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RNA聚合酶III限制了TORC1下游的寿命

Danny Filer¹, Maximillian A Thompson², Vakil Takhaveev³

¹Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK.

|November 30, 2017

概括

降低RNA聚合酶III (Pol III) 活性可以延长酵母,虫和的寿命. 这种由TORC1调节的关键酶影响衰老,可能是长寿的治疗点.

科学领域:

分子生物学
遗传学
老龄化研究

背景情况:

细胞转录涉及三个不同的RNA聚合酶 (Pol I,II,III).
RNA聚合酶III (Pol III) 转录重要的小型非编码RNA (例如tRNA,5SrRNA).
尽管它受到TORC1的调节,但Pol III在生物体生理和衰老中的作用仍然很大程度上未被探索,这是已知的长寿决定因素.

研究的目的:

研究RNA聚合酶III (Pol III) 在生物衰老中的作用.
确定Pol III活动是否影响TORC1信号通路下游的寿命.
探索Pol III作为长寿治疗目标的潜力.

主要方法:

在酵母,C. elegans和Drosophila melanogaster中进行寿命测定.
基因和药物抑制Pol III活动.
对老年生物的肠道病理,蛋白质合成和蛋白质静止应激耐受性的分析.
调查Pol III在寿命调节中的TORC1信号的位置.

主要成果:

减少Pol III的活性显著延长了酵母的时间寿命和虫和的生物寿命.
特别是在成年肠道中抑制Pol III,甚至在中抑制肠道干细胞,足以促进寿命.
长寿表型与改善肠道健康,减少蛋白质合成和增强蛋白质稳定有关.
在TORC1下游作用,调解TORC1的抗衰老作用.

结论:

RNA聚合酶III (Pol III) 是衰老的关键调解剂,作用于TORC1的下游.
限制Pol III活动,特别是在肠道,延长寿命和改善与年龄相关的衰退.
波尔III的进化保护表明它有可能成为促进长寿和健康的可用目标.

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