HOXC10 Protects from Skin Aging by Targeting the FZD6/Wnt/β-Catenin Signaling Pathway

TL;DR

This study shows that HOXC10 delays skin aging by regulating the Wnt/β-catenin pathway and suggests simvastatin as a potential treatment.

Contribution

HOXC10 is identified as a novel regulator of skin aging through the FZD6/Wnt/β-catenin pathway, with simvastatin proposed as a functional mimic.

Findings

HOXC10 expression is reduced in aging skin and senescent fibroblasts.

HOXC10 activates the Wnt/β-catenin pathway by targeting FZD6, delaying aging.

Simvastatin mimics HOXC10's anti-aging effects in vitro and in vivo.

Abstract

Aging, caused by a variety of exogenous stimuli and internal factors, leads to a gradual and irreversible decline in the function of the organism. The aging process involves complex gene regulation, in which transcription factors may play a key role as core regulatory elements. In this study, the single-cell transcriptome of skin revealed homeobox C10 (HOXC10) as a core element in the transcription factor regulatory network associated with skin aging. In vivo and vitro, the expression of HOXC10 was down-regulated in senescent fibroblasts and aging tissues, and overexpressed HOXC10 delayed cell senescence and skin aging. Mechanistically, HOXC10 targeted the promoter region of frizzled 6 (FZD6) to reduce its expression and therefore activated the Wnt/β-catenin signaling pathway to delay aging. Finally, by using the Connectivity Map approach, we explored simvastatin as a functional mimic of HOXC10 and demonstrated its antiaging ability in vitro and vivo. In conclusion, our results establish the role of HOXC10/FZD6/Wnt signals in skin aging and identify simvastatin as a potential therapeutic strategy to delay aging.

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