Pancreatic β-Cell Senescence: Mechanisms and Association with Diabetes

Abstract

Senescence occurs as a part of the cellular response to different stressors. With increasing age, continuous exposure to stressors leads to age-induced senescence. Pancreatic β-cell proliferation and glucose homeostasis also decrease with age, which results in a decrease in β cell mass and, eventually, the possible development of diabetes. This process is mediated through impaired cell cycle regulators, along with specific increases in cell cycle inhibitors, telomere shortening, and defective DNA repair mechanisms. Diabetes contributes to β-cell senescence through hyperglycaemia, dyslipidaemia, oxidative stress, and inflammation. β cells isolated from patients with Type 2 diabetes mellitus have been shown to have senescence markers, such as senescence-associated secretory phenotype genes and β-galactosidase. In this paper, the authors discuss the mechanisms of cellular senescence, how senescence is impacted by the diabetic microenvironment, and the possible mechanisms and factors contributing to β-cell senescence.