Running on empty: Exploring stem cell exhaustion in geriatric musculoskeletal disease

• Published in: Maturitas 2024-10, Vol.188, p.108066, Article 108066
• Main Authors: Lawton, Amy, Tripodi, Nicholas, Feehan, Jack
• Format: Article
• Language: English
• Subjects: Ageing; Geroscience; Mesenchymal stem cells; Musculoskeletal disease; Osteoporosis; Sarcopenia; Satellite cells; Stem cell exhaustion
• ISSN: 0378-5122; 1873-4111; 1873-4111
• DOI: 10.1016/j.maturitas.2024.108066

•Stem cell exhaustion is a promising avenue for regenerative therapies in musculoskeletal disease in ageing.•Mechanisms underpinning stem cell exhaustion are unclear.•Senescence of mesenchymal progenitors in bone marrow and muscle leads to decreased proliferation.•There is a shift away from myo- and osteogenesis, toward adipogenesis in both muscle and bone.•Questions remain as to whether these are a primary stem effect, or a systemic change in the niche microenvironment. Ageing populations globally are associated with increased musculoskeletal disease, including osteoporosis and sarcopenia. These conditions place a significant burden of disease on the individual, society and the economy. To address this, we need to understand the underpinning biological changes, including stem cell exhaustion, which plays a key role in the ageing of the musculoskeletal system. This review of the recent evidence provides an overview of the associated biological processes. The review utilised the PubMed/Medline, Science Direct, and Google Scholar databases. Mechanisms of ageing identified involve a reaction to the chronic inflammation and oxidative stress associated with ageing, resulting in progenitor cell senescence and adipogenic differentiation, leading to decreased mass and quality of both bone and muscle tissue. Although the mechanisms underpinning stem cell exhaustion are unclear, it remains a promising avenue through which to identify new strategies for prevention, detection and management.