There has been substantial recent interest in the possible role of oxidative stress as a mechanism underlying life-history trade-offs, particularly with regard to reproductive costs. Several recent papers have found no evidence that reproduction increases oxidative damage and so have questioned the basis of the hypothesis that oxidative damage mediates the reproduction-lifespan trade-off. However, we suggest here that the absence of the predicted relationships could be due to a fundamental problem in the design of all of the published empirical studies, namely a failure to manipulate reproductive effort. We conclude by suggesting experimental approaches that might provide a more conclusive test of the hypothesis.
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