The influence of acute, late-life calorie restriction on whole body energy metabolism in p66Shc(-/-) mice.

It has been proposed that Shc proteins may influence aging by regulating insulin signaling and energy metabolism. Evidence suggests that deletion of p66Shc could partially attenuate weight gain on a high fat diet by increasing energy expenditure. However, the impact of p66Shc on the metabolic response to calorie restriction (CR) has not been determined. Thus, we used indirect respiration calorimetry to determine the impact of CR on energy expenditure (EE) and substrate utilization (RQ) in 18mo p66Shc(-/-) and wild-type (WT) mice. Calorimetry measurements were completed at baseline and following 3d of 40% CR and 2 mo of 26% CR. There was no difference (P>0.10) in EE and RQ between gentoypes, regardless of how EE data was normalized. Both p66Shc(-/-) and WT mice showed decreases (P<0.001) in EE normalized for body weight at 2 mo of CR. However, the response to 3d of CR was different between genotypes with only the p66Shc(-/-) showing a decrease (P<0.001) in 24 h EE expressed per mouse or normalized for body weight. The results indicate that p66Shc does not significantly influence EE in 18 mo mice at baseline or 2 mo of CR, although it may play a role in the EE response to very acute CR.