The aging secretome as a candidate driver of bone remodeling imbalance: myokines, adipokines, and senescence-associated secretory factors
- 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Abstract
Bone homeostasis depends on the spatial and temporal coupling of osteoclastic resorption to osteoblastic formation. With aging, this balance shifts toward net bone loss alongside sarcopenia, marrow adipose expansion, and chronic low-grade inflammation. These parallel changes may be linked by a shared set of secreted signals, termed here the aging secretome. We distinguish functional remodeling imbalance, defined as a sustained shift between formation and resorption, from direct uncoupling, in which a resorption-to-formation coupling signal is demonstrably disrupted. The aging secretome comprises three principal arms: muscle-derived signals, including myostatin, irisin, and myogenic extracellular vesicles; fat-derived signals, including leptin, adiponectin, and marrow adipocyte lipotoxicity; and senescence-associated secretory factors, particularly those involving senescent osteocytes, TNF-α, and IL-6. Inflammaging is treated as a shared contextual amplifier rather than a separate signaling arm. These pathways converge on key regulators of skeletal remodeling, including RANKL, Wnt–sclerostin, and IGF-1. This framework also provides a common context for comparing pathway-specific interventions, such as activin type II receptor blockade and sclerostin inhibition, with broader approaches targeting senescence or inflammation. An early phase 2 senolytic trial was negative overall, with only an exploratory signal in women with high senescent-cell burden. The aging secretome should therefore be viewed as an organizing framework whose individual pathways and relative contributions require further validation in human bone.
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BibTeX
@article{fang2026aging,
title = {{The aging secretome as a candidate driver of bone remodeling imbalance: myokines, adipokines, and senescence-associated secretory factors}},
author = {Hanhong Fang and Xianglong Zhou and Yang Liu and Weicheng Chen and Fulin Zhou and Haoran Zhou and Jianhui Xiang and Liming Xiong},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1982491},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1982491/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The aging secretome as a candidate driver of bone remodeling imbalance: myokines, adipokines, and senescence-associated secretory factors
AU - Hanhong Fang
AU - Xianglong Zhou
AU - Yang Liu
AU - Weicheng Chen
AU - Fulin Zhou
AU - Haoran Zhou
AU - Jianhui Xiang
AU - Liming Xiong
PY - 2026
DA - 2026/10/26
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1982491
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1982491/full
AB - Bone homeostasis depends on the spatial and temporal coupling of osteoclastic resorption to osteoblastic formation. With aging, this balance shifts toward net bone loss alongside sarcopenia, marrow adipose expansion, and chronic low-grade inflammation. These parallel changes may be linked by a shared set of secreted signals, termed here the aging secretome. We distinguish functional remodeling imbalance, defined as a sustained shift between formation and resorption, from direct uncoupling, in which a resorption-to-formation coupling signal is demonstrably disrupted. The aging secretome comprises three principal arms: muscle-derived signals, including myostatin, irisin, and myogenic extracellular vesicles; fat-derived signals, including leptin, adiponectin, and marrow adipocyte lipotoxicity; and senescence-associated secretory factors, particularly those involving senescent osteocytes, TNF-α, and IL-6. Inflammaging is treated as a shared contextual amplifier rather than a separate signaling arm. These pathways converge on key regulators of skeletal remodeling, including RANKL, Wnt–sclerostin, and IGF-1. This framework also provides a common context for comparing pathway-specific interventions, such as activin type II receptor blockade and sclerostin inhibition, with broader approaches targeting senescence or inflammation. An early phase 2 senolytic trial was negative overall, with only an exploratory signal in women with high senescent-cell burden. The aging secretome should therefore be viewed as an organizing framework whose individual pathways and relative contributions require further validation in human bone.
SN - 1664-2392
ER -