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区分因果关系:胰岛素/胰岛素样生长因子信号通路如何控制线虫、果蝇和小鼠的寿命?

Separating cause from effect: how does insulin/IGF signalling control lifespan in worms, flies and mice?

作者信息

Piper M D W, Selman C, McElwee J J, Partridge L

机构信息

Centre for Research on Ageing, Department of Biology, University College London, London, UK.

出版信息

J Intern Med. 2008 Feb;263(2):179-91. doi: 10.1111/j.1365-2796.2007.01906.x.

Abstract

Ageing research has been revolutionized by the use of model organisms to discover genetic alterations that can extend lifespan. In the last 5 years alone, it has become apparent that single gene mutations in the insulin and insulin-like growth-factor signalling pathways can lengthen lifespan in worms, flies and mice, implying evolutionary conservation of mechanisms. Importantly, this research has also shown that these mutations can keep the animals healthy and disease-free for longer and can alleviate specific ageing-related pathologies. These findings are striking in view of the negative effects that disruption of these signalling pathways can also produce. Here, we summarize the body of work that has lead to these discoveries and point out areas of interest for future work in characterizing the genetic, molecular and biochemical details of the mechanisms to achieving a longer and healthier life.

摘要

衰老研究因利用模式生物来发现可延长寿命的基因改变而发生了变革。仅在过去5年里,胰岛素及胰岛素样生长因子信号通路中的单基因突变能够延长线虫、果蝇和小鼠的寿命这一点就已变得很明显,这暗示了相关机制在进化上的保守性。重要的是,这项研究还表明,这些突变可以使动物在更长时间内保持健康且无疾病,并能缓解特定的与衰老相关的病症。鉴于这些信号通路的破坏也会产生负面影响,这些发现令人瞩目。在此,我们总结了促成这些发现的一系列研究工作,并指出了未来研究的兴趣领域,这些研究旨在阐明实现更长寿、更健康生活的机制在基因、分子和生化方面的细节。

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