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Nat Med. 2018 Jun;24(6):782-791. doi: 10.1038/s41591-018-0030-x. Epub 2018 May 7.

Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche.

Author information

1
Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY, USA.
2
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY, USA.
3
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, NY, USA.
4
Okayama University Hospital, Department of Hematology and Oncology, Okayama, Japan.
5
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
6
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
7
Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, NY, USA. paul.frenette@einstein.yu.edu.
8
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY, USA. paul.frenette@einstein.yu.edu.
9
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, NY, USA. paul.frenette@einstein.yu.edu.

Abstract

Aging of hematopoietic stem cells (HSCs) is associated with a decline in their regenerative capacity and multilineage differentiation potential, contributing to the development of blood disorders. The bone marrow microenvironment has recently been suggested to influence HSC aging, but the underlying mechanisms remain largely unknown. Here we show that HSC aging critically depends on bone marrow innervation by the sympathetic nervous system (SNS), as loss of SNS nerves or adrenoreceptor β3 signaling in the bone marrow microenvironment of young mice led to premature HSC aging, as evidenced by appearance of HSC phenotypes reminiscent of physiological aging. Strikingly, supplementation of a sympathomimetic acting selectively on adrenoreceptor β3 to old mice significantly rejuvenated the in vivo function of aged HSCs, suggesting that the preservation or restitution of bone marrow SNS innervation during aging may hold the potential for new HSC rejuvenation strategies.

PMID:
29736022
PMCID:
PMC6095812
DOI:
10.1038/s41591-018-0030-x
[Indexed for MEDLINE]
Free PMC Article

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