SGLT2 inhibition eliminates senescent cells and alleviates pathological aging. A study demonstrates that inhibiting SGLT2 enhances the clearance of senescent cells, thereby ameliorating age-associated phenotypic changes. In a mouse model of dietary obesity, short-term treatment with the SGLT2 inhibitor canagliflozin reduced the senescence load in visceral adipose tissue and improved adipose tissue inflammation and metabolic dysfunction. Canagliflozin extended the lifespan of mice with premature aging even when treatment was started in middle age. Metabolomic analyses revealed that canagliflozin upregulated 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside, enhancing immune-mediated clearance of senescent cells by downregulating expression of programmed cell death-ligand 1. These findings suggest that SGLT2 inhibition has an indirect senolytic effect by enhancing endogenous immunosurveillance of senescent cells. Senescent cells accumulate in tissues and contribute to pathological aging. Elimination of senescent cells (senolysis) improves age-associated pathologies. SGLT2 inhibition may have a senolytic effect by enhancing endogenous immunosurveillance of senescent cells. Canagliflozin treatment significantly reduced senescence-like changes in visceral adipose tissue and other tissues, including reduction of senescence-associated β-galactosidase activity and decreased expression of negative cell-cycle regulators. Canagliflozin treatment also led to a significant improvement in HFD-induced senescence-like changes in gWAT and other tissues. The study also found that canagliflozin treatment caused a decrease in crown-like structures and reduced oxidative stress. The study also found that SGLT2 inhibition affects programmed cell death-ligand 1 expression by senescent cells. Senescent cells activate the immune system by secreting SASP factors. The activated immune system is believed to maintain tissue homeostasis by removing senescent cells. In aging and pathological conditions, this removal mechanism becomes dysfunctional (anergy) and senescent cells continue to accumulate in tissues. The increased secretion of SASP factors triggers chronic inflammation, which is thought to be involved in the development of aging-related diseases. SGLT2 inhibition may have a senolytic effect by enhancing endogenous immunosurveillance of senescent cells. The study also found that SGLT2 inhibition affects programmed cell death-ligand 1 expression by senescent cells. Senescent cells that accumulate in tissues activate the immune system by secreting SASP factors. The activated immune system is believed to maintain tissue homeostasis by removing senescent cells. In aging and pathological conditions, this removal mechanism becomes dysfunctional (anergy) and senescent cells continue to accumulate in tissues. The increased secretion ofSGLT2 inhibition eliminates senescent cells and alleviates pathological aging. A study demonstrates that inhibiting SGLT2 enhances the clearance of senescent cells, thereby ameliorating age-associated phenotypic changes. In a mouse model of dietary obesity, short-term treatment with the SGLT2 inhibitor canagliflozin reduced the senescence load in visceral adipose tissue and improved adipose tissue inflammation and metabolic dysfunction. Canagliflozin extended the lifespan of mice with premature aging even when treatment was started in middle age. Metabolomic analyses revealed that canagliflozin upregulated 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside, enhancing immune-mediated clearance of senescent cells by downregulating expression of programmed cell death-ligand 1. These findings suggest that SGLT2 inhibition has an indirect senolytic effect by enhancing endogenous immunosurveillance of senescent cells. Senescent cells accumulate in tissues and contribute to pathological aging. Elimination of senescent cells (senolysis) improves age-associated pathologies. SGLT2 inhibition may have a senolytic effect by enhancing endogenous immunosurveillance of senescent cells. Canagliflozin treatment significantly reduced senescence-like changes in visceral adipose tissue and other tissues, including reduction of senescence-associated β-galactosidase activity and decreased expression of negative cell-cycle regulators. Canagliflozin treatment also led to a significant improvement in HFD-induced senescence-like changes in gWAT and other tissues. The study also found that canagliflozin treatment caused a decrease in crown-like structures and reduced oxidative stress. The study also found that SGLT2 inhibition affects programmed cell death-ligand 1 expression by senescent cells. Senescent cells activate the immune system by secreting SASP factors. The activated immune system is believed to maintain tissue homeostasis by removing senescent cells. In aging and pathological conditions, this removal mechanism becomes dysfunctional (anergy) and senescent cells continue to accumulate in tissues. The increased secretion of SASP factors triggers chronic inflammation, which is thought to be involved in the development of aging-related diseases. SGLT2 inhibition may have a senolytic effect by enhancing endogenous immunosurveillance of senescent cells. The study also found that SGLT2 inhibition affects programmed cell death-ligand 1 expression by senescent cells. Senescent cells that accumulate in tissues activate the immune system by secreting SASP factors. The activated immune system is believed to maintain tissue homeostasis by removing senescent cells. In aging and pathological conditions, this removal mechanism becomes dysfunctional (anergy) and senescent cells continue to accumulate in tissues. The increased secretion of