Stimulation of Macroautophagy Can Rescue Older Cells from 8-OHdG mtDNA Accumulation: A Safe and Easy Way to Meet Goals in the SENS Agenda

Abstract

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.