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Despite the increasing average age of individuals with multiple sclerosis (MS), little is known about what happens to the immune system of aging people with MS or about the impact of immunomodulatory and immunosuppressive treatments for MS on the aging immune system. In this topical review, we discuss the concepts of physiological cellular senescence and immunosenescence, and we review the latest available data on immunosenescence in MS. We examine evidence suggesting premature aging of the immune system in MS, including premature aging of T cells, reduced numbers of na\u00efve lymphocytes, expansion of proinflammatory CD28\u2212 T cells, and the acquisition of an \u201caged\u201d phenotype of CD8+ T cells in younger MS patients. 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