Aging and adipose tissue: potential interventions for diabetes and regenerative medicine

Abstract

Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies.

Keywords: Adipose Tissue; Aging; Cellular Senescence; Insulin Resistance; Preadipocyte; Stem Cell.

Figure 1. Adipose tissue changes with aging

With aging, adipose tissue undergoes numerous changes, affecting distribution, inflammatory status, progenitor function, senescent cell burden, deposition of lipid in ectopic sites, adipose-derived hormone production and action, miRNA processing, and brown and beige adipose function.

Figure 2. Possible points of intervention for adipose-derived stem cell therapies in aged individuals

Adipose-derived stem cells are becoming increasingly utilized in regenerative medicine. Many patients who would benefit from such therapies are elderly, and the effects of aging on adipose tissue and progenitor function may reduce efficacy of these therapies. This may be due to both inherent dysfunction of isolated progenitor cells and the aged microenvironment of the recipient. Strategies to mitigate effects of aging on these cells may need to be used to optimize their use in older individuals. Points at which such strategies could be employed include (A) before isolating progenitor cells, (B) in vitro before returning cells to the patient, and (C) in allogeneic applications, administration of age-modifying therapy to the recipient before transplantation of young or revitalized progenitor cells.