Aging is associated with profound changes in cellular function (senescence) and affects various tissues and systems, including the immune system (immunosenescence). 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 naïve lymphocytes, expansion of proinflammatory CD28− T cells, and the acquisition of an “aged” phenotype of CD8+ T cells in younger MS patients. Finally, we explore the clinical implications of immunosenescence on the efficacy and safety of disease-modifying therapies and propose drug candidates that could be tested in aged MS patients.
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