Journal article

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 Schroder, Chad K Heazlewood, Madeline Fulton, Jessica Hatwell-Humble, Kaustav Das Gupta, Ronan Kapetanovic, Xiaoli Chen Show all

NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2021

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 ..

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Grants

Awarded by new Investigator NHMRC project grant


Funding Acknowledgements

We thank Monash Animal Services, in particular, Jennifer Flores for help with animal husbandry as well as the University of Queensland animal facilities at the Australian Institute for Bioengineering and Nanotechnology and the Queensland Brain Institute. We further acknowledge Dani Cardozo for animal assistance. We acknowledge Dr Christopher K. Barlow, Monash Proteomics and Metabolomics Facility, Monash University, for Metabolomic analysis. We thank FlowCore (Monash University), the TRI Flowcytometry facility (University of Queensland) and the Micro Imaging facilities at Monash University and the Institute for Molecular Bioscience at the University of Queensland for their high quality scientific and technical assistance. We acknowledge the ACRF Centre for Cancer Genomics Medicine at the MHTP Medical Genomics Facility for next-generation library preparation and Illumina sequencing. We thank Patrick Tam and Klaus Matthaei for the provision of RFP and enhanced GFP mice, respectively. In addition, we want to acknowledge Chromadex for kindly providing us with NIAGEN (R) nicotinamide riboside. S.K.N. was supported by an ARC Future Fellowship and a CSIRO OCE Science Leader Fellowship; C.M.N. was supported by a new Investigator NHMRC project grant (APP1146623) and start-up funding from the University of Queensland, X.S. was supported by a CSIRO OCE Post-doctoral Fellowship. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government.