Role of Longevity Regulatory Pathways in Age-dependent Macro-molecular Damage in

描述（由申请人提供）：长寿调节途径在酵母中的β-依赖性大分子损伤中的作用在简单模式生物中调节寿命的基因和途径的鉴定对于初步理解哺乳动物衰老机制是非常宝贵的。本申请中提出的系统生物学和遗传学研究将有助于确定各种信号转导基因和途径在细胞凋亡中的作用。 单细胞真核生物S.啤酒。这些途径以Ras和Sch 9蛋白为中心，这些蛋白从酵母到人类都是保守的，并与癌症和其他疾病有关。拟议的研究将：1）阐明了负责先前鉴定的促衰老基因（包括RAS 2和SCH 9）的作用的基本分子机制，2）研究影响衰老和对损伤的抗性并且可能从酵母到人类保守的新分子、基因和途径，3）开发研究衰老的新范例，其更简单且更直接地与哺乳动物的衰老相关，4）研究热量限制的抗衰老分子机制，这些机制似乎从酵母到哺乳动物都是保守的。拟议的研究将有助于描述衰老的基本机制，并有助于识别可以预防人类疾病的新基因和途径。

DESCRIPTION (provided by applicant): Role of Longevity Regulatory Pathways in Age-dependent Macro-molecular Damage in Yeast The identification of the genes and pathways that regulate the life span in simple model organisms has been invaluable to the initial understanding of the mechanisms of aging in mammals. The systems biology and genetics studies proposed in this application will help define the role of various signal transduction genes and pathways in the regulation of aging and resistance to the damage caused by various stresses in the unicellular eukaryote S. cerevisiae. These pathways are centered around the Ras and Sch9 proteins, which are conserved from yeast to humans, and are implicated in cancer and other diseases. The proposed studies will: 1) shed light on the fundamental molecular mechanisms responsible for the effects of previously identified pro-aging genes including RAS2 and SCH9, 2) investigate novel molecules, genes, and pathways that affect aging and resistance to damage and that may be conserved from yeast to humans, 3) develop a novel paradigm to study aging, that is simpler and more directly relevant to aging in mammals, 4) investigate the anti-aging molecular mechanisms of calorie restriction, which appear to be conserved from yeast to mammals. The proposed studies will contribute to the description of the fundamental mechanisms of aging and also to the identification of novel genes and pathways that can protect against human diseases.