Senescence in obesity

Obesity results in multiple cellular stresses that induce cellular senescence, leading to senescent cell accumulation in adipose tissue as well as other organs. Although senescent cells represent a very small percentage of cells at any given tissue, the 30%-70% of senescent cells with a senescence-associated secretory phenotype (SASP) can exert substantial effects locally and systemically. Senescent cells are implicated in many consequences of obesity, including metabolic dysfunction, hepatic steatosis, and neurocognitive dysfunction, among others. Adipose tissue, a metabolically active tissue involved in lipid storage, endocrine signaling, and immunity, can be a major reservoir of senescent cells, even in lean individuals. Removal of senescent cells with senolytic drugs or blunting their effects with SASP inhibitors (senomorphics) can alleviate obesity-induced dysfunction in several tissues. Thus, senescent cells represent a promising therapeutic target for delaying, preventing, or treating the negative consequences of obesity.