“I resolve to not get any older.”
This may seem like a somewhat outlandish New Year’s resolution, a desire more grounded in the realm of science fiction than science itself. But a growing group working in the field of biogerontology would argue that it is not. I was able to get an update on the state of the science at a session organized by Dr. Aubrey de Grey, Chief Scientific Officer of the anti-aging organization SENS (Strategic Engineering Negligible Senesence) Research Foundation, last month at the World Stem Cell Summit in San Diego.
The allure of slowing the clock of aging has long held a special place in human imagination, but has been considered to lay on the fringes of scientific reality by many, until recently. Dr. de Grey, an outspoken public advocate for life extension research who has delivered numerous TED talks and public lectures on the topic, published a controversial position piece in 2005 advocating for a more open dialogue on the topic. In response, EMBO Journal published a 28-author critique of SENS and its position on aging research alongside a rebuttal from Dr. de Grey. The articles took opposite sides on the legitimacy of the claims being forwarded by SENS, and were largely squared off on the grounding of such claims in plausible scientific progress.
In the eight years since, the field has done much to establish itself, well summarized by a review in Cell last year outlining the “nine hallmarks of aging” that have been targeted therapeutically in mice. Citing gains in cancer research since the foundational 2000 paper outlined the six causative molecular mechanisms in tumorogensis (later expanded to ten factors in a 2011 update), the review describes how the interconnectedness of these hallmarks may have masked potential gains in extending life. By dissecting the relative contribution of each factor, the goal of improving human health during aging via pharmaceutical means could be closer than we think.
Although it is generally accepted that lifestyle and diet modifications such as caloric restriction can lead to a slowing of age-related degeneration, controversy begins to emerge around evidence supporting therapeutic interventions such as sirtuins, rapamycin and resveratrol. At the Summit, panelist Dr. Brian Kennedy of the Buck Institute for Research on Aging, said that although there is as of yet no proof of pharmacological extension of human life, given the encouraging evidence in mice and growing understanding of underlying biological causes, it is very plausibly within our reach.
Dr. de Grey was careful to make an important distinction about this vein of research and addressed what is known as the “Tithonus Error” – an assumption that postponing aging would extend ill-health rather than health span. In the Greek legend, Tithonus was granted immortality by Zeus at the bequest of his Titan lover and kidnapper, Eos, who in an unfortunate twist forgot to ask for Tithonus’ eternal youth, cursing him to living forever in a “loathsome old age…unable to move nor lift his limbs”. This public misconception thus mistakes the goal of biogerontology to extend the unhealthy phase of our life rather than the healthy. The therapeutic goal is to shift the balance between how much of our lives are lived as healthy and productive members of society and delay or prevent the onset of age-related disorders such as cancer, cardiovascular disorders and neurodegenerative disease (to name a few). Dr. de Grey recently examined the state of messaging related to biogerontology and expounded upon the risks in promising too much in the field, lessons that have certainly been learnt in the field of stem cell research and gene therapy. It is clear from the highly accomplished scientific advisory board of SENS Research Foundation that there is considerable conceptual backing behind their goals, but a clear takeaway from the session was that they have only recently begun to enter the area of realistically achieving their goals and meeting expectations.
With Google recently announcing that it is getting into the biotechnology space through the backing of Calico, a new biotech company headed by former Genentech CEO Art Levinson that will focus on anti-aging therapeutics, it appears this line of research is very much headed for the mainstream. Although we should be cautious of the timeline of such therapies, the ability to therapeutically extend healthy human life may very well be realized within our lifetimes.
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