Long‐lived and Obesity Resistant Mice Exhibit 24 h Locomotor Circadian Rhythms at Young and Old Age

Abstract

Ageing is associated with disruption of circadian homeostasis, including reduced entraiment to light‐dark cycles, reduced amplitude and desynchronization of circadian physiological rhythms, and shortening or lengthening of the endogenous circadian period length (tau). αMUPA mice carry a transgene encoding the urokinase‐type plasminogen activator, an extracellular protease implicated in fibrinolysis, tissue remodeling, and brain plasticity. Female αMUPA mice spontaneously eat ~25% less, live ~20% longer, and show high‐amplitude circadian rhythms in food intake, body temperature, and in hepatic clock gene expression levels, compared with WT mice. Herein we examined the tau of locomotor activity of mature (8‐month old) and aged (18‐month old) female αMUPA and WT mice under total darkness. We show that tau changed in WT mice from a period <24 h at 8 months to a period >;24 h at 18 months. However, tau of αMUPA mice was ~24 h at both ages. Deviation of tau from 24 h has shown to be inversely related to life span of rodents and nonhuman primates. Hence, our results suggest that the sustainable endogenous period of ~24 h in αMUPA mice may contribute to their longevity. These results support the hypothesis that although a non‐24‐h tau has an adaptive significance in allowing a better response to natural daylight changes, such a lack of resonance between tau and external period length entails a life‐shortening metabolic cost.