On Adipose Tissue Inflammation in Aging
One of the more important reasons not to carry excess fat tissue is that it becomes ever more inflammatory with age, particularly visceral fat. Chronic, unresolved inflammation is a feature of aging that accelerates the onset and progress of all of the common fatal age-related conditions. To the degree that excess fat tissue contributes to this inflammation, one might argue that it is accelerating aging. The contribution of fat to this form of immune system dysfunction is a two-way street, as noted here. In part, the contribution of fat to inflammation becomes worse with age because of harmful changes in the immune system itself.
Adipose tissue is essential for age-related dysfunction such as metabolic diseases, while aging can also generate multiple effects on adipose tissue, including redistribution of deposits and composition, adipose tissue plasticity reduction, senescent cell accumulation and inflammaging. Among them, adipose tissue inflammation is the most important. This chronic inflammation is usually promoted by senescent cell/dead cell accumulation, adipocyte hypertrophy, free fatty acids (FFAs) and lipopolysaccharide (LPS), and immune cell dysregulation.
Various cellular and molecular mechanisms regulate adipose tissue inflammaging. Immune cells are recruited to adipose tissue by different chemokines, and undergo tremendous changes in both their numbers and characteristics during aging. Proinflammatory signaling pathways, including the JAK/STAT, Wnt/β-catenin, NF-κB, and MAPK signaling pathways, control the process of adipose tissue inflammaging in different way. Indeed, Increased inflammaging in aging impacts adipose tissue, leading to adipose tissue dysfunction and ectopic lipid accumulation, further impacting the overall health status.
Systemic diseases, such as type II diabetes, cardiovascular disease, and cancer, are somewhat caused by adipose tissue inflammation. Since adipose tissue inflammaging plays pivotal roles, emerging anti-aging interventions have recently been developed targeting adipose tissue. In this review, we summarize the latest approaches that can extend healthy lifespan and delay the onset of age-related diseases including caloric restriction, senotherapeutics, immune therapies, and other strategies targeting adipose tissue inflammaging related signaling pathways. Further research may need to focus on whether suppressing the inflammatory response in adipose tissue can reverse the senescent phenotype, an approach that may identify new targets to relieve aging-associated complications.