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


Authors: Maryanovich, M.; Zahalka, A. H.; Pierce, H.; Pinho, S.; Nakahara, F.; Asada, N.; Wei, Q.; Wang, X.; Ciero, P.; Xu, J.; Leftin, A.; Frenette, P. S.
Article Title: Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche
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. © 2018 The Author(s).
Journal Title: Nature Medicine
Volume: 24
Issue: 6
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2018-06-01
Start Page: 782
End Page: 791
Language: English
DOI: 10.1038/s41591-018-0030-x
PROVIDER: scopus
PUBMED: 29736022
PMCID: PMC6095812
DOI/URL:
Notes: Correction issued, see DOI: 10.1038/s41591-019-0425-3 -- Article -- Export Date: 2 July 2018 -- Source: Scopus
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  1. Jianing Xu
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  2. Avigdor   Leftin
    9 Leftin