Mobilization-based transplantation of young-donor hematopoietic stem cells extends lifespan in mice.,Aging Cell

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Mobilization-based transplantation of young-donor hematopoietic stem cells extends lifespan in mice.
Aging Cell ( IF 8.0 ) Pub Date : 2020-02-03 , DOI: 10.1111/acel.13110
Michael J Guderyon ₁ , Cang Chen ₁ , Anindita Bhattacharjee ₁ , Guo Ge ₁ , Roman A Fernandez ₂ , Jonathan A L Gelfond ₂ , Karla M Gorena ₃ , Catherine J Cheng _{4,

5} , Yang Li ₆ , James F Nelson _{5,

7} , Randy J Strong _{5,

8,

9} , Peter J Hornsby _{5,

7} , Robert A Clark _{1,

9} , Senlin Li _{1,

5,

8,

9}

Affiliation

Mammalian aging is associated with reduced tissue regeneration and loss of physiological integrity. With age, stem cells diminish in their ability to regenerate adult tissues, likely contributing to age‐related morbidity. Thus, we replaced aged hematopoietic stem cells (HSCs) with young‐donor HSCs using a novel mobilization‐enabled hematopoietic stem cell transplantation (HSCT) technology as an alternative to the highly toxic conditioning regimens used in conventional HSCT. Using this approach, we are the first to report an increase in median lifespan (12%) and a decrease in overall mortality hazard (HR: 0.42, CI: 0.273–0.638) in aged mice following transplantation of young‐donor HSCs. The increase in longevity was accompanied by reductions of frailty measures and increases in food intake and body weight of aged recipients. Young‐donor HSCs not only preserved youthful function within the aged bone marrow stroma, but also at least partially ameliorated dysfunctional hematopoietic phenotypes of aged recipients. This compelling evidence that mammalian health and lifespan can be extended through stem cell therapy adds a new category to the very limited list of successful anti‐aging/life‐extending interventions. Our findings have implications for further development of stem cell therapies for increasing health and lifespan.

中文翻译：

基于动员的年轻供体造血干细胞移植可延长小鼠的寿命。

哺乳动物衰老与组织再生减少和生理完整性丧失有关。随着年龄的增长，干细胞再生成人组织的能力减弱，可能导致与年龄相关的发病率。因此，我们使用一种新型的动员造血干细胞移植 (HSCT) 技术，用年轻供体 HSC 取代了老化的造血干细胞 (HSC)，作为传统 HSCT 中使用的高毒性预处理方案的替代方案。使用这种方法，我们首次报告年轻供体 HSC 移植后老年小鼠的中位寿命增加 (12%) 且总体死亡风险降低 (HR: 0.42，CI: 0.273–0.638)。寿命的延长伴随着老年接受者虚弱指标的减少以及食物摄入量和体重的增加。年轻供体的造血干细胞不仅在老年骨髓基质内保留了年轻的功能，而且至少部分改善了老年受者的功能失调的造血表型。这一令人信服的证据表明，通过干细胞疗法可以延长哺乳动物的健康和寿命，这为非常有限的成功抗衰老/延长寿命干预措施的列表添加了一个新类别。我们的研究结果对进一步开发干细胞疗法以提高健康和寿命具有重要意义。

更新日期：2020-02-03

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