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Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells

Author

Listed:
  • Xuan Sun

    (Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
    Monash University)

  • Benjamin Cao

    (Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
    Monash University)

  • Marina Naval-Sanchez

    (The University of Queensland)

  • Tony Pham

    (The University of Queensland)

  • Yu Bo Yang Sun

    (Monash University
    Monash Biomedicine Discovery Institute
    Monash University)

  • Brenda Williams

    (Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
    Monash University)

  • Shen Y. Heazlewood

    (Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
    Monash University)

  • Nikita Deshpande

    (The University of Queensland)

  • Jinhua Li

    (Monash Biomedicine Discovery Institute
    Monash University)

  • Felix Kraus

    (Monash Biomedicine Discovery Institute
    Monash University)

  • James Rae

    (The University of Queensland)

  • Quan Nguyen

    (The University of Queensland)

  • Hamed Yari

    (The University of Queensland)

  • Jan Schröder

    (Monash University
    Monash Biomedicine Discovery Institute
    Monash University)

  • Chad K. Heazlewood

    (Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
    Monash University)

  • Madeline Fulton

    (Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
    Monash University)

  • Jessica Hatwell-Humble

    (Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
    Monash University)

  • Kaustav Gupta

    (The University of Queensland
    The University of Queensland
    The University of Queensland)

  • Ronan Kapetanovic

    (The University of Queensland
    The University of Queensland
    The University of Queensland)

  • Xiaoli Chen

    (The University of Queensland)

  • Matthew J. Sweet

    (The University of Queensland
    The University of Queensland
    The University of Queensland)

  • Robert G. Parton

    (The University of Queensland
    The University of Queensland)

  • Michael T. Ryan

    (Monash Biomedicine Discovery Institute
    Monash University)

  • Jose M. Polo

    (Monash University
    Monash Biomedicine Discovery Institute
    Monash University)

  • Christian M. Nefzger

    (Monash University
    The University of Queensland
    Monash Biomedicine Discovery Institute
    Monash University)

  • Susan K. Nilsson

    (Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
    Monash University)

Abstract

With age, hematopoietic stem cells (HSC) undergo changes in function, including reduced regenerative potential and loss of quiescence, which is accompanied by a significant expansion of the stem cell pool that can lead to haematological disorders. Elevated metabolic activity has been implicated in driving the HSC ageing phenotype. Here we show that nicotinamide riboside (NR), a form of vitamin B3, restores youthful metabolic capacity by modifying mitochondrial function in multiple ways including reduced expression of nuclear encoded metabolic pathway genes, damping of mitochondrial stress and a decrease in mitochondrial mass and network-size. Metabolic restoration is dependent on continuous NR supplementation and accompanied by a shift of the aged transcriptome towards the young HSC state, more youthful bone marrow cellular composition and an improved regenerative capacity in a transplant setting. Consequently, NR administration could support healthy ageing by re-establishing a more youthful hematopoietic system.

Suggested Citation

  • Xuan Sun & Benjamin Cao & Marina Naval-Sanchez & Tony Pham & Yu Bo Yang Sun & Brenda Williams & Shen Y. Heazlewood & Nikita Deshpande & Jinhua Li & Felix Kraus & James Rae & Quan Nguyen & Hamed Yari &, 2021. "Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22863-0
    DOI: 10.1038/s41467-021-22863-0
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