Adrenergic Nerve Degeneration in Bone Marrow Drives Aging of the Hematopoietic Stem Cell Niche

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2018 May 9

PMID 29736022

Citations 177

Authors

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

Affiliations

Soon will be listed here.

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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