Reviewing the Role of Cellular Senescence in Metabolic Disease
Senescent cells accumulate with age throughout the body. In youth the immune system promptly removes senescent cells, but this clearance slows with advancing age, leading to a growing population of lingering senescent cells. Senescent cells cease replicating and devote their efforts to the production of pro-growth, pro-inflammatory signals that become disruptive to tissue structure and function. Thus a population of senescent cells acts to actively maintain a degraded state of tissue, and their removal is immediately beneficial. Mouse studies show compelling, rapid reversals of age-related disease and extended life span resulting from the use of senolytic therapies to clear senescent cells. Of note, metabolic diseases associated with obesity, and which become worse with old age, appear involve senescent cells in a prominent role. One of the reasons that obesity is bad for health is that it accelerates the accumulation of senescent cells.
Cellular senescence refers to a stable non-proliferative state that cells enter in response to various stresses. This process is implicated in the development of various age-related diseases, including body aging, tumors, and senile dementia. Recently, an increasing number of researchers have focused on the relationship between cellular senescence and metabolic disorders. First, key cells involved in metabolic regulation undergo age-related changes. In patients with diabetes, the proportion of aging β-cells in the pancreas increases, and eliminating these cells can effectively prevent the onset and development of diabetes. In adipose tissue, aging adipose precursor cells promote insulin resistance in adipose cells. In addition, aging endothelial cells contribute to the formation of atherosclerotic plaques and increase plaque instability.
Second, the secretory phenotype of senescent cells undergoes significant changes, resulting in the production of a variety of pro-inflammatory factors. This phenomenon is referred to as the Senescence-Associated Secretory Phenotype (SASP). As a result, the continued accumulation of senescent cells can cause chronic inflammation. This chronic inflammatory response is considered as an important contributor to metabolic diseases. Thus, senescent cells may contribute to the onset and development of metabolic diseases, including diabetes, in various ways.
Aging intervention therapies targeting the clearance of senescent cells via senolytics or the modulation of their SASP via senomorphics have increasingly attracted the attention of researchers investigating their potential role in metabolic diseases. This paper reviews the relationship between metabolic diseases and cellular senescence and discusses the role of cellular senescence in these disorders, thereby providing new insights into their treatment.