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.

中文翻译：

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骨髓中的肾上腺能神经变性驱动造血干细胞小生境的衰老。

造血干细胞（HSC）的衰老与其再生能力和多系分化潜能的下降有关，从而导致血液疾病的发展。最近有人提出骨髓微环境会影响HSC的衰老，但其潜在机制仍是未知之数。在这里我们显示，HSC衰老严重依赖于交感神经系统（SNS）的骨髓神经支配，因为年轻小鼠骨髓微环境中SNS神经或肾上腺素受体β3信号的缺失导致HSC提前衰老，这由HSC的出现证明这些表型让人联想到生理衰老。令人惊讶的是，向老龄小鼠补充选择性作用于肾上腺素能受体3的拟交感神经药可显着恢复衰老的HSC的体内功能，