Resveratrol, lifespan, and an unhealthy diet

I heard this story at the Cold Spring Harbor Laboratory meeting on the Molecular Genetics of Aging about a month ago, and since then it’s been published online at Nature. The data were impressive at the conference and continue to be in the manuscript: Resveratrol extends life in mice, and appears to protect them from the health harms of a high-calorie diet. Baur et al.:

Resveratrol (3,5,4′-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

This paper is just the beginning, as the study is still underway: David Sinclair‘s group is also following cohorts of mice that are being fed either lab-standard or calorie-restricted diets, so we can expect another report in a few months’ time when those mice are expected to be expiring.

As of the CSHL conference, the CR and standard groups weren’t old enough to see any difference between their lifespans yet; consequently, there was no way to tell whether resveratrol was having a life-extending effect. The effect of resveratrol on the high-calorie animals was quite striking, however: their lifespan curves were essentially indistinguishable from the animals eating the less caloric diets.

Given that the high-calorie ad libitum diet is thought to be a good model of what we humans are doing to ourselves in the West, these results have convinced me to start investigating source of commercially available resveratrol. In the meantime, of course, I’ll continue drinking red wine…ad libitum.


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