Arguing that Public Reluctance to Treat Aging as a Medical Condition is at Root a Categorization Problem

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.

Comments

It seems that some pharmaceutical companies are at least warming up to the idea of intervening in the aging process. Is there a difference between classifying aging as a treatable condition vs classifying it as a disease? I'm surprised the looming threat of future healthcare costs really aren't being factored into the equation here.

I asked Aubrey de Grey yesterday how he felt about gaining favor amongst people, and he said that the tide was turning, but not fast enough... Still, some progress is better than none I guess?

Posted by: Ham at August 5th, 2015 6:58 PM

Do senescent cells actually cause wrinkles? I jumped to my old professor's article on the NCBI website and found no reference for that assertion.

Posted by: Jim at August 5th, 2015 8:42 PM

I think Professor Faragher is twisting himself into some logical knots in this paper to avoid explicitly acknowledging that extending healthspan will almost certainly extend lifespan (and healthy lifespan at that).

He is of course correct in stating "De Grey is committing something of a logical fallacy. The existence of impressive scientific breakthroughs today does not pre-ordain impressive scientific breakthroughs tomorrow.". But even since his debate with AdG a few years back there have been such notable developments such as the CRISPR-Cas9 gene editing system, single cell genomic analysis, microfluidic sorting of cells etc.

How many more breakthroughs are needed for a significant part of the SENS agenda to be implemented? Senescent cell removal and obviation of some mitochondrial gene deletions have in vivo demonstrations, and the later is entering a stage 3 clinical trial later this year. Stem cell treatments and cancer have a long way to go and are well funded. I think with each passing year assertions that we are no in steam engine time ring a little more hollow.

It still would be nice to have RMR to end this hand wringing once and for all though.

Posted by: Jim at August 5th, 2015 9:10 PM

Jim, SENS doesn't need "impressive scientific breakthroughs tomorrow". Once LEV is reached, the needed rate of progress to maintain it will be slower and slower... I think Faragher didn't grasp the concept quite well.

Posted by: Antonio at August 6th, 2015 2:42 AM

To be fair Antonio wouldn't you need treatments for sale in clinics in all 7 of the SENS categories in order to begin experiencing the Journey towards LEV? Removing Senescent cells is fine, but if you are still dying of heart disease caused by intra cellular junk or extra cellular matrix cross links then it isn't much help at all.

Looking at the trouble experienced in something supposedly well understood like beta amyloid causing Alzhiemers, and the lack of any therapeutic effect of amyloid clearing antibodies is pretty sobering.

And how far off is something like whole body gene editing?

Posted by: Jim at August 6th, 2015 11:35 AM

When Aubrey did his AMA the other day, and he left this link. This was funded by SENS themselves. http://www.sciencedirect.com/science/article/pii/S0040162515001985

He admittedly said it had a pessimistic tone in the abstract to serve as a wake-up call. The article shows positives and negatives on longevity, but I think definitely shows more of the potential negative unknowns, which tend to be socially based. A fair amount of society would end up having to change (it already should be anyways), and this draws a bit of attention to that. Social change tends to be slow. I've been getting the feeling that technologically we'll be able to solve aging... but only if society lets it happen. I'm all for all options and avenues being explored by everyone and having a good idea of what things could potentially look like, though. Do you think people in power or even people on the fence could read something like this and be swayed to not pursue longevity science?

Posted by: Ham at August 6th, 2015 1:52 PM

@Jim:

"To be fair Antonio wouldn't you need treatments for sale in clinics in all 7 of the SENS categories in order to begin experiencing the Journey towards LEV?"

Yes, of course, what have this to do with the need of accelerated progress or lack thereof?

Regarding Alzheimer's, it has been known from some time now that, apart from abeta plaques, tau fibrils and cell loss are also implicated in the disease, so it should not be a surprise that addressing only plaque formation doesn't do much to improve mental functions or stop its worsening.

Posted by: Antonio at August 7th, 2015 3:26 AM

Public reluctance for anti-aging technologies emanates from fear of old age. The public would rather spend their money on looking younger (hair treatments, contact lenses, plastic surgery, and Viagra, etc) than live longer. Also, retirees fear outliving their retirement money. When I show people a picture of an old wrinkled man blowing out 100 candles on his 100th birthday cake I always get the same reaction: "I never want to live that long." MIT conducted a survey years ago and found the public preferred biodegradable plastic and a totally automated home over the invention of an anti-aging pill. Tell people they might live another 30 years and they imagine living in a debilitated state, drooling at the mouth and confined to a wheelchair. The problem is humanity is creeping along to those extra 30 years without quality of life to accompany quantity of life. The "Longevity Divident" proposed by S Jay Olshanky is to prolong healthy independent life another 7 years, thus sparing Medicare from financial collapse. That is far short of the eternal youth proposed by a few longevity seekers, but it is a start. The first anti-aging pill of sorts to be studied in humans will be metformin, the anti-diabetic drug. It will only produce modest results as preliminary studies already reveal. Met formic primarily works by elevating AMPK, an energy-sensing molecule. Natural molecules like resveratrol and quercetin activate AMPK 200-fold better than metformin. But modern medicine isn't going to give its blessing on any anti-aging pill till it figures out how to cut itself into the money pot. End result: neither the public nor the professions want to lead the way to the doorstep of planned longevity.

Posted by: Bill Sardi at August 9th, 2015 8:12 AM

Resveratrol, NAD+ and so on are downstream consequences of aging and the dysfunction occurring upstream. The research by people like Dr Sinclair is first rate, however we need to go further upstream to tackle the root at a suitable intervention point instead of messing about with this pathway and that pathway.

Key pathways upstream of the complexity are viable targets and work by the Conboys for example focus on such intervention points.

So called modern medicine will have no issues getting a piece of the money pot when regenerative therapies are demonstrated either. An example of that is Grisfols the Spanish big pharma company, they are working with TWC lab to create a "cocktail" of factors to rejuvenate based on the parabiosis work. So clearly there is some interest in the field and some of the modern medicine people are clearly considering the possibilities.

Posted by: Steve H at August 10th, 2015 2:30 AM

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