KLF control of aging and age-associated cardiovascular disease

KLF 控制衰老和与年龄相关的心血管疾病

• 批准号: 10335213
• 负责人: MUKESH Kumar JAIN
• 金额: $ 95.1万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10335213
• 关键词: Age; Aging; Atherosclerosis; Blood Vessels; Caenorhabditis elegans; Cardiac; Cardiovascular Diseases; Cardiovascular system; Control Locus; Elderly; Failure; Family; Guidelines; Heart Hypertrophy; Immunity; Inflammation; Inflammatory; Laboratories; Life; Link; Longevity; Mammals; Metabolism; Molecular; Myelogenous; Prevalence; Publishing; Role; Therapeutic; Work; cardiovascular risk factor; healthspan; insight

(7) Project Summary / Abstract Advancing age is a major independent risk factor for cardiovascular disease. The prevalence of specific cardiovascular conditions such as cardiac hypertrophy/failure, atherosclerosis, and inflammation increase with age. Previous studies by the applicant's laboratory illuminated essential roles for KLFs in control of immunity, metabolism, and impact on the cardiovascular system. Nascent observations by the applicant build on the published corpus of work and identify KLFs as a heretofore unappreciated molecular control locus governing both lifespan and healthspan across metazoan life. The current application seeks to (a) determine which mammalian KLFs are linked to aging, (b) determine the effect of manipulating KLF4 on cardiac and vascular healthspan in aging mammals, and (c) determine the effect of manipulating myeloid KLF2 on aging/age-associated inflammatory states. Completion of the outlined work will provide fundamental insights with therapeutic implications regarding aging and age-associated cardiovascular disease.

(7) 项目概要/摘要 年龄增长是心血管疾病的主要独立危险因素。具体的患病率 心血管疾病，如心脏肥大/衰竭、动脉粥样硬化和炎症会随着年龄的增长而增加 年龄。申请人实验室之前的研究阐明了 KLF 在控制免疫方面的重要作用， 代谢，以及对心血管系统的影响。申请人的新观察建立在 已发表的工作集并将 KLF 确定为迄今为止未被重视的分子控制位点 控制后生动物的寿命和健康寿命。当前的申请旨在 (a) 确定 哪些哺乳动物 KLF 与衰老相关，(b) 确定操纵 KLF4 对心脏和衰老的影响 衰老哺乳动物的血管健康寿命，以及 (c) 确定操纵骨髓 KLF2 对血管健康的影响 衰老/与年龄相关的炎症状态。完成概述的工作将提供基本见解 对衰老和与年龄相关的心血管疾病具有治疗意义。