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与年龄相关的 AMP 激活蛋白激酶变化:从细胞能量学到长寿。

Age-related AMP-activated protein kinase alterations: From cellular energetics to longevity.

机构信息

Evolutionary Cytogerontology Sector, School of Biology, Lomonosov Moscow State University, Moscow, Russia.

出版信息

Cell Biochem Funct. 2019 Apr;37(3):169-176. doi: 10.1002/cbf.3384. Epub 2019 Mar 21.

Abstract

5' adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of energy in the cell, which allows the cell/organism to survive with deficit of ATP. Since AMPK is involved in the adaptation to caloric restriction, the role of age-related changes in AMPK activity in both the aging organism and the aging cell is actively investigated in gerontology. Studies on yeast, worms, flies, rodents, and primates have demonstrated an important effect of this regulator on key signalling pathways involved in the aging process. In some cases, researchers conclude that AMPK promotes aging. However, in our opinion, in such cases, we observe a disturbance in the adaptive ability because of the prolonged cell/organism presence in stressful conditions because the functional capacity of any adaptation system is limited. Interestingly, AMPK can regulate metabolic processes in noncell-autonomous manner. The main effects of AMPK activation in the cell are realized in restriction of proliferation and launching autophagy. In tissues of an aging organism, the ability of AMPK to respond to energy deficit decreases; this fact is especially critical for organs that contain postmitotic cells. In this review, we have tried to consider the involvement of AMPK in age-related changes in the cell and in the organism.

摘要

5' 腺苷单磷酸激活的蛋白激酶(AMPK)是细胞能量的关键调节剂,使细胞/机体在 ATP 缺乏的情况下能够存活。由于 AMPK 参与了热量限制的适应,因此在衰老生物学中,积极研究了与年龄相关的 AMPK 活性变化在衰老机体和衰老细胞中的作用。对酵母、蠕虫、苍蝇、啮齿动物和灵长类动物的研究表明,这种调节剂对参与衰老过程的关键信号通路有重要影响。在某些情况下,研究人员得出结论认为 AMPK 促进了衰老。然而,在我们看来,在这种情况下,我们观察到由于细胞/机体在应激条件下长时间存在而导致适应性能力受到干扰,因为任何适应系统的功能能力都是有限的。有趣的是,AMPK 可以以非细胞自主的方式调节代谢过程。AMPK 在细胞中的主要作用是限制增殖和启动自噬。在衰老机体的组织中,AMPK 对能量缺乏的反应能力下降;这一事实对含有有丝分裂后细胞的器官尤为关键。在这篇综述中,我们试图考虑 AMPK 参与细胞和机体与年龄相关的变化。

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