MOLECULAR MECHANISMS OF AGING IN SACCHAROMYCES CEREVISIA

酿酒酵母老化的分子机制

• 批准号: 6509497
• 负责人: ETHAN E FORD
• 金额: $ 4.62万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6509497
• 关键词: ADP ribosylation; SDS polyacrylamide gel electrophoresis; Saccharomyces cerevisiae; adenine phosphoribosyltransferase; aging; chromatin; enzyme activity; histones; laboratory mouse; microorganism culture; nucleic acid structure; phosphodiesterases; point mutation; regulatory gene

Modern advances in medicine have caused an increase in the average life span of individuals. However, in today's era of an aging population, the molecular mechanisms of the aging process remain poorly understood. The recent identification of genes in Saccharomyces cerevisiae, Caenorhabditis elegans, and humans that effect the rate at which these organisms age has opened the door to the molecular and genetic characterization of the aging process. This research proposal addresses the aging process in S. cerevisiae by genetic and biochemical approaches. Specifically, these studies will examine the role and mechanism by which the silent information regulator protein, Sir2p, regulates S. cerevisiae life span. The SIR2 gene is involved in a number of chromosomal processes. Recent findings have suggested that Sir2p contains ADP-ribosyltransferase activity. This proposal will address the function of the putative Sir2p ADP-ribosyltransferase domain with respect to chromosomal dynamics and the regulation of aging. Because Sir2-like proteins are conserved in higher eukaryotes, these studies should provide insights into the role of Sir2-like proteins in mammalian species and possibly the aging process in mammals as well.

现代医学的进步使人的平均寿命延长了。然而，在当今人口老龄化的时代，衰老过程的分子机制仍然知之甚少。最近在酿酒酵母菌、秀丽隐杆线虫和人类中发现的影响这些生物体衰老速度的基因，为衰老过程的分子和遗传表征打开了大门。本研究拟从遗传和生化两方面探讨酿酒酵母的衰老过程。具体来说，这些研究将研究沉默信息调节蛋白Sir2p调节酿酒酵母寿命的作用和机制。SIR2基因参与了许多染色体过程。最近的研究表明Sir2p具有adp -核糖基转移酶活性。该建议将解决假定的Sir2p adp核糖基转移酶结构域在染色体动力学和衰老调节方面的功能。由于sir2样蛋白在高等真核生物中是保守的，这些研究应该为sir2样蛋白在哺乳动物物种中的作用以及可能在哺乳动物的衰老过程中提供见解。