Making Sense of Senescence

Historical research we discussed previously proposed that significant increases in average life expectancy would require the cure of multiple diseases of aging. Without considering the detail of cause-of-death calculations conducted more than two decades ago, it certainly seems implausible even now that we'll cross such a dramatic Rubicon in the near-term. Of course, while complete cures grab headlines, any form of simultaneous progress against aging disease could still provide substantial improvements in healthy lifespan.

One way to target simultaneous progress against multiple diseases of aging would be to find plausible common factors to act against. Increasingly, researchers believe a plausible common factor is systemic inflammation, and work has implicated inflammation in the development of type 2 diabetes mellitus, neurodegenerative disease, atherosclerosis and cancer. Indeed, the inflammatory component of cancer is far from being a recent idea; it was first postulated by Rudolf Virchow more than 150 years ago.

If inflammation is a common factor in multiple diseases, then interventions that reduce inflammation should prove effective. Research suggests that this may be the case, although it isn't always easy to attribute causality where a therapy has a range of effects. Exercise has been found to be anti-inflammatory as well as protective against aging disease, and although the mechanisms of action have not been fully understood, the benefits have been repeatedly shown. Aspirin, in addition, is a drug with anti-inflammatory activity, and it appears to offer some benefit against vascular disease and certain types of cancer.

A significant component of chronic inflammation as we age appears to be the change in state of mature cells known as cellular senescence. It has been found that sensescent cells don't have a quiet retirement, but instead secrete a number of pro-inflammatory factors. There is now emerging evidence to show that one way exercise exerts its beneficial effect may actually lie in reducing this burden of cellular senescence.

To date, intervention trials have been in mouse models. When the removal of senenscent cells by gene therapy enhanced health-span in mice with progeria, this prompted researchers to consider the creation of senolytic treatments, drug interventions to remove senescent cells en masse. The most recent trials suggest an up-to 30% healthy lifespan extension for mice after the majority of their senescent cells were removed. This is a striking result, but despite our shared fondness for cheese, human biology is distinctive and complex; only a minority of therapies successfully cross the species barrier. Such caveats aside however, could the selective removal of senescent cells mitigate a broad swathe of aging disease? At least one commercial company seems to think so. If they prove correct, this single intervention has the potential to deliver significant social and economic benefit.


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Gavin Ritchie
Gavin Ritchie is the IT Director of Longevitas