Effects of age on circadian rhythms are similar in wild-type and heterozygous Clock mutant mice

The amplitudes of many circadian rhythms, at the behavioral, physiological, cellular, and biochemical levels, decrease with advanced age. Previous studies suggest that the amplitude of the central circadian pacemaker is decreased in old animals. Recently it has been reported that expression of several circadian clock genes, including Clock, is lower in the master circadian pacemaker of old rodents. To test the hypothesis that decreased activity of a circadian clock gene renders animals more susceptible to the effects of aging, we analyzed the circadian rhythm of locomotor activity in young and old wild-type and heterozygous Clock mutant mice. We found that the effects of age and the Clock mutation were additive. These results indicate that age-related changes in circadian rhythmicity occur equally in wild-type and heterozygous Clock mutants, suggesting that the Clock mutation does not render mice more susceptible to the effects of age on the circadian pacemaker. 0 2003 Elsevier Inc. All rights reserved.