Beyond chronological age: biological aging and its relevance for motor and cognitive function in multiple sclerosis

The aging of the global population has profound implications for multiple sclerosis (MS), a disease increasingly affecting older adults. Motor and cognitive impairments are common in both aging and MS, strongly predicting fall risk, independence, and quality of life. Yet chronological age, the most common clinical proxy, does not capture how disease-specific pathology and biological processes shape these outcomes. This review evaluates biological aging as a framework for understanding how motor and cognitive trajectories in MS diverge from typical aging. Evidence from telomere length, epigenetic clocks, cellular senescence, reproductive aging, and neuroimaging-derived brain age was synthesized. A targeted literature search of PubMed and related databases was conducted to identify relevant studies on biological aging in MS, with emphasis on motor and cognitive outcomes. Outcomes indicate accelerated biological aging in MS, with brain-predicted age showing the strongest functional associations, linking older-appearing brains to slower gait, greater disability, and reduced processing speed. Integrating biological-age frameworks could enable earlier detection of decline, guide targeted interventions, and improve quality of life in older adults with MS.