Caloric restriction and melatonin substitution: effects on murine circadian parameters

Aging effects have been reported in endocrine, metabolic and behavioral circadian rhythms. The effects of age on the circadian system have been investigated primarily in rats and hamsters and only seldom in mice. Our aim was to assess the effects of two common "anti-aging" treatments, namely caloric restriction (CR) and melatonin substitution, on the circadian system of mice. Animals were subjected to phase delays of the light-dark cycle and constant darkness (DD). The most pronounced change in the murine circadian system was the length of the endogenous period, tau, which increased with age regardless of treatment. CR had diverse effects e.g., enabling a more rapid phase shift response while concomitantly leading to a fragmented circadian phenotype with considerable activity during the rest (light) phase. Melatonin enforced the adaptation to the light/dark cycle, thus facilitating a rapid re-entrainment to phase delayed lighting conditions. Interestingly, the melatonin-substituted animals displayed an increase in locomotor activity under constant darkness and in 50% of all cases a biphasic (split) activity pattern. These results contribute to the phenotypic evaluation of two very different approaches to intervene in the age-related degeneration of the mammalian circadian system. As both CR and melatonin have negative and positive effects on the behavioral expression of clock function (i.e., fragmentation of rhythms vs. faster re-entrainment), their usefulness in managing age-related circadian disorders may be limited.