More restrictions on sirtuins’ role in calorie restriction

Following up on yesterday’s post, more about genetic regulation of lifespan in our favorite single-celled eukaryote: Calorie restriction (CR) extends both replicative and chronological longevity in yeast, but the role of the longevity-assurance genes known as sirtuins is controversial — in other words, scholars in the field disagree whether sirtuins are required for the increase in life expectancy caused by CR, especially in yeast. This is important because it gets us into questions like, “Is resveratrol a calorie-restriction mimetic, or does it exert its life-extension benefits via some other mechanism?”

The controversy has generally revolved around replicative lifespan, but a recent paper addresses the other side of the issue: Smith et al. demonstrate that loss-of-function mutants in yeast SIR2 and its homologs are still able to live chronologically longer in response to CR. This is relevant to mammals at least to the extent that nutrient-limited, nondividing yeast (the state they’re in for measurements of chronological lifespan) are a good model for persistent non-dividing cells with a tissue (i.e., G0 or even senescent cells).