How does metabolic rate affect age-induced genomic instability?

代谢率如何影响年龄引起的基因组不稳定性？

• 批准号: 7422081
• 负责人: WAYNE A VAN VOORHIES
• 金额: $ 8.26万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7422081
• 关键词: Address; Affect; Age; Age of Onset; Animal Model; Behavior; Biochemical Genetics; Biological; Carbon; Cell Aging; Cell division; Cell physiology; Cells; Complex; Dissection; Eukaryotic Cell; Event; Foundations; Genetic; Genome; Genomic Instability; Human; Incidence; Knowledge; Lead; Loss of Heterozygosity; Malignant Neoplasms; Measurement; Measures; Metabolic; Methodology; Methods; Mitochondria; Modeling; Mothers; Mutation; Nuclear; Numbers; Personal Satisfaction; Physiological; Process; Rate; Saccharomyces cerevisiae; Saccharomycetales; Source; Stem cells; Testing; Time; Yeasts; adult stem cell; age related; base; cell age; day; experience; human study; insight; interest; life history; mitochondrial dysfunction; mutant; prevent; trait; tumorigenesis

There are a myriad of hypothesis to explain the increased incidence of cancer with age. One of the major hypotheses suggests that high metabolic rate leads to increased cellular damage, including events that ultimately lead to cancer. The Gottschling lab discovered that as yeast cells age, they switch to a higher rate of genomic instability. We propose to use new methods developed in the Gottschling lab, to isolate old yeast mother cells, which are analogous to stem cells in metazoans and measure their metabolic rate - using methods developed in the Van Voorhies lab. We will combine this analysis with genetic and physiological alterations to determine whether metabolic rate impacts age-induced genomic instability in old mother yeast cells. This study will address fundamental issues in eukaryotic cells that may explain age-dependent oncogenesis.

有无数的假设可以解释癌症发病率随着年龄的增长而增加。其中一个主要假设认为，高代谢率会导致细胞损伤增加，包括最终导致癌症的事件。Gottschling实验室发现，随着酵母细胞的老化，它们的基因组不稳定性会更高。我们建议使用Gottschling实验室开发的新方法，分离旧的酵母母细胞，类似于后生动物的干细胞，并使用Van Voorhies实验室开发的方法测量它们的代谢率。我们将把这一分析与遗传和生理变化相结合，以确定代谢率是否影响衰老母酵母细胞中年龄诱导的基因组不稳定性。这项研究将解决真核细胞中可能解释年龄依赖性肿瘤发生的基本问题。