Genetic Defects of the Mammalian Circadian clock and Pre

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DESCRIPTION (provided by applicant): A large body of information has indicated that the physiology and behavior of living organisms from bacteria to humans are controlled by circadian rhythms driven by endogenous oscillators in response to daily environmental cues. The first gene encoding a molecular player of the circadian clock, period (per) was identified in Drosophila. My laboratory was instrumental in the identification of two mammalian period homologue, mPerl and mPer2. We have recently provided genetic evidences that mPerl and mPer2 are indeed key players in the control of the circadian. Loss of function mutation of mPer2 gene results in the loss in control of circadian rhythmicity. The loss of mPerl gene affects the precision control of the clock period but the mutant animals retained circadian rhythmicity. However, a loss of both mPerl and mPer2 results in a complete absence of circadian clock activity. An interesting observation of these clock defective animals, especially those with mPer2 mutation is that they apparently age prematurely. In this proposal, we would like to test the hypothesis that the circadian clock is an overt clock involved in aging. Specifically we would like to understand circadian clock control of mitochondria homeostasis.