SIRT1 and Human Longevity

Some interesting news has surfaced from researchers working on uncovering the mechanisms of life extension through calorie restriction. From the Gerontology Research Group list (and via the transhumantech group) we have this:

Flachsbart and colleagues are reporting in Experimental Gerontology the result of a study many of us have been hoping to see. They assayed SNPs of SIRT1 in 1573 long-lived individuals (LLI) and find there is no association between longevity and any tested SIRT1 polymorphism or haplogroup. This does not rule out the possibility that lifespan-extending biochemistry or regimens (such as calorie restriction) might be acting through a separate pathway/mechanism in humans, as in yeast (reported by Kaeberlein and colleagues), or through another one of the other six sirtuins in humans. Consistent with this hypothesis Rose and colleagues have reported a weak association between polymorphisms of SIRT3 and male but not female longevity. This is unexpected since SIRT1 is probably the closer functional homologue of yeast Sir2 and C. elegans Sir 2.1 (since it is active in the nucleus and SIRT3 is active in mitochondria), and evidence has been pointing to SIRT1 being a regulator of lifespan in rodents. SIRT6 and SIRT7 might be even closer functional homologues to Sir2 since they are similarly localized within the cell: in heterochromatin and nucleoli. Association studies are probably underway for these two. Stay tuned.

The devil is in the details, as usual. As scientists close in on what makes calorie restriction work in humans, we may see calorie restriction mimetic drugs or therapies capable of reproducing modestly beneficial effects on metabolism and life span. As always, it should be noted that these sorts of metabolic tinkering are not the pathway to radical life extension - even if they work out, they are just a stepping stone to more effective anti-aging therapies capable of reversing age-related cellular damage.

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