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 Das Gupta, Ronan Kapetanovic, Xiaoli ChenMatthew J. Sweet, Robert G. Parton, Michael T. Ryan, Jose M. Polo, Christian M. Nefzger, Susan K. Nilsson

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38 Citations (Scopus)

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.

Original languageEnglish
Article number2665
Number of pages17
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

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