Adipose tissue, immune aging, and cellular senescence.

Abstract

Obesity represents a serious health problem as it is rapidly increasing worldwide. Obesity is associated with reduced healthspan and lifespan, decreased responses to infections and vaccination, and increased frequency of inflammatory conditions typical of old age. Obesity is characterized by increased fat mass and remodeling of the adipose tissue (AT). In this review, we summarize published data on the different types of AT present in mice and humans, and their roles as fat storage as well as endocrine and immune tissues. We review the age-induced changes, including those in the distribution of fat in the body, in abundance and function of adipocytes and their precursors, and in the infiltration of immune cells from the peripheral blood. We also show that cells with a senescent-associated secretory phenotype accumulate in the AT of mice and humans with age, where they secrete several factors involved in the establishment and maintenance of local inflammation, oxidative stress, cell death, tissue remodeling, and infiltration of pro-inflammatory immune cells. Not only adipocytes and pre-adipocytes but also immune cells show a senescent phenotype in the AT. With the increase in human lifespan, it is crucial to identify strategies of intervention and target senescent cells in the AT to reduce local and systemic inflammation and the development of age-associated diseases. Several studies have indeed shown that senescent cells can be effectively targeted in the AT by selectively removing them or by inhibiting the pathways that lead to the secretion of pro-inflammatory factors.