The response to calorie restriction in mammals shows features also common to hibernation: a cross-adaptation hypothesis.

The marked elevation in hepatic carbamyl phosphate synthetase I (CPSI) in calorie-restricted mice, and the changes in erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and in hemoglobin oxygen affinity in calorie-restricted and hypoxic humans living in Biosphere 2 suggest similarities between physiologic events in calorie restriction and hibernation. Other data from the literature strengthen this comparison. Accordingly, we hypothesize that the response to the calorie restriction regime as studied by gerontologists, rather than being a laboratory artifact, is part of a spectrum of responses to food deprivation which have adaptive value in the wild, and whose triggering mechanism may primarily involve the neuroendocrine system.