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 proinflammatory immune cells. Not only adipocytes and preadipocytes, 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.

Dietary intervention improves health metrics and life expectancy of the genetically obese DU6 (Titan) mouse

“…Such genes were also shown to be downregulated in the mouse liver upon high-fat diet 24 . Similarly, genes involved in mitochondrial organization and function were downregulated in 19-21-weekold Titan mice, which may hint towards altered mitochondrial activity in older Titan mice 58 . Altogether, these findings suggest an altered liver metabolism in Titan compared to control mice, along with their obese phenotype and shorter lifespan.…”

“…Titan mice also showed whitening of BAT, and ectopic fat in the pancreas, both being linked to obesity and MetS 22,53 . Increased pancreatic fat might have implications for the onset of type 2 diabetes 54 , which is frequently associated with insulin resistance 21 .Importantly, obesity is known to be associated with reduced life expectancy and various conditions related to aging, such as inflammation [55][56][57][58][59][60] . Indeed, we found that Titan mice exhibited a shorter lifespan compared to control mice, which is in line with a recent study showing that female Titan mice show a reduced lifetime fecundity compared to the unselected control mice 61 .…”

Macrophage Related Chronic Inflammation in Non-Healing Wounds

“…Obesity and aging share many common traits in term of immunity and metabolism ( 91 , 92 ). Several studies showed that obesity modifies the composition of adipose tissue in BM and restrains the generation of osteoblastic cells from mesenchymal progenitors, thereby affecting BM homeostasis.…”

B Cells with a Senescent-Associated Secretory Phenotype Accumulate in the Adipose Tissue of Individuals with Obesity

“…Senescent cells accumulate in the body during aging, promote tissue degeneration and malignant transformation, and lead to the development of inflammatory-based age-associated diseases [ 5 , 6 ]. Senescent cells also accumulate in the adipose tissue (AT) of mice and humans, and secrete multiple SASP factors that have been shown to induce cell death, increased local and systemic inflammation and recruitment of immune cells, leading to AT dysfunction, insulin resistance and type-2 diabetes [ 7 , 8 , 9 ].…”