Restriction of calorie intake increases lifespan in many organisms, including mammals, and is mediated by gene silencing at telomere and rDNA loci through the activity of a nicotinamide adenine dinucleotide (NAD+) –dependent histone deactylase, Sir2. NAD is produced either de novo, or by recycling NAD degradation products in the salvage pathway, where nicotinamide is the starting point. It has been unclear if increasing NAD levels activate Sir2, or decreasing levels of nicotinamide relieve the inhibition of Sir2. In May 8 Nature, Rozalyn Anderson and colleagues at Harvard Medical School, Boston, further address the issue in yeast by focusing on the nicotinamide cleaving enzyme, PNC1 (Nature 423:181-185, May 8, 2003).

Anderson et al. used deletion mutants to demonstrate that PNC1 is necessary for the beneficial effects of calorie restriction (CR) and that additional copies of the gene dramatically increase lifespan. They created a PNC1 and...

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