Department of Laboratory Medicine and Pathology, University of Washington Medical Center, 1959 NE Pacific St, Seattle, WA, 98195, USA.
Geroscience. 2021 Aug;43(4):1591-1604. doi: 10.1007/s11357-021-00365-7. Epub 2021 Apr 17.
Mitochondria are organelles that provide energy to cells through ATP production. Mitochondrial dysfunction has long been postulated to mediate cellular declines that drive biological aging. Many well-characterized hallmarks of aging may involve underlying energetic defects that stem from loss of mitochondrial function with age. Why and how mitochondrial function declines with age is an open question and one that has been difficult to answer. Mitochondria are powered by an electrochemical gradient across the inner mitochondrial membrane known as the protonmotive force (PMF). This gradient decreases with age in several experimental models. However, it is unclear if a diminished PMF is a cause or a consequence of aging. Herein, we briefly review and define mitochondrial function, we summarize how PMF changes with age in several models, and we highlight recent studies that implicate PMF in aging biology. We also identify barriers that must be addressed for the field to progress. Emerging technology permits more precise in vivo study of mitochondria that will allow better understanding of cause and effect in metabolic models of aging. Once cause and effect can be discerned more precisely, energetics approaches to combat aging may be developed to prevent or reverse functional decline.
线粒体是通过 ATP 生成为细胞提供能量的细胞器。线粒体功能障碍长期以来被认为介导了导致生物衰老的细胞衰退。许多特征明显的衰老标志可能涉及潜在的能量缺陷，这些缺陷源于随年龄增长而导致的线粒体功能丧失。为什么以及线粒体功能随年龄增长而下降是一个悬而未决的问题，也是一个难以回答的问题。线粒体由跨线粒体内膜的电化学梯度提供动力，称为质子动力势 (PMF)。在几个实验模型中，这种梯度随年龄的增长而降低。然而，目前尚不清楚 PMF 的降低是衰老的原因还是结果。在此，我们简要回顾和定义线粒体功能，总结几个模型中 PMF 随年龄的变化，并强调最近的研究表明 PMF 与衰老生物学有关。我们还确定了该领域需要解决的障碍。新兴技术允许对代谢衰老模型中的线粒体进行更精确的体内研究，从而更好地理解因果关系。一旦能够更精确地辨别因果关系，就可以开发出对抗衰老的能量学方法来预防或逆转功能衰退。
