Sins of Sinclair
A scathing review of Lifespan: Why We Age and Why We Don’t Have To by Sinclair and LaPlante (2019).
While age reversal is an old grift, the latest version has reached new heights of feigned legitimacy and hype.
all vertebrate animal species have a distribution of natural lifespans that are limited by their gene sets… Long-lived species like humans also provide a substantial investment in caretaking of offspring… advantages conferred to youth by parents mean that genetic selections for parental health are extant in caretaking species. Such genetic selections for post-reproductive health are not extant in non-caretaking species… for animals that can mate multiple times, longevity is an emergent property of the ability to continue to do all the things required to reproduce and promote the success of offspring….Think of it this way: if foxes can reproduce at 6 months, what genetic selections are present for them to live for six years? The ones that live for 6 years might reasonably produce 6 times as many offspring as those who perish in a year but those who die in a year would still contribute to the gene pool so long as they are successful at reproducing. Indeed, experiments done in flies that were selected for the ability to reproduce late in life suggest that hundreds or thousands of genes, not single dominantly acting genes, are modified to allow every organ system to function better over time in the resulting long-lived flies… However, animals in the wild are under little to no direct genetic selection for longevity beyond that to produce reproductive success.
Do sirtuins extend lifespan in yeast, invertebrates and vertebrates? Has Sinclair discovered sirtuin activators? Based on 25 years of work by ac- ademic and industrial investigators, the clear answer to both questions is no… Resveratrol is the molecule found in red wine that Sinclair claims as a sirtuin activator. There is a global consensus that resveratrol disturbs the assay used to measure sirtuin activity and generates a false signal… The global interest in sirtuins and sirtuin activators was such that companies—most notably GSK—spent many billions of dollars trying to get a positive result and could not because the so-called sirtuin activators do not activate sirtuins and because sirtuins are not longevity genes. Lifespan therefore represents a pivot in which a person central to the failure of the largest longevity medicine program in pharmaceutical history turns to the general public to retell his story. In the retelling, sirtuins are longevity genes and sirtuin activators are real.
As the premise of the book is that we do not have to age, it is no surprise that the book includes Sinclair’s daily regimen, which includes 1 g of type 2 diabetes drug metformin in addition to aspirin, resveratrol and three vitamins. While Sinclair tells people these are not recommendations for others, he advertises the page number on social media in response to being asked what to take for longevity. Indeed, there is clear evidence from social media that there are huge numbers of followers that believe that Sinclair is providing them with an inside track to extend healthy aging. The regimen is potentially damaging for individuals without type 2 diabetes as there is strong evidence that metformin use blunts the beneficial effects of physical activity
In the accompanying Lifespan podcast, Sinclair makes innumerable non-evidence based statements about benefits of time-restricted eating, statements about age-reversal as evidenced only by changing biomarkers (Fahy et al., 2019), and even potential immortality by repeatable drug treatments…