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PDK4依赖的超级catabolism和衰老细胞的乳酸生产促进癌症恶性瘤
Xuefeng Dou1, Qiang Fu2, Qilai Long3
1Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Nature metabolism
|October 31, 2023
概括
细胞衰老涉及酸盐脱酶激酶4 (PDK4) 的增加,导致有氧糖解和乳酸盐生产. 抑制PDK4可以减少癌症恶性和与年龄相关的脆弱性.
科学领域:
- 细胞衰老 细胞衰老
- 代谢重编程是一种代谢重编程.
- 与年龄有关的病理.
背景情况:
- 衰老细胞在代谢上是活跃的,但它们的代谢重编程尚未完全理解.
- 酸盐脱酶激酶4 (PDK4) 在衰老中的作用尚未得到充分研究.
研究的目的:
- 研究衰老细胞的代谢场景.
- 确定PDK4在衰老中的作用及其对癌症和衰老的影响.
主要方法:
- 在衰老细胞中分析PDK4表达.
- 评估新陈代谢变化,包括有氧糖解和乳酸生产.
- 在癌症模型中使用PDK4抑制的体外和体内研究.
- 临床前试验评估PDK4抑制与年龄相关的功能障碍.
主要成果:
- 衰老调节PDK4,增加有氧糖解和乳酸生产.
- 衰老细胞产生的乳酸通过NOX1诱导的ROS促进癌细胞恶性瘤.
- 抑制PDK4可以减少瘤生长,DNA损伤和与衰老相关的分泌表型.
- 在临床前模型中,PDK4抑制可缓解身体功能障碍,并防止脆弱性.
结论:
- 衰老细胞表现出PDK4依赖的代谢重编程,其特征是有氧糖解增加.
- 细胞衰老,乳酸生产和癌症等与年龄相关的疾病之间存在代谢联系.
- 向PDK4为癌症和与年龄相关的疾病提供了潜在的治疗策略.
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