The Great Sirtuin Debate

REFERENCE: Burnett et al. “Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila.” Nature (2011) 477, pgs 482 – 485.

                It all started with a report that overexpression of SIR2 in budding yeast led to increased lifespan.  Follow up studies showed similar results in C. elegans and Drosophila, which lead researchers to pursue the relationship between calorie restriction (a known way to extend lifespan) and sirtuin expression.  These results bore resveratrol, a purported activator of human Sirtuin 1 (SirT1), which most of the general public will tell you is a component of red wine.  

                The dissent on the role of resveratrol and sirtuins in lifespan extension comes from labs at the University of Washington, University of Wisconsin, Amgen Inc., and Pfizer, among others.  Their papers explicitly say resveratrol has no activating properties on SirT1, conclusions which they back up with control studies using the Fleur-de-Lys system and crystal structures.

                Another blow to the importance of sirtuins came in a recent issue of Nature.    Burnett et al. studied C. elegans and Drosophila overexpressing sir-2.1 and closely accounted for the genetic backgrounds of each.  When taking into account these parameters, longevity increase was no longer noted.  Within fruit flies, the authors further concluded that dietary restriction did increase fly lifespan but was not dependent on Drosophila Sir2.  

Gem and colleagues stress the importance of “…controlling for genetic backgrounds and for the mutagenic effects of transgene insertions in studies on genetic effects on lifespan.”  As for the importance of sirtuins, they cannot support a strong relationship between sirtuins and lifespan extension.