A human and mouse subpopulation of senescent β-cells induces pathologic dysfunction through targetable paracrine signaling.

ABSTRACT: Cellular senescence is a stress response mechanism marked by irreversible growth arrest, upregulation of antiapoptotic pathways, loss of cellular function, and remodelling of the cellular secretory profile. In both humans and mice, pancreatic β-cells undergo senescence with age and insulin resistance. Targeted removal of senescent cells in mouse models of diabetes improves glucose homeostasis, demonstrating the role β-cell senescence in diabetes progression. In contrast, β-cell senescence also promotes immune surveillance, promoting β-cell survival and function. Thus, a better understanding of senescent cells' phenotypic and functional heterogeneity is needed to develop effective therapeutic strategies. Herein, we show that subpopulations of senescent β-cells in mice and humans, which were

SUBMITTER: Iwasaki K 

PROVIDER: S-EPMC12247971 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature