Ferro-aging: a potential driver of degenerative bone and joint diseases.
- 1First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- 2First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. [email protected].
- 3Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China. [email protected].
Abstract
Degenerative bone and joint diseases (DBJDs), including osteoporosis (OP), osteoarthritis (OA), and intervertebral disc degeneration (IVDD), are chronic age-related disorders characterized by progressive destruction of bone and joint tissues and loss of function, posing a heavy global health burden. Emerging evidence indicates that iron dyshomeostasis, chronic lipid peroxidation, and cellular senescence are common pathological features shared by these diseases. The newly discovered concept of ferro-aging-a non-lethal, persistent cellular state driven by sub-lethal lipid peroxidation that leads to cellular dysfunction and a senescence-associated secretory phenotype (SASP)-provides a unified mechanistic framework linking iron metabolism to age-related degeneration. This review systematically summarizes the molecular basis of ferro-aging, with a focus on the central role of ACSL4 in promoting membrane lipid remodeling and sustaining chronic lipid peroxidation. We discuss how ACSL4-associated ferro-aging contributes to the pathogenesis of OP, OA, and IVDD by disrupting local microenvironmental homeostasis, driving metabolic reprogramming, amplifying inflammatory SASP signaling, and impairing the function of key cell types such as osteoblasts (OBs), chondrocytes, and nucleus pulposus cells (NPCs). The differential response to the same ferro-aging program across different tissues determines the distinct clinical phenotypes of these diseases. Finally, we highlight potential intervention strategies targeting the ACSL4-ferro-aging axis and future research directions, offering new insights for the precision treatment of degenerative bone and joint diseases.
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BibTeX
@article{liang2026ferroaging,
title = {{Ferro-aging: a potential driver of degenerative bone and joint diseases.}},
author = {Songlin Liang and Shang Gao and Fumin Wang and Xintian Qu and Luming Kong and Chenmoji Wang and Nianhu Li},
journal = {Cell communication and signaling : CCS},
year = {2026},
month = sep,
doi = {10.1186/s12964-026-03194-3},
url = {https://europepmc.org/article/MED/42907920},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Ferro-aging: a potential driver of degenerative bone and joint diseases.
AU - Songlin Liang
AU - Shang Gao
AU - Fumin Wang
AU - Xintian Qu
AU - Luming Kong
AU - Chenmoji Wang
AU - Nianhu Li
PY - 2026
DA - 2026/09/01
JO - Cell communication and signaling : CCS
DO - 10.1186/s12964-026-03194-3
UR - https://europepmc.org/article/MED/42907920
AB - Degenerative bone and joint diseases (DBJDs), including osteoporosis (OP), osteoarthritis (OA), and intervertebral disc degeneration (IVDD), are chronic age-related disorders characterized by progressive destruction of bone and joint tissues and loss of function, posing a heavy global health burden. Emerging evidence indicates that iron dyshomeostasis, chronic lipid peroxidation, and cellular senescence are common pathological features shared by these diseases. The newly discovered concept of ferro-aging-a non-lethal, persistent cellular state driven by sub-lethal lipid peroxidation that leads to cellular dysfunction and a senescence-associated secretory phenotype (SASP)-provides a unified mechanistic framework linking iron metabolism to age-related degeneration. This review systematically summarizes the molecular basis of ferro-aging, with a focus on the central role of ACSL4 in promoting membrane lipid remodeling and sustaining chronic lipid peroxidation. We discuss how ACSL4-associated ferro-aging contributes to the pathogenesis of OP, OA, and IVDD by disrupting local microenvironmental homeostasis, driving metabolic reprogramming, amplifying inflammatory SASP signaling, and impairing the function of key cell types such as osteoblasts (OBs), chondrocytes, and nucleus pulposus cells (NPCs). The differential response to the same ferro-aging program across different tissues determines the distinct clinical phenotypes of these diseases. Finally, we highlight potential intervention strategies targeting the ACSL4-ferro-aging axis and future research directions, offering new insights for the precision treatment of degenerative bone and joint diseases.
SN - 1478-811X
ER -