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

Maria Maryanovich, Ali H. Zahalka, Halley Pierce, Sandra Pinho, Fumio Nakahara, Noboru Asada, Qiaozhi Wei, Xizhe Wang, Paul Ciero, Jianing Xu, Avigdor Leftin, Paul S. Frenette

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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.

Original languageEnglish
Pages (from-to)782-791
Number of pages10
JournalNature Medicine
Volume24
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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. (2018). Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nature Medicine, 24(6), 782-791. https://doi.org/10.1038/s41591-018-0030-x