Modulating effect of SIRT1 activation induced by resveratrol on Foxo1-associated apoptotic signalling in senescent heart.

摘要: Elevations of cardiomyocyte apoptosis and fibrotic deposition are major characteristics the ageing heart. Resveratrol, a polyphenol in grapes red wine, is known to improve insulin resistance increase mitochondrial biogenesis through SIRT1-PGC-1α signalling axis. Recent studies attempted relate SIRT1 activation by resveratrol regulation various disease models cardiac muscle. In present study, we tested hypothesis that long-term (8-month) treatment would activate function senescent mice suppression Foxo1-associated pro-apoptotic signalling. Our echocardiographic measurements indicated systolic measured as fractional shortening ejection fraction was significantly reduced aged when compared with young mice. These reductions, however, were not observed resveratrol-treated hearts. Ageing deacetylase activity, but protein abundance This reduction accompanied increased acetylation Foxo1 transcription factor transactivation its target, Bim. Subsequent analyses p53, Bax apoptotic DNA fragmentation up-regulated heart contrast, restored activity suppressed elevations acetylation, Bim parallel, also attenuated ageing-induced collagen markers oxidative damage including 4HNE nitrotyrosine. conclusion, these novel data demonstrate mitigates deacetylation mechanism represses Foxo1-Bim-associated