Aging and Multiple Sclerosis

ABSTRACT Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. While typically diagnosed in young adults, late‐onset MS (LOMS, onset > 50 years) is becoming increasingly recognized, presenting with distinct features such as higher rates of progressive onset and motor symptoms. With prolonged life expectancy and widespread use of disease‐modifying therapies (DMTs), the population of aging individuals with MS is growing. Managing DMTs in this population is challenging, requiring the balancing of decreased relapse frequency against increased comorbidity and treatment risks. Discontinuation decisions are complex, as disease activity, including progression‐independent of relapse activity (PIRA), can persist. Research, including ongoing trials, is evaluating the role of DMTs in preventing progression in older patients. Furthermore, aging involves biological processes such as immunosenescence, inflammaging (driven by cells with a senescence‐associated secretory phenotype), and structural central nervous system changes such as enlarged perivascular spaces. These age‐related alterations in immune and neurodegenerative pathways show significant overlap with MS pathophysiology. Understanding this intersection is crucial for optimizing clinical management in older MS patients and may identify novel targets for disease modification.