INTRODUCTION: Cardiac endogenous senescence will gradually change and aggravate with age. Recent research showed that 17��-estradiol (17��-E2), an estrogen with numerous biological activities including the prevention of vascular senescence. However, how 17��-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 17��-E2 on a well-established animal model of cardiac aging.
MATERIAL AND METHODS: In this study, an aging model in female mice was established using d-galactose and ovariectomy. Cardiac function was evaluated by echocardiography, RNA-seq was performed to analyze the gene expression profiles of myocardial tissues from 17��-E2 treated mice. Additionally,The levels of Beclin1, LC3, P62, and ATG5 in myocardial tissues were assessed using qPCR and Western blotting. Methylation levels of the Beclin1 promoter region in myocardial tissues were determined by MSP and BSP.
RESULTS: The findings demonstrated that cardiac aging mice treated with 17��-E2 had improved heart function. 17��-E2 restored EF(increase 1.25-fold) and FS(increase 1.2-fold) to near-normal levels. 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 17��-E2, and we also discovered that 17��-E2 suppress the methylation of Beclin1 promoter region, which mediate the activation of autophagy signal.
CONCLUSIONS: Overall, our data showed that 17��-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.
