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Osteoimmune senescence in aging-related bone diseases
Huali Li1, Yingli Yang2, Huanle Zhu1
1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Frontiers in Immunology
|July 30, 2026
Summary
Aging bone diseases involve complex immune-skeletal interactions. Osteoimmune senescence, driven by senescent cells and immune changes, contributes to reduced bone strength and impaired healing across various conditions.
Area of Science:
- Gerontology
- Immunology
- Orthopedics
- Skeletal Biology
Background:
- Aging-related bone diseases are characterized by disrupted bone remodeling influenced by immune system changes.
- Osteoimmune senescence is an emerging framework linking cellular senescence, immune dysregulation, and bone health decline.
Purpose of the Study:
- To review and consolidate evidence on osteoimmune senescence in aging-related bone diseases.
- To explore the shared and distinct mechanisms of senescence in conditions like osteoporosis, arthritis, and fracture healing.
Main Methods:
- Literature review of current evidence on cellular senescence, immune-skeletal interactions, and bone diseases.
- Analysis of the roles of senescent skeletal cells and aging immune cells in bone remodeling.
- Discussion of imaging and metabolite readouts relevant to osteoimmune senescence.
Main Results:
- Senescent cells in bone (osteocytes, osteoblasts, stromal cells) disrupt bone remodeling by altering RANKL/OPG balance and suppressing osteogenesis.
- Aging immune cells (T cells, macrophages, neutrophils, NK cells) modulate osteoclastogenesis and impair fracture healing.
- Shared osteoimmune senescence mechanisms may underlie distinct bone diseases, with disease-specific endotypes.
Conclusions:
- Osteoimmune senescence is a unifying concept for aging bone diseases, involving senescent cells, immune changes, and niche deterioration.
- Therapeutic strategies targeting senescent cells, immune recalibration, and microbiota may offer new treatments for bone diseases.
- Matching interventions to disease stage and cellular targets is crucial for effective therapeutic translation.
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