Semaglutide ameliorates aortic endothelial cell dysfunction in sarcopenia through the SIRT1/cGAS-STING signaling axis.

Abstract

Sarcopenia associated with aging is a significant health issue affecting the quality of life in the elderly, yet research on effective treatments remains insufficient. This study aims to investigate the therapeutic effects and mechanisms of Semaglutide (Sema) in D-gal-induced aging-related sarcopenia and endothelial cell senescence. By establishing D-gal-induced mouse models and human aortic endothelial cells (HAEC), and employing methods such as grip strength tests, ELISA, and immunohistochemistry, the therapeutic efficacy and underlying mechanisms of Sema were systematically evaluated. The results demonstrated that Sema significantly improved grip strength in D-gal-induced mice and reduced serum levels of IL-1β and TNF-α, indicating its protective role against sarcopenia. Furthermore, Sema effectively alleviated endothelial cell senescence and improved endothelial function, with the underlying mechanisms potentially involving the upregulation of SIRT1 expression and inhibition of the cGAS-STING signaling pathway activation. This study systematically reveals, for the first time, the therapeutic potential of Sema in aging-related sarcopenia, especially its protective effect against aortic endothelial senescence, providing new perspectives and evidence for its clinical application.