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

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外文摘要：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,CD1501ow 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.

作者：

Yuting Wang、Wenhao Zhang、Chao Zhang、Hoang Q.Tran Van、Takashi Seino、Yi Zhang

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作者单位：

Howard Hughes Medical Institute,Boston Children's Hospital,Boston,MA,USA

Program in Cellular and Molecular Medicine,Boston Children's Hospital,Boston,MA,USA

Division of Hematology/Oncology,Department of Pediatrics,Boston Children's Hospital,Boston,MA,USA

Department of Genetics,Harvard Medical School,Boston,MA,USA

Harvard Stem Cell Institute,Boston,MA,USA

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出版年：

2025

DOI：

10.1038/s41422-024-01057-5

细胞研究(英文版)

中国科学院上海生化细胞所

细胞研究(英文版)

影响因子：1.355

ISSN：

年,卷(期)：2025.35(1)