Abstract
Conventional wisdom teaches that calorie restriction acts to increase longevity by reducing the metabolic rate and lowering the levels of reactive oxygen species that cause macromolecular damage. In a novel twist Lin et al. 1. Lin S-J. et al. Requirement of NAD and Sir2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science. 2000; 289: 2126-2128 Crossref PubMed Scopus (1477) Google Scholar link calorie restriction to the SIR locus in yeast, which mediates genomic silencing at telomeres, and propose a molecular mechanism by which this regimen causes increased longevity. Silencing at telomeres by Sir2p determines life span by triggering the deacetylation of specific lysines at the N terminus of histones, resulting in silenced chromatin. Sir2p has been shown to display NAD+-dependent histone deacetylase activity, thus creating a potential link between metabolism and ageing.
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