Rejuvenation of the reconstitution potential and reversal of myeloid bias of aged HSCs upon pH treatment

IF 7.8 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Aging Cell Pub Date : 2024-09-05 DOI:10.1111/acel.14324
Sachin Kumar, Jeffrey D. Vassallo, Kalpana J. Nattamai, Aishlin Hassan, Angelika Vollmer, Rebekah Karns, Mehmet Sacma, Travis Nemkov, Angelo D'Alessandro, Hartmut Geiger
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引用次数: 0

Abstract

Aged hematopoietic stem cells (HSCs) show reduced reconstitution potential, limiting their use in transplantation settings in the clinic. We demonstrate here that exposure of aged HSCs ex vivo to a pH of 6.9 instead of the commonly used pH of 7.4 results in enhanced HSCs potential that is consistent with rejuvenation, including attenuation of the myeloid bias of aged HSC and restoration of a youthful frequency of epigenetic polarity. Rejuvenation of aged HSCs by pH 6.9 is, at least in part, due to alterations in the polyamine/methionine pathway within pH 6.9 HSCs, and consequently, attenuation of the production of spermidine also attenuated aging of HSCs. Exposure of aged HSCs to pH 6.9, or pharmacological targeting of the polyamine pathway, might thus extend the use of HSCs from aged donors for therapeutic applications.

Abstract Image

Abstract Image

pH 处理可恢复老化造血干细胞的重组潜能并逆转其骨髓偏向。
衰老的造血干细胞(HSCs)重建潜力降低,限制了它们在临床移植中的应用。我们在此证明,将体内老化造血干细胞暴露于 pH 值为 6.9 的环境中,而不是常用的 pH 值为 7.4 的环境中,会增强造血干细胞的潜力,这与年轻化是一致的,包括减弱老化造血干细胞的髓系偏向,恢复表观遗传极性的年轻化频率。pH 6.9能使衰老的造血干细胞恢复青春,至少部分原因是pH 6.9造血干细胞内的多胺/蛋氨酸途径发生了改变,因此,减少精胺的产生也能减轻造血干细胞的衰老。因此,将衰老的造血干细胞暴露于pH 6.9,或以多胺途径为药物靶点,可能会扩大来自衰老供体的造血干细胞在治疗方面的应用。
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来源期刊
Aging Cell
Aging Cell 生物-老年医学
CiteScore
14.40
自引率
2.60%
发文量
212
审稿时长
8 weeks
期刊介绍: Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.
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