(selected excerpts below)In recent work [2,3] we showed that insulin resistance induced the expression of aging markers, suggesting that β-cell aging could accelerate the progression toward diabetes...Along these lines, we demonstrated that senescent β-cells downregulated hallmark identity genes, upregulated disallowed genes, and secreted proinflammatory cytokines [2]...We established two models of insulin resistance in mice: one using the delivery of the insulin receptor antagonist S961, and the other using a more physiologically representative high fat diet. In both cases, the metabolic stress increased the number of senescent β-cells while impairing glucose tolerance. Aging and SASP genes were also upregulated, but after insulin resistance was stopped, gene expression returned to healthy levels. This suggests that there might be critical windows during which β-cell senescence may be reversible. These results were consistent with experiments on human β-cells, in which senescence increased with age, body mass index and in the presence of T2D.Additionally, we found that the targeted deletion of senescent cells, or senolysis, in mice improved β-cell function, reduced blood glucose levels, and restored healthy expression levels of aging and SASP genes. Our findings highlight the transformative therapeutic potential of senolytic drugs in restoring β-cell function among T2D patients.