Figure 3. Cell senescence as likely mediator of the bidirectional relationship between IR and hyperinsulinemia.

Senescent cells accumulate in multiple tissues in obesity, T2D, and NAFLD/NASH, including AT and the liver. Increased CS in those tissues may cause IR, which, in turn, leads to hyperinsulinemia. Hyperinsulinemia, on the other hand, may induce senescence in both adipocytes and liver cells, contributing to an increase in CS burden in the AT and liver. Thus, CS may enable and fuel a vicious cycle between IR and hyperinsulinemia, which plays a considerable role in the development of several metabolic diseases and their consequences.