School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Adv Exp Med Biol. 2012;942:311-27. doi: 10.1007/978-94-007-2869-1_14.
Aging is a degenerative process that is associated with progressive accumulation of deleterious changes with time, reduction of physiological function and increase in the chance of disease and death. Studies in several species reveal a wide spectrum of alterations in mitochondria and mitochondrial DNA (mtDNA) with aging, including (1) increased disorganization of mitochondrial structure, (2) decline in mitochondrial oxidative phosphorylation (OXPHOS) function, (3) accumulation of mtDNA mutation, (4) increased mitochondrial production of reactive oxygen species (ROS) and (5) increased extent of oxidative damage to DNA, proteins, and lipids. In this chapter, we outline the common alterations in mitochondria of the aging tissues and recent advances in understanding the role of mitochondrial H(2)O(2) production and mtDNA mutation in the aging process and lifespan determination. In addition, we discuss the effect of caloric restriction on age-associated mitochondrial changes and its role in longevity. Taking these findings together, we suggest that decline in mitochondrial energy metabolism, enhanced mitochondrial oxidative stress, and accumulation of mtDNA mutations are important contributors to human aging.
衰老是一种退行性过程,与随着时间的推移有害变化的逐渐积累、生理功能的降低以及疾病和死亡的几率增加有关。在几种物种中的研究揭示了与衰老相关的线粒体和线粒体 DNA(mtDNA)的广泛变化,包括(1)线粒体结构的紊乱增加,(2)线粒体氧化磷酸化(OXPHOS)功能下降,(3)mtDNA 突变的积累,(4)线粒体产生的活性氧(ROS)增加,以及(5)DNA、蛋白质和脂质的氧化损伤程度增加。在本章中,我们概述了衰老组织中线粒体的常见变化,并介绍了理解线粒体 H(2)O(2)产生和 mtDNA 突变在衰老过程和寿命决定中的作用的最新进展。此外,我们还讨论了热量限制对与年龄相关的线粒体变化的影响及其在长寿中的作用。综上所述,我们认为线粒体能量代谢的下降、增强的线粒体氧化应激以及 mtDNA 突变的积累是导致人类衰老的重要因素。