"But So Does Aspirin"

Every so often along comes a new over-hyped drug candidate with studies showing it extends life in laboratory animals. People throw away common sense and buy the stuff for a few years until the hype wears off in the face of more scientific evidence that throws doubt upon the early claims, and the realization that, like all the preceding drug candidates, this latest one also does next to nothing to impact the progression of aging in humans.

It helps greatly to realize that life span and health are much more plastic in short-lived species than in comparatively long-lived species such as we humans. All sorts of things extend life in lower animals by a large amount yet have no such result in humans. Consider calorie restriction for example, which extends life by 40% in mice, but certainly doesn't do as much in humans. Did you know that ibuprofen use meaningfully extends life in a number of species to a an equal or greater level than metformin, a currently hyped drug candidate to slow aging? Or that aspirin has sizable effects on life span in short-lived species as well? Yet clearly neither of those extends human life span to anywhere near the same degree, despite decades of use and a great deal of data on its effects.

Chasing meaningful effects from drug candidates such as metformin is irrational based on what is known to date. It is not where the research community should be putting time and money. When people point to the effects in animal studies, noting that in some of these metformin is shown to extend life, you can say "but so does aspirin, and that certainly doesn't have the same effect on life span in people."

We examined the impacts of aspirin and metformin on the life history of the cricket Acheta domesticus (growth rate, maturation time, mature body size, survivorship, and maximal longevity). Both drugs significantly increased survivorship and maximal life span. Maximal longevity was 136 days for controls, 188 days (138% of controls) for metformin, and 194 days (143% of controls) for aspirin. Metformin and aspirin in combination extended longevity to a lesser degree (163 days, 120% of controls). Increases in general survivorship were even more pronounced, with low-dose aspirin yielding mean longevity 234% of controls (i.e., health span).

Metformin strongly reduced growth rates of both genders (less than 60% of controls), whereas aspirin only slightly reduced the growth rate of females and slightly increased that of males. Both drugs delayed maturation age relative to controls, but metformin had a much greater impact (more than 140 % of controls) than aspirin (~118 % of controls). Crickets maturing on low aspirin showed no evidence of a trade-off between maturation mass and life extension. Remarkably, by 100 days of age, aspirin-treated females were significantly larger than controls (largely reflecting egg complement). Unlike the reigning dietary restriction paradigm, low aspirin conformed to a paradigm of "eat more, live longer." In contrast, metformin-treated females were only ~67 % of the mass of controls.

Our results suggest that hormetic agents like metformin may derive significant trade-offs with life extension, whereas health and longevity benefits may be obtained with less cost by agents like aspirin that regulate geroprotective pathways.

Link: http://dx.doi.org/10.1007/s11357-015-9769-x


Don't throw the baby out with the bathwater!

If we want to see rejuvenation cures in medicine, first of all, aging must be considered as a condition that needs treatment. Metformin and Salicylic acid are good candidates that pave the way because they are already used to treat age related diseases.

The real breakthrough isn't the comparatively small lifespan effect of these two drugs, but rather their potential new indication for use!

Posted by: Prometheus at July 20th, 2015 8:12 AM

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