The role of adipose tissue senescence in obesity- and ageing-related metabolic disorders.

Adipose tissue as the largest energy reservoir and endocrine organ is essential for maintenance of systemic glucose, lipid and energy homeostasis, but these metabolic functions decline with ageing and obesity. Adipose tissue senescence is one of the common features in obesity and ageing. Although cellular senescence is a defensive mechanism preventing tumorigenesis, its occurrence in adipose tissue causatively induces defective adipogenesis, inflammation, aberrant adipocytokines production and insulin resistance, leading to adipose tissue dysfunction. In addition to these paracrine effects, adipose tissue senescence also triggers systemic inflammation and senescence as well as insulin resistance in the distal metabolic organs, resulting in Type 2 diabetes and other premature physiological declines. Multiple cell types including mature adipocytes, immune cells, endothelial cells and progenitor cells gradually senesce at different levels in different fat depots with ageing and obesity, highlighting the heterogeneity and complexity of adipose tissue senescence. In this review, we discuss the causes and consequences of adipose tissue senescence, and the major cell types responsible for adipose tissue senescence in ageing and obesity. In addition, we summarize the pharmacological approaches and lifestyle intervention targeting adipose tissue senescence for the treatment of obesity- and ageing-related metabolic diseases.