POTENTIAL OF SGLT2 INHIBITORS TO INFLUENCE CELL AGING PATHWAYS

Abstract

 Cellular senescence is a fundamental biological process characterized by irreversible cell-cycle arrest, altered chromatin structure, mitochondrial dysfunction, metabolic reprogramming, and secretion of pro-inflammatory mediators collectively known as the senescence-associated secretory phenotype (SASP). Although senescence serves protective functions in tumor suppression and tissue repair, the chronic accumulation of senescent cells contributes to aging and the development of chronic diseases such as cardiovascular disease, chronic kidney disease, metabolic syndrome, and frailty.SGLT2 inhibitors—empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin—were originally approved for glycemic control by promoting renal glucose excretion. However, large clinical trials have shown their ability to reduce cardiovascular events, improve heart failure outcomes, and slow chronic kidney disease progression in both diabetic and non-diabetic individuals. These wide-ranging benefits have accelerated interest in understanding whether SGLT2 inhibitors influence aging pathways, including cellular senescence.Emerging evidence indicates that SGLT2 inhibitors may act as senomorphics (agents that suppress SASP and senescent cell activity) or even senolytics (agents that facilitate senescent cell clearance)[2]. Their effects on oxidative stress, inflammation, mitochondrial integrity, and autophagy intersect with central mechanisms of cellular aging, suggesting an important therapeutic potential beyond diabetes management.