阿卡汀
粒体自噬
衰老
帕金
安普克
糖尿病性心肌病
品脱1
化学
细胞生物学
药理学
生物
生物化学
自噬
心肌病
内科学
医学
芹菜素
磷酸化
细胞凋亡
蛋白激酶A
心力衰竭
抗氧化剂
类黄酮
疾病
帕金森病
作者
Yi‐Xiang Hong,Wei‐Yin Wu,Fei Song,Chan Wu,Gui‐Rong Li,Yan Wang
出处
期刊:Aging
[Impact Journals, LLC]
日期:2021-06-27
卷期号:13 (12): 16381-16403
被引量:38
标识
DOI:10.18632/aging.203163
摘要
Cardiac senescence is associated with cardiomyopathy which is a degenerative disease in the aging process of the elderly. The present study investigates using multiple experimental approaches whether the natural flavone acacetin could attenuate myocardial senescence in C57/BL6 mice and H9C2 rat cardiac cells induced by D-galactose. We found that the impaired heart function in D-galactose-induced accelerated aging mice was improved by oral acacetin treatment in a dose-dependent manner. Acacetin significantly countered the increased serum advanced glycation end products, the myocardial telomere length shortening, the increased cellular senescence marker proteins p21 and p53, and the reduced mitophagy signaling proteins PINK1/Parkin and Sirt6 expression in aging mice. In H9C2 rat cardiac cells, acacetin alleviated cell senescence induced by D-galactose in a concentration-dependent manner. Acacetin decreased p21 and p53 expression, up-regulated PINK1/Parkin, LC3II/LC3I ratio, pLKB1, pAMPK and Sirt6, and reversed the depolarized mitochondrial membrane potential in aging cardiac cells. Mitophagy inhibition with 3-methyladenine or silencing Sirt6 abolished the protective effects of acacetin against cardiac senescence. Further analysis revealed that acacetin effect on Sirt6 was mediated by Sirt1 activation and increase of NAD+/NADH ratio. These results demonstrate that acacetin significantly inhibits in vivo and in vitro cardiac senescence induced by D-galactose via Sirt1-mediated activation of Sirt6/AMPK signaling pathway, thereby enhancing mitophagy and preserving mitochondrial function, which suggests that acacetin may be a drug candidate for treating cardiovascular disorders related to aging.
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