衰老为心力衰竭等老年人慢性疾病的主要危险因素，与Apelin异常有关。新近发现的Elabela可结合并激活Apelin受体APJ，参与心力衰竭的发病。前期研究中我们证实在老年心衰小鼠心脏组织中Apelin表达下调(Hypertension 2017)，但其作用不明。在此基础上，利用Apelin基因敲除(KO)、早衰老模型ku80KO小鼠及经TAC术诱导老年心衰损伤模型，通过Elabela、Apelin-13、APJ siRNA及重组SIRT6进行体内外干预实验，旨在探讨Elabela/Apelin-APJ轴对心肌氧自由基生成、DNA损伤修复因子、端粒耗损、衰老相关微小RNA(miR-122、miR-34a)、SA-b-gal及靶信号(AMPK-mTOR-FoxO3a、SIRT6-ku80)的影响，为确立Elabela/Apelin-APJ轴作为心脏等器官衰老及心衰损伤早期防治新靶点提供科学依据。

Aging is a major risk factor of chronic cardiovascular diseases including heart failure in aged people, which is a major public health problem in our country and relates to abmormality of Apelin. Recently, Elabela was identified as a new cardiovascular peptide that activate apelin receptor APJ and implicated in the pathogenesis of heart failure. Our previous study demonstrated that the levels of Apelin is reduced in hearts of aged mice with heart failure (Hypertension 2017), but its roles are still unknown. Based on this, the Apelin or ku80 gene knockout (KO) mice, aged mice with heart failure are used to induce cardiac injury animal models by pressure overload using aortic banding operation (TAC) or by an osmotic minipump with Ang II. In addition, Elabela, Apelin-13, APJ siRNA, and recombinant human SIRT6 are used for in vivo & in vitro intervention experiments on the above-mentioned animal model and cardiomyocytes in order to investigate the regulatory roles and relevant mechanisms of the Elabela-Apelin-APJ axis on oxidative stress, DNA damage and repaire factor, telomere consumption, aging-related microRNAs (miR-122, miR-34a), SA-beta-gal and target signaling (AMPK-mTOR-FoxO3alpha, SIRT6-KU80). Therefore, it has a prospective future and far-reaching significance on the aspects of basic study and clinical practice to to reduce the occurrence of cardiovascular events in patients with heart failure and to provide a scientific basis of the establishing the Elabela-Apelin-APJ axis as new targets for the early prevention of the cardiac senescence, dysfunction and damage.