运动可以保护心脏老化所致心力衰竭，但具体机制不清楚。我们发现微小RNA-222是介导运动诱导的生理性心肌肥大的关键微小RNA，结果发表于Cell Metabolism。进一步发现，增加微小RNA-222可防治心肌细胞老化，但它是否在运动防治心脏老化所致心力衰竭中起作用尚不清楚。本项目拟结合功能获得性（慢病毒表达载体、过表达小鼠）和功能缺失性实验（基因干扰慢病毒载体、敲除小鼠），在动物（自然老化和快速老化）和细胞水平（自然老化和药物诱导老化）明确微小RNA-222在运动防治心脏老化所致心力衰竭中的作用。然后基于已鉴定的靶基因P27、Hmbox-1、HIPK1和HIPK2，进行细胞和动物整体水平的挽救实验，揭示微小RNA-222介导运动防治心脏老化所致心力衰竭作用的分子基础。本项目将明确微小RNA-222在运动防治心脏老化所致心力衰竭中的作用及分子基础，为心脏老化所致心力衰竭的治疗提供新靶点。

Cardiac aging leads to heart failure while exercise training can prevent aging-induced heart failure. However, the molecular mechanism underlying the beneficial effects of exercise training in aging-induced heart failure is unclear. .With the grant support from National Natural Science Foundation of China (81200169), we found that miR-222 was responsible for exercise induced physiological hypertrophy and this finding had been accepted by Cell Metabolism. Our preliminary data also indicated that miR-222 was decreased by doxorubicin induced cardiomyocyte aging while overexpression of miR-222 could attenuate that. .Based on these findings, we will firstly identify the role of miR-222 in the beneficial effects of exercise training in aging-induced heart failure by both in vivo and in vitro loss-of-function and gain-of-function experiments. Normal aging and accelerated aging models will be used in vivo with transgenic mice and knockout mice. Normal aging and drug-induced aging models will be used in vitro with miR-222-overexpressing lentivirus and miR-222 RNA interference lentivirus. Secondly, based on the identified target genes including P27, Hmbox-1, HIPK1 and HIPK2, we will perform the rescue experiments in vitro and then in vivo to identify the downstream target of miR-222 that mediates its protective effects in aging-induced heart failure. .Our project will prove that miR-222 contributes to the protective role of exercise training in aging-induced heart failure and provide novel therapeutic targets for aging-induced heart failure.