Sir2: An NAD-dependent Histone Deacetylase That Connects Chromatin Silencing, Metabolism, and Aging

作者：Shin‐ichiro Imai, F. Brad Johnson, Robert A. Marciniak, Mitch McVey, P.U. Park, L Guarente · 发表于：Cold Spring Harbor Symposia on Quantitative Biology · 年份：2000 · DOI：10.1101/sqb.2000.65.297 · 被引用次数：153 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、Sirtuins and Resveratrol in Medicine、Genomics, phytochemicals, and oxidative stress

Aging is a biological process that shows deleterious,progressive, intrinsic, and universal changes in an organism over time (Strehler 1982). These destructive changeseventually produce an exponential increase of mortalityrate (Gompertz 1825), which can be widely observed in avariety of organisms including the budding yeast Saccharomyces cerevisiae (Sinclair et al. 1998). Different typesof damage, especially oxidative damage, and variousforms of genomic instability have been suggested to beinvolved in the aging process (Johnson et al. 1999). In thecase of budding yeast, longevity is measured by the number of daughter cells that a mother cell can produce (Mortimer and Johnston 1959). The stability of ribosomalDNA (rDNA) repeats is crucial to determine thelongevity of the yeast mother cell (Sinclair and Guarente1997). The rDNA region consists of 100–200 tandemcopies of an approximately 9.0-kb rDNA unit and therefore presents a large target for homologous recombination. Playing a major part in the regulation of the frequency of recombination at this locus is the yeastsilencing protein Sir2 (Gottlieb and Esposito 1989),which is also a limiting component for longevity (Kaeberlein et al. 1999). Deletion of SIR2 shortens life span toabout one half of wild type, and an extra copy of SIR2 significantly extends life span. Sir2 is one of the principalregulators of transcriptional silencing in yeast, along withSir3 and Sir4 at telomeres and silent mating-type (HM)loci (Rine and Herskowitz...