When the Brain Grows Old Too Soon: Aging and Senescence As a Driver of MS Progression

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. While onset usually occurs in young adulthood, older age worsens MS prognosis with accelerated accumulation of disability and higher susceptibility to the progressive form of MS, characterized by continuous symptoms without periods of remission. Treatment responsiveness also declines with age, changing the landscape of available therapies for older patients. Recent work has begun to uncover an accelerated aging and senescence-like phenotype arising in patients with MS and its preclinical animal models. This review explores the current evidence for inflammatory injury driving age-related changes in brain cells in patients with MS and preclinical animal models, its interactions with sex and hormones, and the possible future for anti-aging therapeutic strategies to address this evolving neurodegenerative phenotype of MS during aging.