Across aging, adipose tissue (AT) changes its quantity and distribution: AT becomes dysfunctional with an increase in production of inflammatory peptides, a decline of those with anti-inflammatory activity and infiltration of macrophages. Adipose organ dysfunction may lead to age-related metabolic alterations. Aging is characterized by an increase in adiposity and a decline in brown adipose tissue (BAT) depots and activity, and UCP1 expression. There are many possible links to age-associated involution of BAT, including the loss of mitochondrial function, impairment of the sympathetic nervous system, age-induced alteration of brown adipogenic stem/progenitor cell function and changes in endocrine signals. Aging is also associated with a reduction in beige adipocyte formation. Beige adipocytes are known to differentiate from a sub-population of progenitors resident in white adipose tissue (WAT); a defective ability of progenitor cells to proliferate and differentiate has been hypothesized with aging. The loss of beige adipocytes with age may be caused by changes in trophic factors in the adipose tissue microenvironment, which regulate progenitor cell proliferation and differentiation. This review focuses on possible mechanisms involved in the reduction of BAT and beige activity with aging, along with possible targets for age-related metabolic disease therapy.

Association between inflammatory markers and intermuscular adipose tissue (IMAT) has been reported. We hypothesized that subclinical inflammation of adipose tissue surrounding and infiltrating muscle could be related to the metabolic and functional abnormalities of the “aging muscle.” In 20 healthy elderly men undergoing elective vertebral surgery, IMAT within erector spinae was evaluated by magnetic resonance imaging and body composition by dual-energy x-ray absorptiometry. Fasting glucose, insulin, high-sensitive C-reactive protein (hs-CRP), leptin, adiponectin, and interleukin 6 (IL-6) were measured, and insulin resistance was estimated by homeostasis model assessment (HOMA) index. In subcutaneous adipose tissue (SAT) biopsies near the erector spinae, quantification of gene expression was performed. IMAT showed a significant association with body mass index and total and regional body fat, even after adjustment for age. Insulin, HOMA, and leptin were significantly correlated with IMAT, whereas hs-CRP presented an association of borderline significance. IL-6 expression in SAT was significantly associated with IMAT; IL-6 messenger RNA (mRNA) was negatively associated with adiponectin and peroxisome proliferator–activated receptor gamma expression. In multivariate regression analysis, 68% of IMAT variance was explained by fat mass and age, independent of waist circumference, leptin, HOMA, and IL-6 mRNA. IMAT was primarily related to age and total body adiposity; subclinical inflammation in fat significantly contributes to IMAT.

Multiple lines of evidence suggest that cytokines influence different physiologic functions of skeletal muscle cells, including anabolic and cataboli