Proteomics

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Mouse stem cell SWATH-MS

ABSTRACT: Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to SC senescence during aging. Here we demonstrate the importance of cellular NAD+ level and its impact on mitochondrial activity as a pivotal switch to modulate muscle stem cell (MuSC) senescence. Importantly, the induction of the mitochondrial unfolded protein response (UPRmt) and of prohibitin proteins, subsequent to increasing cellular NAD+ with the precursor nicotinamide riboside (NR), rejuvenates MuSCs in aged mice. NR also prevents MuSCs senescence in Mdx mice, a mouse model of muscular dystrophy. Extending these observations to other SC pools and on the organism as a whole, we demonstrate that NR delays neural stem cell (NSC) and melanocyte stem cell (McSC) senescence, while also increasing mouse lifespan. Strategies that conserve cellular NAD+ could therefore be utilized to reprogram dysfunctional SCs in aging and disease to improve lifespan in mammals

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Stem Cell, Muscle

SUBMITTER: Yibo Wu  

LAB HEAD: Ruedi Aebersold

PROVIDER: PXD003865 | Pride | 2022-02-22

REPOSITORIES: Pride

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Publications

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

Zhang Hongbo H   Ryu Dongryeol D   Wu Yibo Y   Gariani Karim K   Wang Xu X   Luan Peiling P   D'Amico Davide D   Ropelle Eduardo R ER   Lutolf Matthias P MP   Aebersold Ruedi R   Schoonjans Kristina K   Menzies Keir J KJ   Auwerx Johan J  

Science (New York, N.Y.) 20160428 6292

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,  ...[more]

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