日本科学家成功地阻止了年龄化老鼠心脏相关的变化，他们通过抑制PI3K基因维持了心脏的功能。

这项研究结果发布在Circulation上，为“延缓或阻止人类心脏衰竭或许是可能的”这一结论，提供了证据。

过早老化是心脏衰竭的一个主要风险因子。其中一个原因就是老龄化使心脏暴露于心血管风险因子环境的机会增加。然而，由于老龄化导致的自然变化可能危及心血管系统。

研究人员观察了遗传学设计的老龄化老鼠，发现其抑制了一种叫PI3K基因的活性。PI3K是insulin/IGF-1信号系统的一部分，能够调控细胞的生命周期。PI3K的变异体，是p110α的同型体，对组织老龄化具有重要作用。

研究人员发现，抑制同型体的活性延缓了蛔线虫(roundworm C. elegans)的生命。在果蝇中，这种抑制则阻止了老龄化相关的心脏功能衰减。

研究人员比较了具有p110α活性和p110α活性抑制的老鼠，在活性抑制的老鼠中发现一下几点：

心脏功能增加；
纤维化减少；
老龄化生物学标记减少；
心脏基因的表达模式就像年轻的老鼠。
这项发现表明，通过修饰胰岛素的功能，心脏的老龄化能够被阻止，这为阻止老龄化相关的心脏衰竭铺设了道路。

原始出处：

Circulation. 2009 October 12, 2009, doi: 10.1161/CIRCULATIONAHA.109.871137

Suppression of Phosphoinositide 3-Kinase Prevents Cardiac Aging in Mice

Yasutaka Inuzuka MD, Junji Okuda MD, Tsuneaki Kawashima MD, Takao Kato MD, Shinichiro Niizuma MD, Yodo Tamaki MD, Yoshitaka Iwanaga MD, PhD, Yuki Yoshida MD, PhD, Rie Kosugi MD, PhD, Kayo Watanabe-Maeda MD, PhD, Yoji Machida MD, PhD, Shingo Tsuji PhD, Hiroyuki Aburatani MD, PhD, Tohru Izumi MD, PhD, Toru Kita MD, PhD, and Tetsuo Shioi MD, PhD*

From the Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Y. Inuzuka, J.O., T. Kawashima, T. Kato, S.N., Y.T., Y. Iwanaga, T. Kita, T.S.); Department of Cardioangiology, Kitasato University School of Medicine, Kanagawa (Y.Y., R.K., K.W.-M., Y.M., T.I.); and Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo (S.T., H.A.), Japan.

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 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.