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影响人类和动物模型寿命的 G 蛋白偶联受体。

G protein-coupled receptors that influence lifespan of human and animal models.

机构信息

Department of Neuroscience, Functional Pharmacology, Uppsala University, Husargatan 3, BMC Box 593, 751 24, Uppsala, Sweden.

出版信息

Biogerontology. 2022 Feb;23(1):1-19. doi: 10.1007/s10522-021-09945-8. Epub 2021 Dec 3.

Abstract

Humanity has always sought to live longer and for this, multiple strategies have been tried with varying results. In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while maintaining good health since they have a substantial participation in a wide variety of processes of human pathophysiology and are one of the main therapeutic targets. In this way, we present the analysis of a series of GPCRs whose activity has been shown to affect the lifespan of animal and human models, and in which we put a special interest in describing the molecular mechanisms involved. Our compilation of data revealed that the mechanisms most involved in the role of GPCRs in lifespan are those that mimic dietary restriction, those related to insulin signaling and the AMPK and TOR pathways, and those that alter oxidative homeostasis and severe and/or chronic inflammation. We also discuss the possibility of using agonist or antagonist drugs, depending on the beneficial or harmful effects of each GPCR, in order to prolong people's lifespan and healthspan.

摘要

人类一直以来都在寻求长寿,为此,人们尝试了多种策略,取得了不同的效果。从这个意义上说,G 蛋白偶联受体 (GPCR) 可能是一个不错的选择,可以尝试在保持身体健康的同时延长我们的寿命,因为它们在广泛的人类病理生理学过程中具有实质性的参与,并且是主要的治疗靶点之一。 为此,我们分析了一系列 GPCR,其活性已被证明会影响动物和人类模型的寿命,我们特别关注描述涉及的分子机制。我们的数据汇编表明,GPCR 在寿命中起作用的机制最涉及模拟饮食限制的机制、与胰岛素信号和 AMPK 和 TOR 途径相关的机制,以及改变氧化平衡和严重和/或慢性炎症的机制。我们还讨论了根据每种 GPCR 的有益或有害影响使用激动剂或拮抗剂药物的可能性,以延长人们的寿命和健康寿命。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a183/8888397/673d2dad175a/10522_2021_9945_Fig1_HTML.jpg

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