Accumulated oxidative stress resulting from a gradual shift in the redox status of tissues is now considered to be a key mechanism underlying the aging process. Calorie‐restricted (CR) feeding, an experimental protocol to extend survival and delay aging in rodents, is recognized to slow the rate of accrual of age‐related oxidative stress. This conclusion is based on the increase in tissues with age of the oxidation products of proteins, lipids and DNA. The functional consequence, however, of the accumulation of these non‐specific oxidative markers is more difficult to determine. A shift in the redox status of tissues with age and calorie restriction feeding may have a greater impact on cell function through activation of redox sensitive transcription factors than through the accumulation of these non‐specific oxidative markers. Activation of such transcription factors will stimulate signalling pathways that will lead to a change in the gene expression profile and cell functioning. Little research has been conducted in this area. It has been proposed that CR feeding slows the rate of accrual of oxidative damage because mitochondria in these animals have a lower rate of superoxide generation when compared with mitochondria from control animals. This proposal is based on in vitro observations using isolated mitochondria and clearly requires further confirmation in isolated cells or using an in vivo approach. The application of metabolic control analysis to identify in isolated mitochondria the mechanism underlying this response has suggested one possible explanation for the lower superoxide production rates observed.