Is Sirt1 a miracle bullet for longevity?

The Sir2 (silent information regulator 2) family of nicotinamide adenine dinucleotide-dependent deacetylases has been implicated in the regulation of aging and longevity across a wide variety of organisms. Although controversial, Sir2 proteins have also been implicated as key mediators for the beneficial effects of caloric restriction (CR) on aging and longevity. In this issue, Bordone et al. report that transgenic mice in which the mammalian Sir2 ortholog Sirt1 is overexpressed mimic the physiological changes in response to CR. These findings have important implications for the development of CR mimetics and perhaps also for lifespan extension.