TY - JOUR
T1 - NAD+ augmentation with nicotinamide riboside improves lymphoid potential of Atm −/− and old mice HSCs
AU - Zong, Le
AU - Tanaka-Yano, Mayuri
AU - Park, Bongsoo
AU - Yanai, Hagai
AU - Turhan, Ferda T.
AU - Croteau, Deborah L.
AU - Tian, Jane
AU - Fang, Evandro F.
AU - Bohr, Vilhelm A.
AU - Beerman, Isabel
N1 - Funding Information:
The authors would like to thank all members of the Epigenetic and Stem Cell Unit and Experimental Gerontology Section of the NIA. The authors would also like to acknowledge the support of William Wood and all of the Genetics and Genomics Core at the NIA for their assistance. I.B. and V.A.B. were supported by the Intramural Research Program of the NIH, National Institute on Aging. The authors would like to specially thank Elizabeth Beerman for editing efforts. E.F.F. was supported by HELSE Sør-Øst (#2017056), The Research Council of Norway (#262175), Rosa Sløyfe & Norwegian Breast Cancer Society (#207819), and NSFC (#81971327). M.T.-Y. was supported by the Intramural Research Program of NIA and Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH.
Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - NAD+ supplementation has significant benefits in compromised settings, acting largely through improved mitochondrial function and DNA repair. Elevating NAD+ to physiological levels has been shown to improve the function of some adult stem cells, with implications that these changes will lead to sustained improvement of the tissue or system. Here, we examined the effect of elevating NAD+ levels in models with reduced hematopoietic stem cell (HSC) potential, ATM-deficient and aged WT mice, and showed that supplementation of nicotinamide riboside (NR), a NAD+ precursor, improved lymphoid lineage potential during supplementation. In aged mice, this improved lymphoid potential was maintained in competitive transplants and was associated with transcriptional repression of myeloid gene signatures in stem and lineage-committed progenitor cells after NR treatment. However, the altered transcriptional priming of the stem cells toward lymphoid lineages was not sustained in the aged mice after NR removal. These data characterize significant alterations to the lineage potential of functionally compromised HSCs after short-term exposure to NR treatment.
AB - NAD+ supplementation has significant benefits in compromised settings, acting largely through improved mitochondrial function and DNA repair. Elevating NAD+ to physiological levels has been shown to improve the function of some adult stem cells, with implications that these changes will lead to sustained improvement of the tissue or system. Here, we examined the effect of elevating NAD+ levels in models with reduced hematopoietic stem cell (HSC) potential, ATM-deficient and aged WT mice, and showed that supplementation of nicotinamide riboside (NR), a NAD+ precursor, improved lymphoid lineage potential during supplementation. In aged mice, this improved lymphoid potential was maintained in competitive transplants and was associated with transcriptional repression of myeloid gene signatures in stem and lineage-committed progenitor cells after NR treatment. However, the altered transcriptional priming of the stem cells toward lymphoid lineages was not sustained in the aged mice after NR removal. These data characterize significant alterations to the lineage potential of functionally compromised HSCs after short-term exposure to NR treatment.
UR - http://www.scopus.com/inward/record.url?scp=85115366123&partnerID=8YFLogxK
U2 - 10.1038/s41514-021-00078-3
DO - 10.1038/s41514-021-00078-3
M3 - Article
C2 - 34548492
AN - SCOPUS:85115366123
SN - 2056-3973
VL - 7
JO - npj Aging and Mechanisms of Disease
JF - npj Aging and Mechanisms of Disease
IS - 1
M1 - 25
ER -