Skin Chronological Aging Drives Age-related Bone Loss Via Secretion of Cystatin-A

Overview

Journal Nat Aging

Specialty Geriatrics

Date 2023 Apr 28

PMID 37118283

Authors

Wenquan Liang

Qingjing Chen

Shasha Cheng

Ruiming Wei

Yuejun Li

Chenfeng Yao

Zhicong Ouyang

Dawei Kang

Ajuan Chen

Zezheng Liu

Kai Li

Xiaochun Bai

Qingchu Li

Bin Huang

Affiliations

Soon will be listed here.

Abstract

Although clinical evidence has indicated an association between skin atrophy and bone loss during aging, their causal relationship and the underlying mechanisms are unknown. Here we show that premature skin aging drives bone loss in mice. We further identify that cystatin-A (Csta), a keratinocyte-enriched secreted factor, mediates the effect of skin on bone. Keratinocyte-derived Csta binds the receptor for activated C-kinase 1 in osteoblast and osteoclast progenitors, thus promoting their proliferation but inhibiting osteoclast differentiation. Csta secretion decreases with skin aging in both mice and humans, thereby causing senile osteoporosis by differentially decreasing the numbers of osteoblasts and osteoclasts. In contrast, topical application of calcipotriol stimulates Csta production in the epidermis and alleviates osteoporosis. These results reveal a mode of endocrine regulation of bone metabolism in the skin, and identify Csta as an epidermally derived hormone linking skin aging to age-related bone loss. Enhancers of skin Csta levels could serve as a potential topical drug for treatment of senile osteoporosis.

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