DIETARY RESTRICTION AUGMENTS RESISTANCE TO OXIDANT-MEDIATED INHIBITION OF MITOCHONDRIAL TRANSCRIPTION

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