KLF control of 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。具体的流行情况 心血管疾病，如心脏肥大/衰竭、动脉粥样硬化和炎症， 年龄申请人实验室的先前研究阐明了KLF在控制免疫中的重要作用， 代谢和对心血管系统的影响。申请人的初步观察是基于 发表的工作语料库，并确定KLF作为一个迄今为止不受重视的分子控制基因座 控制着后生动物的寿命和健康。本申请旨在（a）确定 哪些哺乳动物KLF与衰老有关，（B）确定操纵KLF 4对心脏的影响， （c）确定操纵髓样KLF 2对老年哺乳动物血管健康的影响， 衰老/与年龄相关的炎症状态。完成概述的工作将提供基本的见解 具有关于衰老和与年龄相关的心血管疾病的治疗意义。

(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.