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NAD <sup>+</sup> repletion improves mitochondrial and stem cell function and enhances life span in mice

2016· article· en· 1,227 citations· W2343193821 on OpenAlex· 10.1126/science.aaf2693

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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-Dmd(mdx)/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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Science
Topic
Genetics, Aging, and Longevity in Model Organisms
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Funders
National Institute on AgingNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungUniversity of OttawaHeart and Stroke Foundation of Canada
Keywords
Life spanNAD+ kinaseStem cellMitochondrionFunction (biology)Cell biologyBiologyChemistryBiochemistryEvolutionary biologyEnzyme
Has abstract in OpenAlex
yes