重新审视线粒体在衰老过程中的作用。
Reconsidering the Role of Mitochondria in Aging.
作者信息
Gonzalez-Freire Marta, de Cabo Rafael, Bernier Michel, Sollott Steven J, Fabbri Elisa, Navas Placido, Ferrucci Luigi
机构信息
Translational Gerontology Branch, and
Translational Gerontology Branch, and.
出版信息
J Gerontol A Biol Sci Med Sci. 2015 Nov;70(11):1334-42. doi: 10.1093/gerona/glv070. Epub 2015 May 20.
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.
背景
长期以来，线粒体功能障碍一直被认为是衰老及与年龄相关疾病的主要促成因素。哈曼的线粒体自由基衰老理论假定，在整个生命过程中积累的体细胞线粒体DNA突变会导致活性氧过度产生，从而损害大分子并削弱细胞和组织功能。事实上，研究表明，最大氧化能力会随着年龄增长而下降，而活性氧的产生则会增加。哈曼的假说受到了近期研究的严峻挑战，这些研究表明活性氧或许通过包括自噬在内的应激机制促进代谢健康和延长寿命。本综述的目的是从衰老研究的角度审视关于线粒体不断增长的文献，并试图确定未来研究中应解决的重点问题。
方法
使用PubMed对同行评审研究进行系统检索。检索词包括：(i)线粒体或线粒体的；(ii)衰老、老龄化、老年人；(iii)活性氧、线粒体动力学、线粒体蛋白质稳态、细胞质、线粒体相关膜、氧化还原稳态、电子传递链、电子传递链效率、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与年龄相关疾病发病机制之间的共同特征，其重要性比以往任何时候都更为突出，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，包括线粒体生物发生与更新、能量感应、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，线粒体将越来越多地成为预防和治疗慢性疾病以及促进健康衰老的靶点。
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