Restoration of NAD+ via inhibition of CD38 improves aging-induced decline in muscle stem cells functions and muscle regeneration

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Previous reports show macrophages-derived signals are crucial for regeneration process. Both macrophages and satellite cells require nicotinamide adenine dinucleotide (NAD+) for their biological functions. Aging-related decline in NAD+ is reported to impair regenerative process and significantly inhibits satellite cells differentiation. Administration of NAD+ precursors restore NAD+ deficiency in aged muscle and also enhances recovery process. CD38 is an ectoenzyme to degrade NAD+ and is reportedly increased in inflammatory macrophages during aging. However, how inhibition of CD38 affects satellite cells functions in aging-induced delay in recovery process, remain elusive. We are currently investigating how deletion of CD38 in aged mice affect regenerative capacity of muscle stem cells. Our initial results reveal that blocking/inhibition of CD38 results in restoration of NAD+ and muscle stem cell functions.