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

描述(申请人提供)：寿命调节通路在酵母中依赖年龄的大分子损伤中的作用在简单的模式生物中识别调节寿命的基因和通路对于初步了解哺乳动物的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不同的信号转导基因和通路在 单细胞真核生物酿酒酵母衰老的调节和对各种胁迫损伤的抵抗。这些途径围绕着Ras和Sch9蛋白，它们从酵母到人类都是保守的，与癌症和其他疾病有关。拟议的研究将：1)阐明先前已确定的促衰老基因包括RAS2和SCH9的影响的基本分子机制；2)调查影响衰老和抗损伤并且从酵母到人类可能保守的新分子、基因和途径；3)开发一种新的范式来研究衰老，更简单和更直接地与哺乳动物的衰老相关；4)研究限制卡路里的抗衰老分子机制，似乎从酵母到哺乳动物都是如此保守。拟议的研究将有助于描述衰老的基本机制，也有助于识别可以预防人类疾病的新基因和新途径。

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.