Defective cholesterol clearance limits remyelination in the aged central nervous system

Keeping cholesterol at bay A decline in tissue repair is a universal hallmark of aging. The failure to regenerate myelin sheaths in multiple sclerosis lesions contributes to chronic progressive disease and disability. Understanding the cause and preventing this failure is a key goal in regenerative medicine. Cantuti-Castelvetri et al. report that the self-limiting inflammatory response, which is necessary for remyelination to occur, is maladaptive in the central nervous system (CNS) of old mice (see the Perspective by Chen and Popko). Cholesterol-rich myelin debris overwhelmed the efflux capacity of phagocytes, resulting in a transition of free cholesterol into crystals, thereby inducing lysosomal rupture and inflammasome stimulation. Thus, drugs being developed to promote cholesterol clearance in human atherosclerosis lesions may also be good candidates for regenerative medicine in the CNS. Science , this issue p. 684 ; see also p. 635