A Summary View of Everything in Modern Longevity Science Except the Work that Really Matters

There are three classes of aging research, in order of decreasing size and funding: firstly the work that only investigates and catalogs aging, with no attempt to intervene; secondly work on ways to slow aging through metabolic and genetic alteration, which is doomed to very expensive and very slow progress to a marginal end result; and lastly work on repairing the cellular and molecular damage that causes aging. The latter is the only practical path forward to greatly extending healthy life and defeating age-related disease soon enough to matter for those of use reading this today. After a decade of advocacy to get to the present point of the existence of multiple labs and organizations such as the SENS Research Foundation explicitly funding work on rejuvenation biotechnology, if it has 1% of the funding of work on slowing aging, I'd be surprised. Work on slowing aging might in turn have 1% of the funding directed to merely studying aging. It is a frustrating situation, and must change.

The mainstream of modern research is steered by regulation into the inefficient process of examining late-stage mechanisms in disease and then working backwards. Since commercial development is only permitted to treat named diseases, and since putting potential treatments through the regulatory process generally requires demonstration of a comprehensive understanding of the relevant underlying biological mechanisms, the whole pipeline all the way back to funding for fundamental research is geared towards producing marginal impact on late stage disease in the most difficult way possible. Researchers struggle to understand the very complicated final stages of the disease process, with all its attendant confusion and interacting mechanisms of degeneration, and pull out some way to try to make our biological machinery work better while horribly damaged.

This is of course far from the best way to proceed for any machine, biological or not. The best way is to start with the much simpler roots of dysfunction, the damage that accumulates initially as a consequence of the ordinary operations of biological machinery, and block it before it spirals out into all sorts of different forms of dysfunction. Researchers know what that damage is - a list exists, well supported by evidence - and most of the arguments over how important it is and how exactly it connects to age-related disease could be settled by simply repairing that damage and observing the consequences. Working forwards in this way is a much, much cheaper prospect than trying to work backwards in the way forced by present regulation. Yet of course it is not the mainstream.

In fact, the approach of repairing the damage that causes aging is so very much not the mainstream that summary reviews of the state of the field such as the one quoted below can omit it entirely, focusing only on ways to alter metabolism to maybe slow down aging just a little bit. This is the real fight in the field of aging research now and for the next decade or two, the only important battle to my eyes: whether the research community (a) keeps on spending vast sums to better understand the fine details of how aging progresses while at the same time failing to do much of anything to actually help people, or whether (b) more than the present small minority of researchers wake up and turn to the better course of repairing damage, the course that offers a real chance of defeating degenerative aging and preventing the suffering and illness of old age.

Thus this review is not really a review of aging research; it is a review of work on slowing aging only, which is not all but rather only near all of the work presently aimed at intervening in the aging process. It is my believe that slowing aging is ultimately destined to be a dead end, producing only knowledge and no treatments of real value: it is most likely so very much harder and less productive than the repair approach that it will be displaced, but the repair approach is so much earlier in its development and funded to a fraction of the same level that it is taking time for this to become self-evident. So this is a review written from the position that repair of the causes of aging is not an option and that all we can really do is alter metabolism to slow the onset of damage. This is simply not the case, but those who hold to that position are right to assume that, by their metric and on their road, progress in the future will be hard, slow, and produce only marginal benefits.

Aging Research - Where Do We Stand and Where Are We Going?

The magnitude of the challenge is illustrated by considering known causes of aging. The good news is that many mechanisms causing aging, as well as pathways that can mitigate effects of aging, have been identified. This is also the bad news - aging processes and pathways offering an ability to modify their effects are extremely complex. It is widely assumed that aging is a major risk factor for most late-onset diseases (cancer, cardiovascular disease, diabetes, neurodegenerative diseases, etc.), and therefore interventions directed at aging offer an opportunity to ameliorate all these diseases at once. Although this idea has attracted much attention, we must also consider that the complexities of aging processes likely exceed those of specific diseases, and the challenge of reigning in the global decline of cellular processes across many tissues will be large.

We may have but scratched the surface of what bioinformatics can provide in identifying new genes and pathways important in human aging, as well as allowing for the knowledge we have already gained to be applied in a more effective, personalized way. Analysis of the transcriptome, epigenome, and proteome of individuals spanning a wide age range will provide the most detailed phenotyping of human aging so far.

If the genes and pathways that seem to correlate with slow or fast aging can be thus identified by big data analysis, resulting hypotheses about brain aging may be tested by conducting field studies. Possible treasure troves are the various long-term human longitudinal studies, which provide a cornucopia of health information spanning decades and, in some cases, provide access to genotyping. This may potentiate testing whether genetic haplotypes that correlate with slow or rapid aging identified bioinformatically exert predictable effects in a human population over the course of a lifetime. For example, one might test whether haplotypes correlating with slow molecular brain aging protect against cognitive decline or neurodegenerative diseases in these longitudinal studies.

The past two centuries have witnessed advances at many levels that allow people to live longer and more productive lives. I have attempted to place current research on the biology of aging into this context and have arrived at a few predictions. First, it will be more achievable and desirable to extend human health span rather than life span per se. Changes in maximum human life span will, in my opinion, be quite difficult to achieve and will take many years to even assess. From the point of view of economic and societal benefits, striving to make people healthier longer without necessarily extending their maximum life span may be the wisest course. Put another way, the nightmare scenario would be to extend maximum human life span without extending health span.

Second, bioinformatics will play a substantial role in the progress of aging research, especially as it applies to humans. There may already be buried in the sea of ever-increasing human genomic data novel clues about genes and pathways that govern aging in different tissues. In this regard, it remains to be seen how much of aging will prove to be systemic and affect all tissues simultaneously emanating from brain signals, for example, and how much will be tissue autonomous.

Third, aging and the genes and pathways that govern its effects are complex. It is not likely that there will be a silver bullet for aging any more than there will be a silver bullet for cancer. However, there will likely be novel pharmaceutical interventions for the effects of aging emerging directly from aging research. These interventions may need to be tissue specific, taking into account the personalized way aging impacts an individual tissue-by-tissue. Overall, it is an exciting, albeit uncertain, time to speculate how human health will be impacted in the decades to come by research on the biology of aging.


You rightly point out that pathetically small amounts of money are being invested in research into ageing and most of this does not go towards focused programmes aimed at discovering effective repair treatment, such as SENS.

An important contributory factor to this deplorable state of affairs is that governments spend much more of our money on miltary R&D than health research. I have started an epetition (see my URL) which, if it receives 100,000 signatures, will prompt a debate in the Commons about this glaring imbalance of funding. I urge you to sign and spread the word about this petition - surely most citizens would agree that our tax money should be focused on civilian and not military research?

Posted by: Richard Wilson at November 5th, 2014 8:57 AM

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