Senolytics could provide Novel Therapy for Diabetes

Type 2 diabetes is an age-related disease characterized by a progressive decrease in β cell mass and function that leads to a failure to produce enough insulin to maintain a normal blood glucose level.

With age, accumulation of dysfunctional senescent β cells likely contributes to impaired glucose tolerance and diabetes. However, the specific contribution of β cell aging and senescence to diabetes is poorly understood, and therapies that target the aging aspect of the disease are virtually non-existent.

This study investigated the link between β cell aging and the development of diabetes. They found that applying metabolic stressors, such as the insulin receptor antagonist S961 to induce insulin resistance, accelerated the expression of aging and senescence markers (e.g. p16Ink4a). Moreover, treatment with an oral senolytic compound, ABT263, ameliorated hyperglycemia and improved the β cell gene expression profile in mouse models.

Similarly, in human β cells, the load of senescent cells increased with age and diabetes, and senescent cells were also found to over express p16Ink4a. This suggests that senolysis could be a potential therapy for inhibiting the progression of type II diabetes.