Aging in adipocytes: potential impact of inherent, depot-specific mechanisms

Abstract

Fat mass and tissue distribution change dramatically throughout life. Fat depot sizes reach a peak by middle or early old age, followed by a substantial decline, together with fat tissue dysfunction and redistribution in advanced old age. These changes are associated with health complications, including type 2 diabetes, atherosclerosis, dyslipidemia, thermal dysregulation, and skin ulcers, particularly in advanced old age. Fat tissue growth occurs through increases in size and number of fat cells. Fat cells turn over throughout the lifespan, with new fat cells developing from preadipocytes, which are of mesenchymal origin. The pool of preadipocytes comprises 15-50% of the cells in fat tissue. Since fat tissue turns over throughout life, characteristics of these cells very likely have a significant impact on fat tissue growth, plasticity, function, and distribution. The aims of this review are to highlight recent findings regarding changes in preadipocyte cell dynamics and function with aging, and to consider how inherent characteristics of these cells potentially contribute to age- and depot-dependent changes in fat tissue development and function.

Figure 1. Diagram of age-associated changes in fat distribution

Fat mass reaches a peak by middle or early old age, followed by a substantial decline in advanced old age. Aging causes a loss of subcutaneous fat (peripherally first and then centrally), accumulation of visceral fat, and ectopic fat deposition (in muscle, liver, bone marrow, and elsewhere). White circles represent subcutaneous fat, red circles represent visceral fat, and yellow circles represent the appearance of fat in non adipose tissue.

Figure 2. Adipose tissue cell dynamics

Age-related changes in transcription factor function lead to reduced differentiation of preadipocytes.

Figure 3. Preadipocyte capacity for lipid accumulation declines with age

Differentiating preadipocytes isolated from young (3 month old), middle-aged (17 months), and old (24 months) Fischer 344 rat epididymal depots are shown.

Figure 4. Molecular mechanisms of age-related decreases in adipogenesis

Arrows and transcription factors in green indicate adipogenic pathways. Arrows and factors in red indicate antiadipogenic pathways. Age-related activation of cellular stress response pathways, coupled with increased preadipocyte cytokine generation, could trigger increased production of the antiadipogenic factors, C/EBPβ-LIP and CHOP. C/EBPβ-LIP and CHOP inhibit the production of the adipogenic transcription factors, PPARγ and C/EBPα, resulting in impaired adipogenesis and reduced expression of differentiation-dependent genes in fat cells. Reduced adipogenesis contributes to fat cell dysfunction, reduced fat depot size, and redistribution of fat to non-adipose tissues.