KLF control of aging and age-associated cardiovascular disease

(7)项目摘要/摘要 高龄是心血管疾病的主要独立危险因素。特定疾病的流行率 心血管疾病，如心脏肥大/衰竭、动脉粥样硬化和炎症，随着 年龄。申请人实验室以前的研究阐明了KLF在免疫控制中的重要作用， 代谢，以及对心血管系统的影响。申请人的初步意见建立在 已发表的工作语料库，并将KLF确定为迄今未被认识的分子控制点 管理寿命和健康跨越后生动物的生命。当前申请寻求(A)确定 哪些哺乳动物的KLF与衰老有关，(B)确定操纵KLF4对心脏和心脏的影响 和(C)确定操纵髓系KLF2对 衰老/年龄相关的炎症状态。完成概述的工作将提供基本的见解 对衰老和与年龄相关的心血管疾病具有治疗意义。

(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.