酵母Sirtuins在细胞寿命中的作用

Sirtuins mediated lifespan regulation in Saccharomyces cerevisiae

摘要:

酿酒酵母（以下简略为酵母）作为寿命分析模型广泛应用于寿命研究领域。酵母寿命分析方法有两种，分别是复制型酵母寿命分析法和时序型酵母寿命分析法。目前，通过酵母寿命分析模型已识别出包括SIR2在内的多个寿命调节基因。SIR2是目前较好的被确立起来的寿命调节基因，具有NAD依赖型脱乙酰化酶的活性，从原核生物到真核生物都有良好的保守性。Sirtuins（Sir2蛋白家族的总称）在细胞内具有功能上的多样性，其中包括对于压力耐受的调节、基因转录的调节、代谢通路的调节以及寿命调节作用等。Sir2是Sirtuins家族最早发现的成员，其功能是参与异染色质结构域转录的沉默调节，同时还参与复制型酵母寿命的调节。已证明，SIR2的缺失会缩短酵母的寿命，基因表达的增高会延长寿命。Sir2的高等真核生物的同源蛋白也被证实参与衰老相关疾病的调节。本文中，我们将阐述Sir2以及Sir2的酵母同源蛋白Hst1-Hst4的功能，以及由它们调节的酵母寿命。

Abstract:

Saccharomyces cerevisiae is a commonly used aging model. Aging in yeast is assayed primarily by measuring replicative lifespan (RLS) or chronological lifespan (CLS). Several longevity factors have been identified through RLS and CLS studies, including Sirtuins (Sir2 protein family members). Sirtuins are well-known aging factors and a class of NAD dependent protein deacetylases that are evolutionarily conserved from prokaryotes to higher eukaryotes. Sirtuins exhibit multiple intracellular functions, including stress response, gene transcription, cellular metabolism, and longevity. The Sir2 protein is the founding sirtuin family member that functions in transcriptional silencing of heterochromatin domains and as a pro longevity factor for replicative lifespan. Deleting SIR2 shortens replicative lifespan, while increased gene dosage causes extension. Furthermore, Sir2 homologs in higher eukaryotes have been implicated in mediating age related diseases as well. In this review, we summarize the role of Sir2 and its yeast homologs, Hst1 through Hst4, in replicative aging and chronological aging.