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

Area of Science:

• Gerontology
• Pharmacology
• Cell Biology

Background:

• Aging-related sarcopenia and endothelial senescence are critical health concerns in the elderly.
• Current therapeutic options for these conditions are limited, necessitating novel treatment strategies.

Purpose of the Study:

• To investigate the therapeutic effects of Semaglutide (Sema) on D-galactose-induced aging-related sarcopenia and endothelial cell senescence.
• To elucidate the underlying molecular mechanisms of Sema's action in these aging models.

Main Methods:

• Establishment of D-galactose-induced mouse models of aging and human aortic endothelial cells (HAEC) models.
• Assessment of therapeutic efficacy using grip strength tests, ELISA for inflammatory markers (IL-1β, TNF-α), and immunohistochemistry.
• Evaluation of endothelial function and senescence markers.

Main Results:

• Semaglutide significantly improved grip strength in D-galactose-induced mice.
• Sema treatment reduced serum levels of pro-inflammatory cytokines IL-1β and TNF-α.
• Sema alleviated endothelial cell senescence and improved endothelial function, potentially via SIRT1 upregulation and cGAS-STING pathway inhibition.

Conclusions:

• Semaglutide demonstrates significant therapeutic potential for aging-related sarcopenia.
• Sema exhibits protective effects against aortic endothelial senescence, suggesting broader anti-aging benefits.
• This research provides novel insights into Semaglutide's mechanisms and supports its potential clinical application in age-related diseases.