Acceleration of β Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes.

ABSTRACT: Type 2 diabetes (T2D) is an age-related disease. Although changes in function and proliferation of aged β cells resemble those preceding the development of diabetes, the contribution of β cell aging and senescence remains unclear. We generated a β cell senescence signature and found that insulin resistance accelerates β cell senescence leading to loss of function and cellular identity and worsening metabolic profile. Senolysis (removal of senescent cells), using either a transgenic INK-ATTAC model or oral ABT263, improved glucose metabolism and β cell function while decreasing expression of markers of aging, senescence, and senescence-associated secretory profile (SASP). Beneficial effects of senolysis were observed in an aging model as well as with insulin resistance induced both pharmaco

SUBMITTER: Aguayo-Mazzucato C 

PROVIDER: S-EPMC6610720 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature