Taken together the up to date researches, we draw a conclusion that with advancing age, the pathological alterations of pancreatic β cells are supposed to be the key contributor to age-related T2D, and the decreased proliferation and regeneration potential, disturbed transcriptome and proteostasis, increased senescent cell accumulation and the influence of systemic environmental stress may lead to the loss of functional β cell mass and ultimately deficient insulin secretion and insulin action (Figure 2). The gene discussed is INS; the disease is type 2 diabetes mellitus.