Suppression of Phosphoinositide 3-Kinase Prevents Cardiac Aging in Mice
Suppression of Phosphoinositide 3-Kinase Prevents Cardiac Aging in Mice
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DOI：
10.1161/circulationaha.109.871137
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发表时间：
2009-10-27
期刊：
影响因子：
37.8
通讯作者：
Shioi, Tetsuo
中科院分区：
文献类型：
--
作者：
Inuzuka, Yasutaka;Okuda, Junji;Shioi, Tetsuo
背景心力衰竭是一种典型的年龄相关性疾病。虽然年龄相关的心脏变化可能易患老年人心力衰竭，鲜为人知的是心脏aging.Methods和结果的分子机制，我们分析了年龄相关的变化，在小鼠心脏和方式，其中抑制p110 α亚型的磷酸肌醇3-激酶活性修饰心脏衰老。老年小鼠的心脏功能下降与衰老标记物的表达有关。泛素化蛋白和脂褐素的积累，以及全面的基因表达谱，表明蛋白质质量控制的失调是心脏衰老的一个特征。抑制磷酸肌醇3-激酶可以保护心脏功能，并减弱与增强自噬相关的衰老标记物的表达。抑制的雷帕霉素，磷酸肌醇3-激酶的下游效应器的目标，也阻止了脂褐质积累在heart. Conclusions抑制磷酸肌醇3-激酶防止许多年龄相关的变化，在心脏和保存老年小鼠的心脏功能。（循环。2009;120：1695-1703.）
Background-Heart failure is a typical age-associated disease. Although age-related changes of heart are likely to predispose aged people to heart failure, little is known about the molecular mechanism of cardiac aging.Methods and Results-We analyzed age-associated changes in murine heart and the manner in which suppression of the p110 alpha isoform of phosphoinositide 3-kinase activity modified cardiac aging. Cardiac function declined in old mice associated with the expression of senescence markers. Accumulation of ubiquitinated protein and lipofuscin, as well as comprehensive gene expression profiling, indicated that dysregulation of protein quality control was a characteristic of cardiac aging. Inhibition of phosphoinositide 3-kinase preserved cardiac function and attenuated expression of the senescence markers associated with enhanced autophagy. Suppression of target of rapamycin, a downstream effector of phosphoinositide 3-kinase, also prevented lipofuscin accumulation in the heart.Conclusions-Suppression of phosphoinositide 3-kinase prevented many age-associated changes in the heart and preserved cardiac function of aged mice. (Circulation. 2009;120:1695-1703.)