Subcutaneous adipose tissue (SAT) is a type of white adipose tissue beneath the skin, and involves in energy storage, thermal insulation, mechanical protection and endocrine. During natural aging, SAT gradually diminishes and may even be completely lost; this not only causes skin sagging and deepening wrinkles on the face and limbs, affecting appearance, but also compromises wound healing and endocrine. In Hutchinson-Gilford progeria syndrome (HGPS), a rare progeroid disorder caused by progerin, SAT loss is also one of the prominent symptoms. However, the mechanism underlying the aging-associated SAT loss remains largely unclear.
Recent research, led by Professor Chuanmao Zhang and colleagues, revealed that vitamin D receptor (VDR) signaling plays a vital role in maintaining SAT homeostasis, and VDR deficiency drives SAT loss during aging. Importantly, vitamin D supplement reverses VDR deficiency and SAT loss in HGPS, providing a new target and strategy for skin aging intervention.
The researchers found that, in both natural aging and HGPS, SAT decline is attributed to fewer adipocytes rather than smaller adipocyte size. RNA sequencing and in vitro adipogenesis showed that adipogenesis defect contributes to SAT loss in natural aging and HGPS. Further study demonstrated that VDR signaling enables adipogenesis by upregulating commitment factor ZNF423 and adipogenesis activators while downregulating adipogenesis inhibitors, and VDR deficiency drives subcutaneous adipogenesis defect and SAT decline in both natural aging and HGPS mice.
More importantly, the researchers found that SAT loss could be reversed. Supplementation with the VDR agonist calcipotriol counteracted VDR deficiency, rescued SAT loss, and even extended the lifespan of HGPS mice.
These findings strongly suggest that vitamin D supplement could be a powerful therapeutic strategy for SAT loss in both natural aging and HGPS. By reversing SAT loss, scientists are hopeful that new treatments can be developed to combat skin aging and preserve a youthful appearance. This research highlights the pivotal role of VDR signaling in SAT maintenance, and opens exciting possibilities for skin aging intervention.
DOI:10.1093/procel/pwag045