Adipose tissue aging is regulated by an altered immune system

Abstract

Adipose tissue is a widely distributed organ that plays a critical role in age-related physiological dysfunctions as an important source of chronic sterile low-grade inflammation. Adipose tissue undergoes diverse changes during aging, including fat depot redistribution, brown and beige fat decrease, functional decline of adipose progenitor and stem cells, senescent cell accumulation, and immune cell dysregulation. Specifically, inflammaging is common in aged adipose tissue. Adipose tissue inflammaging reduces adipose plasticity and pathologically contributes to adipocyte hypertrophy, fibrosis, and ultimately, adipose tissue dysfunction. Adipose tissue inflammaging also contributes to age-related diseases, such as diabetes, cardiovascular disease and cancer. There is an increased infiltration of immune cells into adipose tissue, and these infiltrating immune cells secrete proinflammatory cytokines and chemokines. Several important molecular and signaling pathways mediate the process, including JAK/STAT, NFκB and JNK, etc. The roles of immune cells in aging adipose tissue are complex, and the underlying mechanisms remain largely unclear. In this review, we summarize the consequences and causes of inflammaging in adipose tissue. We further outline the cellular/molecular mechanisms of adipose tissue inflammaging and propose potential therapeutic targets to alleviate age-related problems.

Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils

“…Alternatively, intrinsic sex differences in immune system have been demonstrated as well ( Chen et al, 2021a ; Singer et al, 2015 ) that are dependent on sex chromosome complement and/or Xist expression ( Syrett et al, 2018 ; Pyfrom et al, 2021 ), and RELMα may be regulated by these as well. Additionally, aging-mediated increase in inflammation (including of adipose tissue, recently reviewed in Zhang et al, 2023 ), may also occur via changes in RELMα levels. Our studies used young but developmentally mature mice (4–6 weeks old when placed on diet, 18 weeks old at sacrifice), and future work on aged mice would be needed to investigate aging-mediated inflammation.…”

The 24-h profile of the DNA repair enzyme 8-oxoguanine glycosylase 1 (OGG1) is associated with age, TNF-α, and waist circumference in healthy adults

“…Inflammaging occurs in aged adipose tissue, where it contributes to adipocyte hypertrophy and dysfunction; there is also an increased infiltration of immune cells in adipose tissue and these immune cells secreted proinflammatory cytokines [ 51 ]. Animal studies showed that adipose-tissue derived TNF-α (AT-TNF) activity was elevated in older animals, while AT-TNF protein levels where higher in young animals, suggesting that they may secrete an inhibitor that reduces AT-TNF activity [ 52 ].…”

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

“…According to Jin and Bi[ 66 ], a microarray study shows that HBV significantly increases the expression of Bcl-2-like protein 11 in HBV-specific CD8+ T cells, pointing to a critical mechanism for CD8+ T cell depletion during CHB infection. Inhibitory receptors such as PD-1, CTLA-4, CD244 (2B4), Tim-3, and lymphocyte activation gene 3 are present on exhausted HBV-specific CD8+ T cells, and these receptors closely resemble the transcriptional patterns of CD8+ T cells[ 66 , 77 ].…”