心肌层纤维化增加和心脏干细胞数目与功能的下降是心脏衰老的重要表型。阐释上述衰老表型发生及干预的分子机理是阐明心脏衰老分子机理与延缓心脏衰老急需解决的难题。最新研究表明心脏衰老伴随心肌细胞自我更新功能下降。我们最近率先报道：存在于心肌层的间质细胞--心脏Telocytes（CTs）有减小梗死心肌面积及心肌纤维化的疗效；进一步研究证明：CTs能促进缺血边缘区心肌细胞增殖及通过其分泌的外泌体miRNAs促进心脏干细胞在缺氧环境的存活。这些研究提示：CTs衰老在心脏衰老的心肌细胞自我更新、心脏干细胞激活与存活下降及心肌层纤维化增加的发生充当重要调控功能。本项目将对CTs衰老分子机理，及CTs衰老对上述心脏衰老重要表型发生的分子机理进行研究，揭示心脏衰老新的分子机理，为延缓随增龄心肌细胞自我更新、心脏干细胞激活与存活下降、心肌层纤维化增加、及心脏再生能力下降等心脏衰老表型带来新的分子机理及干预方法。

Increase of Cardiac fibrosis and Decrease of number and function of cardiac stem cells are critical phenotypes of heart aging. Revealing of the molecular mechanism and the interventional strategy regarding to above aging phenotypes are crucial issue for us to demonstrate molecular mechanism of heart aging and delay heart aging. The up-to-date studies document that the renewal of cardiac myocyte is decreased during heart aging. Recently, we reported firstly that a novel interstitial cell, named as cardiac telocytes (CTs), is able to decrease infarct size and cardiac fibrosis in myocardial infarction (MI). Further studies also reveal that CTs are able to promote the proliferation of cardiac myocytes in border zone and survival of cardiac stem cells in hypoxia via miRNAs included in CTs secreted exosomes. The findings propose that CT aging might play an important role in deduction of renewal of cardiac myocytes and activation & survival of cardiac stem cells, and increase of cardiac fibrosis included in heart aging. The proposed project was therefore designed to investigate the molecular mechanism of CT aging, and its effects in above aging phenotypes in order to reveal novel molecular mechanism for heart aging. The results of present study will establish the novel molecular mechanism, targeting and interventional methodology for delay of dysfunction of cardiac myoctyes renewal, cardiac stem cell activation and survival, and improvement of cardiac fibrosis and regeneration of MI.