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

doi:10.1038/s41591-018-0030-x

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

Research output: Contribution to journal › Article › peer-review

227 Scopus citations

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 language	English (US)
Pages (from-to)	782-791
Number of pages	10
Journal	Nature Medicine
Volume	24
Issue number	6
DOIs	https://doi.org/10.1038/s41591-018-0030-x
State	Published - Jun 1 2018

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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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.",

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AU - Zahalka, Ali H.

AU - Pierce, Halley

AU - Pinho, Sandra

AU - Nakahara, Fumio

AU - Asada, Noboru

AU - Wei, Qiaozhi

AU - Wang, Xizhe

AU - Ciero, Paul

AU - Xu, Jianing

AU - Leftin, Avigdor

AU - Frenette, Paul S.

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AB - 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.

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

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