Aging and regional differences in fat cell progenitors - a mini-review

Abstract

Fat mass and fat tissue distribution change dramatically throughout life. In old age, fat becomes dysfunctional and is redistributed from subcutaneous to intra-abdominal visceral depots as well as other ectopic sites, including bone marrow, muscle and the liver. These changes are associated with increased risk of metabolic syndrome. Fat tissue is a nutrient storage, endocrine and immune organ that undergoes renewal throughout the lifespan. Preadipocytes, which account for 15-50% of cells in fat tissue, give rise to new fat cells. With aging, declines in preadipocyte proliferation and differentiation likely contribute to increased systemic exposure to lipotoxic free fatty acids. Age-related fat tissue inflammation is related to changes that occur in preadipocytes and macrophages in a fat depot-dependent manner. Fat tissue inflammation frequently leads to further reduction in adipogenesis with aging, more lipotoxicity and activation of cellular stress pathways that, in turn, exacerbate inflammatory responses of preadipocytes and immune cells, establishing self-perpetuating cycles that lead to systemic dysfunction. In this review, we will consider how inherent, age-related, depot-dependent alterations in preadipocyte function contribute to age-related fat tissue redistribution and metabolic dysfunction.

Fig. 1

Human preadipocyte capacity for lipid accumulation declines with age. Preadipocytes isolated from subcutaneous abdominal fat derived from healthy young (26 years, BMI: 27.6, male) and old subjects (79 years, BMI: 29.1, male), and passaged for four population doublings until confluency, were treated with differentiationinducing medium for 7 days.

Fig. 2

Potential depot-dependent differences in age-related changes in fat tissue distribution and function.

Fig. 3

Possible mechanisms of age-related mesenchymal progenitor dysfunction and ultimately fat redistribution and metabolic disease.