Mechanism Of SIRT3 Improve Mitophagy By Inhibiting P53 To Protective Aging Myocardial

BackgroundAs the world’s aging population aising, the heart disease have become the frist kind of Public health’s "killer".The heart is the core of life organ, the heart of aging quality is directly related to human health and longevity. The remodeling of cardiac and(or) cardiac dysfunction as the main performance of myocardial aging, at the same time accompanied by myocardial cells become small, source of muscle fiber sparse, organelles degenerate, and a series of diseases characterized by cell apoptosis, for the development of heart failure, and eventually led to the deaths of patients.For seek the way that treatment aging and age-related diseases is imminent.Autophagy is important way that cellular remove protein wiht aging and damaged organelles, it is very important to maintain cellular homeostasis; And mitochondrial autophagy is refers to the cells through the mechanism that autophagy process of selective removal of mitochondria and mitochondrial autophagy closely associated with a variety of heart disease.Mitochondria to acetylation enzyme SIRT3 is SIRT2 homology yeast protein acetylation, Knock Out SIRT3 or SIRT3 expression decreased, can affect the metabolism of related diseases of aging, such as heart disease, cancer, etc.SIRT3 is one of the of sirtuin family, is a kind of Mitochondrial NAD dependence to acetylation enzyme, enzyme activity has to acetyl groups, SIRT3 in muscle, liver, heart, and brown adipose tissue metabolism active organizations such as the high expression. Macromolecular SIRT3 exists in cytoplasm, nuclei and Mitochondria, small molecule SIRT3 exists only in Myocardial cells of Mitochondria. As the growth of the age, SIRT3 level gradually reduce in the Myocardial cell, adjust the level of SIRT3 has become a forward-looking strategy of anti-aging. The condition of aging, SIRT3 expression decline is closely related to Mitochondrial dysfunction, increase SIRT3 can improve or reduce a variety of age-related degenerative diseases.ObjectivesDefinitize how to SIRT3 regulation mitochondrial acetylated in myocardial cell;Confirmed that SIRT3 expression to reduce whether leads to aging myocardial mitochondrial autophagy dysfunction, mitochondrial biosynthesis ability decline; Definitize SIRT3 whether regulating cell mitochondria autophagy level by P53- Parkin, to protect myocardial protection. MethodsBy Aerobic interval training(AIT) mice Model was established, Breeding C57 BL / 6 mice 22 to 24 months, normal diet.AIT on the aged mice after 12 weeks, Detection aged adult C57 BL / 6 mice, C57 BL / 6 mice and aged C57 BL / 6 + AIT mice cardiomyocytes SIRT3 expression level respectively, myocardial mitochondria degree of acetylation.Western blot method to detect SIRT3, MnSOD, PGC-1α, p16, P53 and P62, Parkin, GRP75, NDUFA9 expression level.Detection MnSOD, immune coprecipitation PGC-1α acetylation level.Using glucosinolates barbituric acid method(associates) determination of mouse myocardial malondialdehyde(MDA) content;Using active oxygen detection kit organization reactive oxygen species(ROS) level.Transmission electron microscope in the two groups the quantity change of myocardial mitochondria into autophagy vacuole, myocardial mitochondria merged into autophagy vacuole found aging significantly reduce the number of prompt aging myocardial mitochondrial autophagy is reduced. Results 1, compared with control group, the myocardial cell aging SIRT3 expression level decreased, mitochondrial acetylation increased, mitochondrial damage is aggravating; 2, AIT improve myocardial SIRT3 expression level, mitochondria acetylation decreased, mitochondrial biosynthesis ability increase; 3, compared with the control group, confirmed that SIRT3 can adjust its combined with P53 acetylation level; 4, compared with the control group, confirmed that SIRT3 regulating the level of mitochondrial autophagy to myocardial protection by P53- Parkin. ConclusionThis study confirmed that SIRT3 in cells in the regulation of mitochondrial acetylation, biosynthesis of the metabolic process of mitochondria plays the important role.Myocardial cell SIRT3 regulating cell mitochondria autophagy level, myocardial protection by P53- Parkin.Raised SIRT3 expression level, is the effective means for improving the capability of the aging of myocardial mitochondrial autophagy, slowing aging myocardial damage, myocardial protection.