Osteolineage cells ablation promotes skin aging phenotypes via dysregulated bone marrow macrophages

Sen-Yao Zhang1,2, Zhi-Kai Zheng1,2, Fang Ye3,4

  • 1Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.

Iscience
|March 9, 2026
PubMed

Insights

Bone loss accelerates skin aging by affecting bone marrow macrophages, which then impact skin health. This study reveals a new skeletal-immune-skin axis influencing aging.

Area of Science:

  • Gerontology
  • Dermatology
  • Immunology

Background:

  • Clinical observations link bone loss to skin thinning in aging.
  • The specific role of bone in regulating skin aging remains largely unknown.

Purpose of the Study:

  • To investigate the causal relationship between bone health and skin aging.
  • To elucidate the mechanisms by which bone influences skin aging.

Main Methods:

  • Partial ablation of osteolineage cells in a model system.
  • Single-cell RNA sequencing of bone marrow and skin.
  • Analysis of skin aging markers, wound healing, and hair regeneration.
  • Integration with existing skin aging datasets.

Main Results:

  • Osteolineage cell ablation induced skin aging phenotypes, including dermal thinning and impaired regeneration.
  • Bone marrow macrophages exhibited pro-inflammatory activation, metabolic issues, and enhanced SASP signaling.
  • Dysfunctional macrophages infiltrated the skin, causing aging-like changes in skin cells and inflammation.
  • These changes mirrored key molecular features of natural skin aging.

Conclusions:

  • Bone plays a critical role in regulating skin aging through a skeletal-immune-skin axis.
  • Bone marrow macrophage dysfunction is a key mediator linking bone health to skin aging.
  • Maintaining bone homeostasis may be crucial for preventing or mitigating skin aging.
Keywords:
Immunology

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