Aging is characterized by a progressive decline in physiological resilience and functional capacity, often accompanied by chronic, low-grade systemic inflammation, a phenomenon termed "inflammaging". This persistent inflammatory milieu contributes significantly to musculoskeletal degeneration, impaired neuromotor coordination, and reduced mobility, collectively diminishing quality of life, particularly among older adults. Key biological drivers of inflammaging include cellular senescence, immune system dysregulation, and mitochondrial dysfunction, which are orchestrated through complex molecular signaling pathways such as NF-κB, mTOR, JAK/STAT, MAPK, and NLRP3. These pathways facilitate the development of the senescence-associated secretory phenotype (SASP), thereby perpetuating tissue damage and systemic inflammation. Mobility decline, frequently manifesting as sarcopenia, osteoarthritis (OA), and gait instability, is closely associated with these inflammatory processes. Early identification of individuals at risk for mobility decline using biomarkers and functional assessments enables timely and targeted interventions that can help extend 'mobility span'. Foundational strategies such as lifestyle modification remain critical in mitigating the effects of inflammaging however, emerging therapeutic modalities including nutraceuticals and pharmacological agents offer promising avenues for intervention. This review synthesizes current evidence on the interplay between inflammaging and mobility decline, emphasizing mechanistic insights, therapeutic approaches, and future research directions. Addressing these interconnected biological processes is essential for promoting healthy aging, preserving functional independence, and extending health span.
