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Musculoskeletal pain is a common problem in the general population and in persons with spinal cord injury (SCI). Aging has significant impacts on the musculoskeletal system. The interaction of aging and musculoskeletal demands in persons with spinal cord injury (SCI) results in unique problems that interfere with functional independence and quality of life. An understanding of these effects is needed to better design strategies and programs for primary prevention of musculoskeletal conditions that interfere with the lives of persons with SCI. This review summarizes some of these age-related changes and methods used to minimize their impact.