Donati Alessio, Taddei Michele, Cavallini Gabriella, Bergamini Ettore
Center for Research on Biology and Pathology of Aging, University of Pisa, Pisa, Italy.
Rejuvenation Res. 2006 Fall;9(3):408-12. doi: 10.1089/rej.2006.9.408.
Reduction of oxidative stress within mitochondria is a major focus and important part in the SENS agenda. The age-related accumulation of mitochondria rich in oxidatively altered DNA may be a biomarker of malfunctioning and increased oxidative stress. Macroautophagy is the cell repair mechanism responsible for the disposal of excess or altered mitochondria under the inhibitory control of nutrition and insulin, and may mediate the antiaging effects of caloric restriction. The authors investigated the effects of stimulation of macroautophagy by the injection of an antilipolytic agent on the age-related accumulation of oxidatively altered mitochondrial DNA (mtDNA) in rat liver cells. Results showed that treatment rescued older cells from the accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the mtDNA in less than 6 hours. It is concluded that the age-related changes in mtDNA and function are likely to be the consequence of a failure of macroautophagy in the recognition and disposal of a small number of severely injured mitochondria, and that easy and safe ways are available to counteract this change.
减少线粒体内的氧化应激是“工程可实现的抗衰老策略”（SENS）议程的主要关注点和重要组成部分。富含氧化改变DNA的线粒体随年龄增长而积累，这可能是功能失调和氧化应激增加的生物标志物。巨自噬是一种细胞修复机制，在营养和胰岛素的抑制控制下负责处理多余或改变的线粒体，并且可能介导热量限制的抗衰老作用。作者研究了注射抗脂解剂刺激巨自噬对大鼠肝细胞中氧化改变的线粒体DNA（mtDNA）随年龄增长积累的影响。结果表明，治疗在不到6小时内使老年细胞免受mtDNA中8-羟基-2'-脱氧鸟苷（8-OHdG）的积累。结论是，mtDNA和功能的年龄相关变化可能是巨自噬在识别和处理少数严重受损线粒体方面失败的结果，并且有简单安全的方法可以抵消这种变化。
