SGLT2 inhibition eliminates senescent cells and alleviates pathological aging

Authors
Katsuumi, Goro, Shimizu, Ippei, Suda, Masayoshi, Yoshida, Yohko, Furihata, Takaaki, Joki, Yusuke, Hsiao, Chieh-Lun, Jiaqi, Liang, Fujiki, Shinya, Abe, Manabu, Sugimoto, Masataka, Soga, Tomoyoshi, Minamino, Tohru


Lab

Journal
Nature Aging

Abstract
It has been reported that accumulation of senescent cells in various tissues contributes to pathological aging and that elimination of senescent cells (senolysis) improves age-associated pathologies. Here, we demonstrate that inhibition of sodium-glucose co-transporter 2 (SGLT2) enhances 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, but normalization of plasma glucose by insulin treatment had no effect on senescent cells. Canagliflozin extended the lifespan of mice with premature aging even when treatment was started in middle age. Metabolomic analyses revealed that short-term treatment with canagliflozin upregulated 5-aminoimidazole-4-carboxamide-1-Beta-d-ribofuranoside, enhancing immune-mediated clearance of senescent cells by downregulating expression of programmed cell death-ligand 1. These findings suggest that inhibition of SGLT2 has an indirect senolytic effect by enhancing endogenous immunosurveillance of senescent cells. Katsuumi, Shimizu, Suda et al. report that SGLT2 inhibition reduces the senescence burden and alleviates aging traits in mice. The authors demonstrate an indirect mechanism of senescent cell removal, through enhancing immunosurveillance.

Keywords/Topics
inhibition;eliminates;senescent;cells;alleviates;pathological;aging;reported;accumulation;various

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://www.nature.com/articles/s43587-024-00642-y

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