The Bidirectional Role of Obesity and Aging in the Pathogenesis of Osteoarthritis: Molecular Mechanisms, Epigenetic Insights, and Therapeutic Implications.

Osteoarthritis (OA) is a major global contributor to pain, disability, and socioeconomic burden. With the increasing prevalence of obesity and an aging population, the incidence of OA continues to rise. This review explores the bidirectional relationship between obesity and aging in the pathogenesis of OA, focusing on the underlying molecular mechanisms. Obesity contributes to aging by inducing oxidative stress, chronic inflammation, and metabolic dysregulation, thereby promoting OA development and progression. Conversely, the accumulation of senescent cells with age exacerbates obesity-induced inflammation and metabolic dysfunction by secreting pro-inflammatory cytokines and bioactive molecules. Epigenetic changes, including DNA methylation, histone modifications, and the regulation of non-coding RNAs, play pivotal roles in modulating these interactions, further influencing OA progression. The review also discusses current and emerging therapeutic strategies targeting the obesity-aging-OA axis, highlighting the potential of epigenetic interventions and novel anti-inflammatory treatments. A comprehensive understanding of the molecular interplay between obesity and aging in OA is essential for developing more effective prevention and treatment strategies. Future research should prioritize the in-depth exploration of epigenetic mechanisms, coupled with technological innovation, standardized education and training, quality control, and multidisciplinary collaboration. Targeted strategies and interventions are essential to effectively prevent and manage obesity- and OA-related diseases.