Fig. 5.

Model of the pathological observations in aged muscle and their reversal by augmentation of nuclear and mitochondrial NAD+ levels. a Fewer mitochondria, fewer muscle stem cells, reduced levels of NAD+ in nuclei and mitochondria, and reduced nuclear SIRT-1 activity have been observed in aged muscle. b Repletion of NAD+ levels in nuclei and mitochondria via various interventions increases mitochondria, increases muscle stem cells, and increases nuclear and mitochondrial NAD+ levels thereby increasing SIRT-1 activity. One mechanism involves nuclear SIRT-1-mediated regulation of TFAM and PGC1alpha gene expression and their effect on mitochondrial metabolism