Skin aging: are adipocytes the next target?

Abstract

Dermal white adipose tissue (dWAT) is increasingly appreciated as a special fat depot. The adipocytes in this depot exert a variety of unique effects on their surrounding cells and can undergo massive phenotypic changes. Significant modulation of dWAT content can be observed both in intrinsically and extrinsically aged skin. Specifically, skin that has been chronically photo-damaged displays a reduction of the dWAT volume, caused by the replacement of adipocytes by fibrotic structures. This is likely to be caused by the recently uncovered process described as "adipocyte-myofibroblast transition" (AMT). In addition, contributions of dermal adipocytes to the skin aging processes are also indirectly supported by spatial correlations between the prevalence of hypertrophic scarring and the appearance of signs of skin aging in different ethnic groups. These observations could elevate dermal adipocytes to prime targets in strategies aimed at counteracting skin aging.

Keywords: adipocyte-myofibroblast transition; dermal adipocytes; skin aging; ultraviolet radiation.

Figure 1. Typical layered dWAT structures in rodents and humans

(A) Section of the dWAT from the C57/BI6 mouse. This dWAT depot has the layered form placed parallel to the panniculus carnosus. (B) Human dermal adipocytes in the form of “dermal cones” around the pilosebaceous units. Single “dermal cones” can protrude into the upper dermis. These dermal cones are connected on the other end with sWAT. Pictures courtesy of Drs. Min Kim (A) and Travis Vandergriff (4), UT Southwestern Medical Center and published in [32].

Figure 2. Possible role of adipocyte-myofibroblast transition in extrinsic aging

Absorption of UV radiation in the skin causes acute enlargement of the dWAT layer. However, upon chronic overexposure to UV radiation, it causes the depletion of dWAT and a concurrent development of cutaneous fibrosis, presumably through adipocyte-myofibroblast transition (AMT). Replacement of dWAT volume with fibrosis leads to production of mechanically heterogeneous skin structures and to the loss of the effective skin volume.