SGLT2 inhibitors as a novel senotherapeutic approach

Abstract

Cellular senescence is the permanent cessation of cell proliferation and growth. Senescent cells accumulating in tissues and organs with aging contribute to many chronic diseases, mainly through the secretion of a pro-inflammatory senescence-associated secretory phenotype (SASP). Senotherapeutic (senolytic or senomorphic) strategies targeting senescent cells or/and their SASP are being developed to prolong healthy lifespan and treat age-related pathologies. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of anti-diabetic drugs that promote the renal excretion of glucose, resulting in lower blood glucose levels. Beyond their glucose-lowering effects, SGLT2 inhibitors have demonstrated protective effects against cardiovascular and renal events. Moreover, SGLT2 inhibitors have recently been associated with the inhibition of cell senescence, making them a promising therapeutic approach for targeting senescence and aging. This review examines the latest research on the senotherapeutic potential of SGLT2 inhibitors.