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

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, Jan Schröder, Chad K. Heazlewood, Madeline Fulton, Jessica Hatwell-Humble, Kaustav Gupta, Ronan Kapetanovic, Xiaoli Chen, Matthew J. Sweet, Robert G. Parton, Michael T. Ryan, Jose M. Polo, Christian M. Nefzger () and Susan K. Nilsson ()
Additional contact information
Xuan Sun: Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Benjamin Cao: Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Marina Naval-Sanchez: The University of Queensland
Tony Pham: The University of Queensland
Yu Bo Yang Sun: Monash University
Brenda Williams: Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Shen Y. Heazlewood: Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Nikita Deshpande: The University of Queensland
Jinhua Li: Monash Biomedicine Discovery Institute
Felix Kraus: Monash Biomedicine Discovery Institute
James Rae: The University of Queensland
Quan Nguyen: The University of Queensland
Hamed Yari: The University of Queensland
Jan Schröder: Monash University
Chad K. Heazlewood: Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Madeline Fulton: Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Jessica Hatwell-Humble: Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Kaustav Gupta: The University of Queensland
Ronan Kapetanovic: The University of Queensland
Xiaoli Chen: The University of Queensland
Matthew J. Sweet: The University of Queensland
Robert G. Parton: The University of Queensland
Michael T. Ryan: Monash Biomedicine Discovery Institute
Jose M. Polo: Monash University
Christian M. Nefzger: Monash University
Susan K. Nilsson: Biomedical Manufacturing Commonwealth Scientific and Industrial Research Organisation (CSIRO)

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22863-0

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