Food, sex and time are the three most important variables in the life of any organism, especially mammals. Food provides the energy for somatic growth and reproduction, while light-dark cues organize daily and seasonal patterns of feeding, breeding, metabolism and activity. Even in humans, proper light/dark cues are essential for maintaining circadian rhythms. In fact, the disruption of biological rhythms, whether ultradian, circadian, or infradian, may be related to a wide range of psychiatric and somatic pathophysiologies, especially in females, where the interaction of light and food is critical to regular ovulation. This interaction is easily studied in small mammals who typically exhibit a 4-6 day estrous cycle- both proper time cues and correct nutrition are necessary for ovulation and behavioral estrum. House mice (Mus musculus) are excellent models for studying fertility and sex differences. Thus, the first goal of this proposal is to establish a unique research program to study how circadian rhythms act as permissive organizing forces in the complete life cycle of a small mammal, particular in relation to puberty, reproduction and senescence. A second research goal is to study the relationship between circadian rhythms and food energy to understand how these interacting factors impinge on growth and aging within both sexes. Furthermore, since regular ovulation is the best indicator of somatic and reproductive health in a female mammal, changes in the estrous cycle and, hence, the frequency of ovulation will be a key measurement here. The chronology of growth, development, reproduction and senescence in male and female house mice, from conception to death, will be investigated at these conditions: 1) at non-24 hour days (tau-cycles) in which the circadian clock is either entrained to extreme 21 hour of 27 hour days, or disrupted by non- entrainable 19 hour light/dark cycles; 2) at high versus low fat diets; and, 3) in a caging system where animals are challenged to work for their food calories by exercising on a running wheel. The results of each experiment will suggest which interactions among food, sex, and circadian time have the most influence on health and longevity.
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