Musculoskeletal degeneration and cardiovascular aging: a narrative review of shared mechanobiological pathways

Aging is characterized by progressive changes in several organ systems, which specifically affects the musculoskeletal and cardiovascular system. Traditionally, recent discoveries have highlighted common mechanical pathways that combine musculoskeletal degeneration with cardiovascular aging. Understanding these mechanisms can provide new insights into integrated prevention and treatment strategies. This narrative overview integrates current evidence of age-related structural and functional changes in the musculoskeletal and cardiovascular system, highlighting mechanical pathways such as YAP/TAZ, Wnt/β-catenin, TGF-β, and integrin signaling. Clinical studies co-degeneration, common risk factors, and testing therapeutic interventions have been critically analyzed to highlight the meaning of translation. Musculoskeletal degeneration manifests as sarcopenia, osteoporosis and arthritis, whereas cardiovascular aging is characterized by vascular sclerosis, myocardial fibrosis, dysfunction of endothelium. Both systems share common mechanisms including low degrees' inflammation, oxidative stress, mitochondrial dysfunction, and impaired chronic inflammation with dysregulated extracellular matrix remodeling, and disorders of chronic inflammation. Clinical evidence shows that musculoskeletal waste promotes cardiovascular degradation and vice versa, contributing to frailty, reduced mobility and increased mortality. Important common risk factors, sedentary lifestyle, metabolic disorders, oxidative stress, and hormonal changes, promote parallel degeneration. Lifestyle changes, targeted drugs, optimized nutrition, and regenerative medicine offer potential to reduce co-degeneration. Connected biological and mechanical pathways link musculoskeletal and cardiovascular aging that requires integrated diagnosis and treatment. Targeting mechanical dysfunction and systemic risk factors can improve resistance and quality of life in older adult. Future research should focus on longitudinal studies, biomarker identification, and personalized interventions to promote healthy aging through interconnected systems.