与食相关的AMPKγ1复合体活动是健康和寿命的标志
Roberto Ripa1, Eugen Ballhysa1,2, Joachim D Steiner1,3
1Max Planck Institute for Biology of Ageing, Cologne, Germany.
Nature aging
|November 13, 2023
概括
年龄较大的鱼类发展出持续的禁食状态,但持续的AMP激活蛋白激酶玛1 (AMPKγ1) 激活可以保持年轻人的代谢反应,改善健康和寿命.
科学领域:
- 老年学是一门学科.
- 代谢研究的研究.
- 分子生物学分子生物学
背景情况:
- 晚年生活中的饮食干预措施在促进长寿和减轻脆弱方面取得了有限的成功.
- 与年龄相关的代谢衰退和干预效率降低背后的分子机制尚未完全理解.
研究的目的:
- 为了研究鱼*Nothobranchius furzeri*中与年龄相关的禁食反应.
- 确定旨在维护代谢健康和促进健康衰老的干预措施的分子标.
主要方法:
- 在被和禁食状态下,对年轻和老鱼脂肪组织的转录组分析.
- 产生和分析具有持续AMPKγ1表达的转基因鱼.
- 对人类组织中AMPKγ1表达的分析及其与脆弱风险的关联.
主要成果:
- 老鱼在脂肪组织中表现出类似禁食的转录程序,导致代谢静止.
- 衰老破坏了AMPK子单元的禁食再诱导的振荡表达,减少了Prkag1的表达.
- 在转基因鱼中持续的AMPKγ1激活抵消了代谢静止,改善了代谢健康,并延长了寿命.
- 在人体组织中,随着年龄的增长,Prkag1表达的下降与多病症和脆弱性风险相关.
结论:
- 选择性激活AMPKγ1可以防止与年龄相关的代谢静止,并保持脊椎动物的健康衰老.
- AMPKγ1代表了针对与年龄相关的代谢功能障碍和虚弱的干预措施的潜在治疗标.
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