Reconsidering the Role of Mitochondria in Aging
Reconsidering the Role of Mitochondria in Aging
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DOI：
10.1093/gerona/glv070
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发表时间：
2015-11-01
影响因子：
5.1
通讯作者：
Ferrucci, Luigi
中科院分区：
文献类型：
--
作者：
Gonzalez-Freire, Marta;de Cabo, Rafael;Ferrucci, Luigi
背景：线粒体功能障碍一直被认为是衰老和老年相关疾病的主要因素。Harman的线粒体自由基衰老理论认为，在人的一生中积累的体细胞线粒体DNA突变会导致过量产生活性氧物种，从而破坏大分子并损害细胞和组织功能。事实上，研究表明，最大氧化能力随着年龄的增长而下降，而活性氧类的产生则增加。哈曼的假设受到了严重挑战，因为最近的研究表明，活性氧能促进新陈代谢的健康和长寿，可能是通过包括自噬在内的兴奋机制。该综述的目的是从衰老研究的角度浏览日益增长的线粒体文献，并试图确定未来研究中应解决的优先问题。方法：使用PubMed对同行评议的研究进行系统检索。检索词包括(I)线粒体或线粒体；(Ii)衰老、衰老、老年人或老年人；(Iii)活性氧、线粒体动力学、线粒体蛋白平衡、胞浆、线粒体相关膜、氧化还原稳态、电子传输链、电子传输链效率、表观遗传调控、DNA异质性。结果：线粒体生物学作为衰老基础生物学和老年相关疾病发病机制之间的特征结合，其重要性比以往任何时候都更加重要，尽管重点已从活性氧的产生转移到线粒体生理学的其他方面，包括线粒体的生物发生和周转、能量感知、细胞凋亡、衰老和钙动力学。结论：线粒体可能在衰老的病理生理学过程中或在导致衰老表型的某些事件的早期阶段发挥关键作用。因此，线粒体将越来越有针对性地预防和治疗慢性病，促进健康老龄化。
Background: Mitochondrial dysfunction has long been considered a major contributor to aging and age-related diseases. Harman's Mitochondrial Free Radical Theory of Aging postulated that somatic mitochondrial DNA mutations that accumulate over the life span cause excessive production of reactive oxygen species that damage macromolecules and impair cell and tissue function. Indeed, studies have shown that maximal oxidative capacity declines with age while reactive oxygen species production increases. Harman's hypothesis has been seriously challenged by recent studies showing that reactive oxygen species evoke metabolic health and longevity, perhaps through hormetic mechanisms that include autophagy. The purpose of this review is to scan the ever-growing literature on mitochondria from the perspective of aging research and try to identify priority questions that should be addressed in future research.Methods: A systematic search of peer-reviewed studies was performed using PubMed. Search terms included (i) mitochondria or mitochondrial; (ii) aging, ageing, older adults or elderly; and (iii) reactive oxygen species, mitochondria dynamics, mitochondrial proteostasis, cytosol, mitochondrial-associated membranes, redox homeostasis, electron transport chain, electron transport chain efficiency, epigenetic regulation, DNA heteroplasmy.Results: The importance of mitochondrial biology as a trait d'union between the basic biology of aging and the pathogenesis of age-related diseases is stronger than ever, although the emphasis has moved from reactive oxygen species production to other aspects of mitochondrial physiology, including mitochondrial biogenesis and turnover, energy sensing, apoptosis, senescence, and calcium dynamics. Conclusions: Mitochondria could play a key role in the pathophysiology of aging or in the earlier stages of some events that lead to the aging phenotype. Therefore, mitochondria will increasingly be targeted to prevent and treat chronic diseases and to promote healthy aging.