17β-estradiol delays cardiac aging through suppressing the methylation of Beclin1 in a murine model

作者：Lili Ye, Xiaoyi Shi, Tianming Deng, Jun Zhao, Tianjie Wu, Jingrong Chen · 发表于：Research Square · 年份：2023 · DOI：10.21203/rs.3.rs-2793118/v1 · 研究领域：Advanced Glycation End Products research、Autophagy in Disease and Therapy、Genetics, Aging, and Longevity in Model Organisms

Abstract Cardiac endogenous senescence will gradually change and aggravate with age. Recent research showed that 17β-estradiol (17β-E2), an estrogen with numerous biological activities including the prevention of vascular senescence. However, how 17β-E2 against cardiac aging is still unknown. This work addressed the underlying mechanism with regard to Beclin1 and autophagy activity to better understand the anti-senescent effect of 17β-E2 on a well-established animal model of cardiac aging. The findings demonstrated that cardiac aging mice treated with 17β-E2 had substantially improved heart function. By RNA-sequencing and Gene Set Enrichment Analysis (GSEA) analysis, the autophagy signaling pathway was further enriched in the myocardial tissue of cardiac aging mice treated with 17β-E2, and we also discovered that 17β-E2 obviously suppress the methylation of Beclin1 promoter region, which mediate the activation of autophagy signal. Overall, our data showed that 17β-E2's anti-senescent effect on cardiac aging mice was mediated by the crucial suppression of methylation in the Beclin1 promoter area and subsequent activation of the autophagy signal, which may present a possible therapeutic approach to prevent cardiac aging.