Ageing research reviewsJul 6, 2026

Aging of Bone Stem Cells: Causes, Effects on Bone Aging, and Possible Treatments

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 7, 2026

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) undergo profound functional deterioration during aging.

Aging skeletons are linked to disorders like osteoporosis and osteoarthritis.
BMSCs experience impaired proliferation and differentiation as they age.
Epigenetic changes, including DNA methylation and histone modifications, are associated with BMSC aging.
Senescent BMSCs adopt a pro-inflammatory state known as the senescence-associated secretory phenotype (SASP).
The interaction between senescent BMSCs and the bone microenvironment contributes to age-related bone diseases.
Future research may explore multi-omics, single-cell technologies, and targeted epigenetic interventions.

Simplified

Aging of the skeleton is a hallmark of organismal decline and underlies prevalent age-related disorders such as osteoporosis and osteoarthritis. Bone marrow-derived mesenchymal stem cells (BMSCs), the primary source of osteoblasts, undergo profound functional deterioration during senescence, leading to an imbalance between bone formation and resorption. This review systematically summarizes the key features of BMSC senescence, including impaired proliferation and differentiation, epigenetic dysregulation, and the acquisition of a pro-inflammatory senescence-associated secretory phenotype (SASP). We highlight recent advances in understanding how epigenetic mechanisms (DNA methylation, histone modifications, RNA methylation, and non-coding RNAs) orchestrate BMSC aging. In addition, we discuss the intricate crosstalk between senescent BMSCs and the bone microenvironment, emphasizing their contribution to age-related bone diseases. Finally, we propose future research directions, including the integration of multi‑omics, single-cell technologies, and targeted epigenetic interventions, as well as emerging therapeutic strategies such as senolytics, metabolic modulators, and extracellular vesicle-based approaches. A deeper understanding of BMSC aging will facilitate the development of novel treatments to preserve bone health and combat aging-related skeletal disorders.

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Competing interests

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of Competing Interest The authors have declared that no competing interest exists.

PubMed

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Aging of Bone Stem Cells: Causes, Effects on Bone Aging, and Possible Treatments

Abstract

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Competing interests

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