limited importance because the potential for clinical intervention in later life problems was very limited. However, this has changed. In retrospect, the publication of Normal Human Aging in 1984 occurred at a gerontological watershed. The mid 1980s could be said to be a period in which something was known about why aging occurred, much was known about what changed as humans aged, but almost nothing about how this happened.

It is now clear that the finite capacity to replace lost cells plays a causal role in mammalian aging. Senescence is the permanent entry of individual cells into a viable, but non-dividing state, usually as the result of repeated cell division. The molecular pathways which trigger this process are complex but are now relatively well understood. Most recently it has been shown that interdiction of key nodes of the pro-survival gene expression networks upregulated in senescence (either pharmacologically or using siRNA) killed senescent cells, but not their proliferating or quiescent, counterparts. In vivo this resulted in extended healthspan. Since the production costs of these first generation "senolytics" are low such treatments are likely to be cost-effective.

Crucially, the same mechanisms of cellular senescence cause both age-related diseases, and features of aging considered in the past to be "natural changes" (e.g., the accumulation of senescent cells in the skin contributes to wrinkling, a "natural change" and to cardiovascular disease, an "age-related disease"). If the distinction between aging and age-related disease is false then the practical consequences of maintaining that such a distinction exists could be severe.

The proposition that aging and disease are distinct is easy to grasp, coherent and compelling. But it is important to recognize that it is essentially just an exercise in logic resting upon the definition of "disease" as abnormal function. Thinking about aging and disease like this raises surprising conceptual barriers to intervention. To illustrate this, imagine a land (let us call it "Nofruit") where everyone has scurvy. Following this logic, in Nofruit scurvy is considered by the population to be a "natural condition". Thinking like this is, in itself, a disincentive to research. In Nofruit the line of thinking would go: Diseases have "magic bullets" or cures. Most authorities think scurvy is not a disease so it cannot, by definition, have a cure. Thus, most Nofruit scientists wouldn't even try to find a cure for scurvy even though orange juice represents about as cheap and effective a "magic bullet" as can be imagined. The "problem" of scurvy would be tacitly ignored, much the way the possibility of successful intervention in aging is tacitly ignored in the real world.

It is important to recognize that the Nofruit arguments do not require aging and age-related disease to share causal mechanisms. Both may cause harm in different ways. However, in actuality the mechanisms which cause aging and age-related disease really do overlap very substantially. Thus distinguishing between "aging" and "age-related disease" probably represents an artificial distinction; human understanding has drawn an arbitrary line on the complex phenotype which is later life. Maintaining an artificial aging-disease distinction give rise to a contradiction. What is the ethical rationale for treating entities classified as "diseases" caused by senescent cells (like cardiovascular disease) but not treating entities classified as "natural changes" (like wrinkles) which are also caused by senescent cells? As yet this problem does not seem to have been fully recognized by bioethicists, probably because the science on which it is based is so new that it has not yet been disseminated. The little which has been said on the topic however, offers gerontologists little reassurance that our work will be well received.

However, research into public attitudes to gerontological research in the UK indicated a desire among the participants for a long and active life rather than to serve as object lessons in deliverance from suffering. It has been suggested that the concerns shown about extended lifespans by some participants in the Pew Research survey may result from their belief that these would be associated with the kind of morbidity seen in aging Americans today. If so this reinforces the key message that healthspan is the outcome most desired by our populations. The most effective way to facilitate this would be to significantly increase the funding available for research into the fundamental biology of aging and facilitate the rapid translation of its discoveries into the clinical arena.