Immunosenescence and bone remodeling: from immune cell senescence to skeletal aging through the bone marrow microenvironment
- 1Department of Orthodontics, Hospital of Stomatology, Jilin University
- 2Department of Oral Mucosal Diseases & Oral Emergency, Hospital of Stomatology, Jilin University
Abstract
With advancing age, the immune system undergoes progressive remodeling termed immunosenescence, which is intimately linked to skeletal homeostasis through the shared bone marrow microenvironment. This review systematically examines how senescent innate and adaptive immune cells disrupt bone remodeling by altering the cytokine milieu and releasing senescence-associated secretory phenotype (SASP) factors. Aged macrophages exhibit enhanced M1 proinflammatory polarization, while neutrophils display increased oxidative burst and delayed apoptosis. Natural killer cells lose cytotoxic capacity, and dendritic cells show impaired antigen presentation yet elevated basal inflammation. Within the adaptive compartment, T helper 17 (Th17) cells expand, regulatory T cells (Tregs) undergo functional decline and lineage instability, and B cells shift from osteoprotegerin (OPG) production toward receptor activator of nuclear factor kappa B ligand (RANKL) expression. These changes collectively elevate the RANKL/OPG ratio, promote osteoclastogenesis, and suppress osteoblast function. Systemic factors including estrogen deficiency and gut dysbiosis further amplify this immune-driven bone loss. Emerging therapeutic strategies range from conventional anti-resorptive agents to senolytics and immune modulators that restore marrow homeostasis. Understanding immunosenescence as an important contributor to skeletal aging provides a conceptual framework for immune-centered prevention and treatment of osteoporosis and fracture complications in the elderly, while recognizing that direct human causal evidence remains limited for several immune cell populations.
Related
- Inclisiran ameliorates diabetes-associated skeletal muscle remodeling through modulation of FOXO1/PDK4 and ER stress-UPR signaling
- TENASCIN-Dependent Mesenchymal–Epithelial Interactions Associated with Interstitial Microenvironment Remodeling in Cattle-Yak Lung: Insights from Single-Nucleus Transcriptomics
- 71 Spatial analysis of tumor microenvironment remodeling during non-small cell lung cancer progression
- The aging secretome as a candidate driver of bone remodeling imbalance: myokines, adipokines, and senescence-associated secretory factors
- Interferon-Associated Inflammatory Remodeling and Oxidative Metabolic Repression Define the Skeletal Muscle Transcriptomic Landscape of δ-Sarcoglycan Deficiency
BibTeX
@article{zhuang2026immunosenescence,
title = {{Immunosenescence and bone remodeling: from immune cell senescence to skeletal aging through the bone marrow microenvironment}},
author = {Jinliang Zhuang and Weiwei Yu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1979955},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1979955/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immunosenescence and bone remodeling: from immune cell senescence to skeletal aging through the bone marrow microenvironment
AU - Jinliang Zhuang
AU - Weiwei Yu
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1979955
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1979955/full
AB - With advancing age, the immune system undergoes progressive remodeling termed immunosenescence, which is intimately linked to skeletal homeostasis through the shared bone marrow microenvironment. This review systematically examines how senescent innate and adaptive immune cells disrupt bone remodeling by altering the cytokine milieu and releasing senescence-associated secretory phenotype (SASP) factors. Aged macrophages exhibit enhanced M1 proinflammatory polarization, while neutrophils display increased oxidative burst and delayed apoptosis. Natural killer cells lose cytotoxic capacity, and dendritic cells show impaired antigen presentation yet elevated basal inflammation. Within the adaptive compartment, T helper 17 (Th17) cells expand, regulatory T cells (Tregs) undergo functional decline and lineage instability, and B cells shift from osteoprotegerin (OPG) production toward receptor activator of nuclear factor kappa B ligand (RANKL) expression. These changes collectively elevate the RANKL/OPG ratio, promote osteoclastogenesis, and suppress osteoblast function. Systemic factors including estrogen deficiency and gut dysbiosis further amplify this immune-driven bone loss. Emerging therapeutic strategies range from conventional anti-resorptive agents to senolytics and immune modulators that restore marrow homeostasis. Understanding immunosenescence as an important contributor to skeletal aging provides a conceptual framework for immune-centered prevention and treatment of osteoporosis and fracture complications in the elderly, while recognizing that direct human causal evidence remains limited for several immune cell populations.
SN - 1664-3224
ER -