Dietary restriction augments resistance to oxidant-mediated inhibition of mitochondrial transcription.

The exquisite sensitivity of mitochondrial transcription to oxidant stress suggests that chronic, low level oxidative stress may impair mitochondrial gene expression during the aging process. In this study, we assessed the effects of age and of life-prolonging, anti-oxidative dietary restriction (DR) regimens on sensitivity of mitochondrial transcription to oxidant stress. Studies were carried out using liver mitochondria isolated from male Fischer 344 rats of different ages (6, 12, 18, or 24 months) fed ad libitum (AL) or maintained on DR. Transcriptional capacity was assessed in isolated mitochondria challenged with different doses of either hydrophilic or hydrophobic peroxyl radicals generated by AAPH [2,2'-azobis-(2-amidino-propane) hydrochloride] or AMVN [2, 2'-azobis-(2,4,-dimethyl-valeronitrile), respectively]. The most striking effect was that DR increased resistance to AMVN nearly 400% at 6 months and nearly 700% at 24 months, relative to resistance in AL rats. Results also suggest that resistance to both AAPH and AMVN was decreased slightly in older AL rats, but was maintained in the DR rats. These results show that DR augments the defense systems that protect one of the mitochondria's most vulnerable systems. This augmentation is one of the largest magnitude effects of DR yet observed against oxidative challenge.