MOLECULAR MECHANISMS OF AGING IN SACCHAROMYCES CEREVISIA

酿酒酵母老化的分子机制

• 批准号: 6447047
• 负责人: ETHAN E FORD
• 金额: $ 4.02万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6447047
• 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.

现代医学的进步导致了个体平均寿命的延长。 然而，在当今人口老龄化的时代，人们对​​衰老过程的分子机制仍然知之甚少。 最近在酿酒酵母、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。 该研究计划通过遗传和生化方法解决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 基因参与许多染色体过程。 最近的研究结果表明 Sir2p 含有 ADP-核糖基转移酶活性。该提案将解决假定的 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，因此这些研究应该可以深入了解 Sir2 样蛋白在哺乳动物物种中的作用以及可能的哺乳动物衰老过程。