Autophagy as a promoter of longevity: insights from model organisms.
Autophagy as a promoter of longevity: insights from model organisms.
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DOI：
10.1038/s41580-018-0033-y
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Walker DW
中科院分区：
文献类型：
--
作者：
Hansen M;Rubinsztein DC;Walker DW
自噬是一个保守的过程，分解代谢细胞内的成分，以维持能量稳态，并保护细胞免受压力。自噬在发育和疾病过程中起着至关重要的作用，过去十年积累的证据表明，自噬在调节衰老方面也有直接作用。特别是，使用酵母，蠕虫，苍蝇和小鼠的优雅研究已经证明了在许多保守的长寿范例中观察到的寿命延长中对自噬相关基因的广泛需求。此外，一些新的和有趣的概念相关的自噬及其在调节寿命的作用已经出现。首先，选择组织可能需要或受益于长寿范例中的自噬激活，因为单个自噬基因的组织特异性过表达足以延长寿命。其次，选择性自噬类型可能对长寿至关重要，因为它特异性地靶向功能失调的细胞成分并防止它们的积累。第三，自噬可以影响生物体的健康和衰老，甚至是非细胞自主的，因此，在选定的组织中刺激自噬可以对寿命产生有益的全身性影响。了解这些机制对于开发基于自噬调节的改善人类健康的方法将是重要的。
Autophagy is a conserved process that catabolizes intracellular components to maintain energy homeostasis and to protect cells against stress. Autophagy has crucial roles during development and disease, and evidence accumulated over the past decade indicates that autophagy also has a direct role in modulating ageing. In particular, elegant studies using yeasts, worms, flies and mice have demonstrated a broad requirement for autophagy-related genes in the lifespan extension observed in a number of conserved longevity paradigms. Moreover, several new and interesting concepts relevant to autophagy and its role in modulating longevity have emerged. First, select tissues may require or benefit from autophagy activation in longevity paradigms, as tissue-specific overexpression of single autophagy genes is sufficient to extend lifespan. Second, selective types of autophagy may be crucial for longevity by specifically targeting dysfunctional cellular components and preventing their accumulation. And third, autophagy can influence organismal health and ageing even non-cell autonomously, and thus, autophagy stimulation in select tissues can have beneficial, systemic effects on lifespan. Understanding these mechanisms will be important for the development of approaches to improve human healthspan that are based on the modulation of autophagy.
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