Research Article

NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice

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Science  17 Jun 2016:
Vol. 352, Issue 6292, pp. 1436-1443
DOI: 10.1126/science.aaf2693

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A dietary supplement protects aging muscle

The oxidized form of cellular nicotinamide adenine dinucleotide (NAD+) is critical for mitochondrial function, and its supplementation can lead to increased longevity. Zhang et al. found that feeding the NAD+ precursor nicotinamide riboside (NR) to aging mice protected them from muscle degeneration (see the Perspective by Guarente). NR treatment enhanced muscle function and also protected mice from the loss of muscle stem cells. The treatment was similarly protective of neural and melanocyte stem cells, which may have contributed to the extended life span of the NR-treated animals.

Science, this issue p. 1436; see also p. 1396

Abstract

Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD+) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD+ precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmdmdx/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD+ may reprogram dysfunctional SCs and improve life span in mammals.

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