Aging Leukocytes and the Inflammatory Microenvironment of the Adipose Tissue

Abstract

Age-related immunosenescence, defined as an increase in inflammaging and the decline of the immune system, leads to tissue dysfunction and increased risk for metabolic disease. The elderly population is expanding, leading to a heightened need for therapeutics to improve health span. With age, many alterations of the immune system are observed, including shifts in the tissue-resident immune cells, increased expression of inflammatory factors, and the accumulation of senescent cells, all of which are responsible for a chronic inflammatory loop. Adipose tissue and the immune cell activation within are of particular interest for their well-known roles in metabolic disease. Recent literature reveals that adipose tissue is an organ in which signs of initial aging occur, including immune cell activation. Aged adipose tissue reveals changes in many innate and adaptive immune cell subsets, revealing a complex interaction that contributes to inflammation, increased senescence, impaired catecholamine-induced lipolysis, and impaired insulin sensitivity. Here, we will describe current knowledge surrounding age-related changes in immune cells while relating those findings to recent discoveries regarding immune cells in aged adipose tissue.

Figure 1

Aging of the mouse immune system. Shown is a timeline to compare mouse and human aging, along with broad phases of life: juvenile, mature adult, middle-aged, and old. The identified changes in the immune system of mice are listed at the top, and the typical comparison for mouse experiments are highlighted in brackets. Created in BioRender (BioRender.com).

Figure 2

Aged immune cells drive AT dysfunction. Shown is a schematic to describe the tissue maintaining immune cells within the AT in young, lean conditions (left side) and the accumulation of inflammatory immune cells in aged AT. The net sum of the changes in the tissue-maintaining and inflammatory cells leads to an accumulation of inflammation and loss of adipocyte function. Pre-adipocytes accumulate features of senescence, secrete a SASP, and tend to differentiate into fibroblasts as opposed to lipid-storing adipocytes. Adipocytes show reduced catecholamine and insulin signaling. A question mark indicates that age-related changes are unknown. Arrows indicate the direction of change compared with young mice. Changes in both male and female mice are included in this summary. Breg, regulatory B cell; Eo, eosinophils; GzmB, granzyme B; ILC2, innate lymphoid cell; Mac, macrophage. Created in BioRender (BioRender.com).