美国哈佛大学张毅研究小组发现，减少功能缺陷的老年HSC可缓解老年受体小鼠的衰老相关表型。相关论文于2025年1月2日在线发表于国际学术期刊《细胞研究》。

研究人员证明了将年轻的造血干细胞（HSC）移植到老年小鼠体内可以缓解衰老表型，突显了HSC在衰老过程中的关键作用。通过全面的分子和功能分析，研究人员在老年小鼠中发现了一部分具有“年轻”分子特征和功能的HSC，这些HSC的CD150表达水平较低。从机制上讲，来自老年小鼠的CD150低表达的HSC，而不是其CD150高表达的同类，能够有效地分化为下游谱系细胞。

值得注意的是，移植老年小鼠的CD150低表达HSC相比移植未经筛选或CD150高表达HSC的小鼠，可以减轻衰老表型并延长老年小鼠的寿命。更重要的是，减少功能失调的CD150高表达HSC可以缓解老年受体小鼠的衰老表型。因此，该研究表明，老年小鼠中存在“年轻”HSC，并且通过减少功能失调的HSC可以减轻衰老相关的功能衰退。

研究人员表示，衰老是一个伴随着组织和器官功能衰退的过程，具有重大的社会和医学后果。开发有效的抗衰老策略具有重要意义。

附：英文原文

Title: Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice

Author: Wang, Yuting, Zhang, Wenhao, Zhang, Chao, Van, Hoang Q. Tran, Seino, Takashi, Zhang, Yi

Issue&Volume: 2025-01-02

Abstract: Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Developing effective anti-aging strategies is of great significance. In this study, we demonstrated that transplantation of young hematopoietic stem cells (HSCs) into old mice can mitigate aging phenotypes, underscoring the crucial role of HSCs in the aging process. Through comprehensive molecular and functional analyses, we identified a subset of HSCs in aged mice that exhibit “younger” molecular profiles and functions, marked by low levels of CD150 expression. Mechanistically, CD150low HSCs from old mice but not their CD150high counterparts can effectively differentiate into downstream lineage cells. Notably, transplantation of old CD150low HSCs attenuates aging phenotypes and prolongs lifespan of elderly mice compared to those transplanted with unselected or CD150high HSCs. Importantly, reducing the dysfunctional CD150high HSCs can alleviate aging phenotypes in old recipient mice. Thus, our study demonstrates the presence of “younger” HSCs in old mice, and that aging-associated functional decline can be mitigated by reducing dysfunctional HSCs.

DOI: 10.1038/s41422-024-01057-5

Source: https://www.nature.com/articles/s41422-024-01057-5