Genes Specifying Aging and Longevity in the Mouse

小鼠衰老和长寿的基因

• 批准号: 7253998
• 负责人: Thomas E. Johnson
• 金额: $ 30.41万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7253998
• 关键词: Aging; Blood Glucose; Body Temperature; Body Weight; Cause of Death; Condition; Data; Eating; Etiology; Exhibits; Female; Fertility; Genes; Genetic; Growth; Hair; Health Sciences; Heritability; Hormonal; Insulin; Insulin-Like Growth Factor I; Invertebrates; Life Expectancy; Life Extension; Longevity; Mammals; Maps; Measures; Metabolic; Methods; Mus; Pathology; Physiological; QTL Genes; Quantitative Trait Loci; Rate; Recombinant Inbred Strain; Recombinants; Reporting; Rodent; Signal Transduction; Specific qualifier value; Tail; Testing; Variant; anti aging; dietary restriction; end of life; genetic analysis; insulin sensitivity; response; trait

DESCRIPTION (provided by applicant): Dietary restriction (DR) is the most validated method of extending longevity and slowing aging in rodents. Multiple physiological responses are seen after imposition of DR and many of these have been put forth as potential causal factors in producing the life-extension benefits of DR. We have found that several of the physiological effects of DR have a substantial genetic component and are amenable to genetic analysis. Moreover, several of these traits are specified by distinct sets of genes. We propose to use this substantial body of preliminary results to establish a relationship within and among various traits that respond to DR and to establish the relationship between these traits and the longevity-extension that is the hallmark of DR. We propose to map the genes (QTLs) underlying these traits and determine whether DR-induced life extension is genetically associated with one or more of these responses, consistent with a causal relationship. Phrasing this as a hypothesis, we propose that there are identifiable QTLs that underlie variation in the physiological responses to DR and that some of these QTLs are associated with significant life extension in response to DR. Using the LSXSS RI panel, we have obtained preliminary data for several responses to DR, including lowered body temperature, reduced body weight, slower growth rate, and reduced female fertility during DR and extended female fertility after restoring ad lib (AL) conditions. Additional studies to further these findings are underway. Here we propose to identify and map QTLs specifying life span and end-of-life pathology under both AL and DR conditions. We also will assess levels of blood glucose, insulin, and IGF-1 and map QTLs for these traits. These QTLs will be mapped using the LXS RI strains, a new RI set and the largest set of RIs ever constructed (77 strains).

描述（由申请人提供）：饮食限制（DR）是延长寿命和减慢啮齿动物衰老的最有效的方法。强加了DR之后，可以看到多种生理反应，其中许多被认为是产生DR生命延长益处的潜在因果因素。我们发现，DR的几种生理作用具有实质性的遗传成分，并且可以接受遗传分析。此外，这些特征中的几个由不同的基因集指定。我们建议使用这种大量的初步结果，以建立对DR响应并建立这些特征与寿命扩展之间的关系的各种特征之间的关系，这是DR的标志。我们建议绘制这些特征的基因（QTL），并确定DR诱导的寿命延长是否与这些反应中的一个或多个有关，与因果关系一致。 将其作为一个假设，我们建议有可识别的QTL是对DR的生理反应差异的基础，并且其中一些QTL与DR的重大寿命相关。使用LSXSS RI面板，我们获得了对DR的多种反应的初步数据，包括体温降低，体重降低，生长速度降低以及在恢复AD LIB（AL）条件后DR和延长的女性生育过程中的女性生育能力降低。 进一步的其他研究正在进行中。在这里，我们建议在AL和DR条件下识别和绘制指定寿命和寿命终结病理的QTL。我们还将评估这些特征的血糖，胰岛素和IGF-1的水平，并MAP QTL。这些QTL将使用LXS RI菌株，新的RI组和有史以来最大的RIS构建（77个菌株）映射。