Robust biological rhythms have been shown to affect life span. Biological clocks can be entrained by two feeding regimens, restricted feeding (RF) and caloric restriction (CR). RF restricts the time of food availability, whereas CR restricts the amount of calories with temporal food consumption. CR is known to retard aging and extend life span of animals via yet unknown pathways. We hypothesize that resetting the biological clock could be one possible mechanism by which CR extends life span. As it is experimentally difficult to uncouple calorie reduction from temporal food consumption, we took advantage of the transgenic mice MUPA overexpressing a serine protease implicated in brain development and plasticity that exhibit spontaneously reduced eating and increased life span. Quantitative real-time PCR analysis revealed that MUPA mice exhibit robust expression of the clock genes mPer1, mPer2, mClock, and mCry1, but not mBmal1 in the liver. We also found changes in the circadian amplitude and/or phase of clock-controlled output systems, such as feeding behavior, body temperature, and enteric cryptdin expression. A change in the light/dark regimen led to modified clock gene expression and abrogated circadian patterns of food intake in WT and MUPA mice. Consequently, food consumption of WT mice increased whereas that of MUPA remained the same, indicating that reduced food intake occurs upstream and independently of the biological clock. Thus, we surmise that CR could lead to pronounced and synchronized biological rhythms. As the biological clock controls mitochondrial, hormonal, and physiological parameters, system synchronicity could lead to extended life span.