Low-calorie diets extend lifespan in almost every model tested, but scientists can't yet agree on what controls this phenomenon. The histone deacetylase Sir2 provides a seductive link between gene silencing and calorie restriction (CR),1 but many debate the mechanism. Now researchers are turning to a new question: Does Sir2 have a role in CR-mediated longevity at all? While some still believe that Sir2 is the lynchpin of the CR-longevity pathway, others are more skeptical and propose alternative mechanisms. Recent findings haven't clarified the issue.
Some researchers, including biologist Leonard Guarente at Massachusetts Institute of Technology, contend that Sir2 is dependent on nicotinamide adenine di-nucleotide (NAD) and that CR activates Sir2 by reducing glucose metabolism, which increases the ratio of NAD to its reduced version, NADH.2 Others, such as Harvard Medical School pathologist David Sinclair, hold that nicotinamide, not NAD, is the control switch for Sir2, and that the deaminase Pnc1 ...
