The Impact of Aging on Adipose Function and Adipokine Synthesis

Abstract

During the last 40 years, there has been a world-wide increase in both the prevalence of obesity and an increase in the number of persons over the age of 60 due to a decline in deaths from infectious disease and the nutrition transition in low and middle income nations. While the increase in the elderly population indicates improvements in global public health, this population may experience a diminished quality of life due to the negative impacts of obesity on age-associated inflammation. Aging alters adipose tissue composition and function resulting in insulin resistance and ectopic lipid storage. A reduction in brown adipose tissue activity, declining sex hormones levels, and abdominal adipose tissue expansion occur with advancing years through the redistribution of lipids from the subcutaneous to the visceral fat compartment. These changes in adipose tissue function and distribution influence the secretion of adipose tissue derived hormones, or adipokines, that promote a chronic state of low-grade systemic inflammation. Ultimately, obesity accelerates aging by enhancing inflammation and increasing the risk of age-associated diseases. The focus of this review is the impact of aging on adipose tissue distribution and function and how these effects influence the elaboration of pro and anti-inflammatory adipokines.

Keywords: adipokines; adipose tissue; aging; cardiovascular disease; diabetes; menopause.

Figure 1

Aging promotes the redistribution of lipids from the subcutaneous to the abdominal visceral compartment. Aging promotes cellular senescence and impairs mesenchymal stem cell (MSC) differentiation in subcutaneous adipose tissue. These changes diminish adipocyte function by reducing preadipocyte maturation, restrict adipocyte hyperplasia, and reduce subcutaneous adipocyte mass. In addition, declining sex hormones in men (testosterone) and women (estrogen) also contribute to visceral adipose tissue expansion. Brown adipose tissue declines because of reduced sympathetic output and increases in the transcription factor FOXOA3. Subsequently, lipids are redistributed to the abdominal adipose tissue depot. As adipose tissue expands in this compartment, adipocytes undergo hypertrophy, a process that contributes to adipocyte necrosis, adipose tissue inflammation, and the elaboration of proinflammatory classical cytokines and adipokines. Monocytes and other immune cells are recruited to the visceral adipose tissue depot to remove necrotic adipocytes and participate in tissue remodeling limiting lipid storage. Ultimately, these events contribute to ectopic lipid storage and insulin resistance. Bone marrow adipose tissue expands to replace hematopoietic cells and this is associated with increased adiponectin synthesis. While many pro and anti-inflammatory adipokines increase with age, the dominance of proinflammatory adipokines shifts the balance to favor a chronic state of inflammation.