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自可以抵消在衰老的造血干细胞中由炎症驱动的糖溶性损伤
bioRxiv : the preprint server for biology
|August 30, 2023
概括
由于炎症驱动的代谢变化,衰老会损害造血干细胞 (HSC). 通过暂时禁食来激活自可以恢复高血糖细胞的功能,并在老年人中改善其再生潜力.
科学领域:
- 血液学 血液学 血液学
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 造血干细胞 (HSC) 功能障碍是衰老的标志,导致各种血液和免疫疾病.
- 自在HSC功能,寿命和对代谢压力的反应中发挥着关键作用.
- 虽然一些老年HSC可以调节自来维持功能,但信号和机制仍然不清楚.
研究的目的:
- 在慢性炎症的背景下,研究老年HSC中自的作用.
- 阐明炎症影响HSC代谢和功能的机制.
- 确定调节自能能否恢复老年高血压细胞的再生能力.
主要方法:
- 来自骨髓利基的老年HSC中自流的分析.
- 在老年HSC中研究葡萄糖代谢和糖解.
- 对AKT/FoxO信号和Socs3表达的评估.
- 实验性诱导自,使用禁食/再食模式.
- 在干预后评估HSC再生潜力.
主要成果:
- 在老化骨髓利基的慢性炎症促进自作为HSC的生存反应.
- 炎症通过Socs3-介导的AKT/FoxO信号的抑制损害了HSC糖解.
- 自的激活使代谢适应糖溶性损伤,保持HSC静止.
- 通过禁食/再的过渡性自诱导使葡萄糖代谢正常化,并显著增强老年HSC再生.
结论:
- 炎症诱导的葡萄糖低代谢是衰老期间HSC功能障碍的重要驱动因素.
- 自是HSC适应代谢压力和炎症的关键调解者.
- 向自是一种有前途的策略,可以恢复老年HSCs的代谢和再生能力.
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