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The circadian clock, aging and its implications in cancer.
Circadian clock orchestrates the intergenic biochemical, physiological and behavioral changes to form an approximate 24h oscillation through the transcription-translation feedback loop (TTFL). Mechanistically, a heterodimer of transcriptional activator formed by BMAL1 and CLOCK, governs the expression of its transcriptional repressors, CRY, PER and REV-ERBα/β proteins, thereby controlling more than 50 % of protein encoding genes in human. There is also increasing evidence showing that tumor microenvironment can disrupt specific clock gene functions to facilitate tumorigenesis. Although there is great progress in understanding the molecular mechanisms of the circadian clock, aging and cancer, elucidating their complex relationships among these processes remains challenging. Herein, the optimization of the chronochemotherapy regimen has not been justified yet for treatment of cancer. Here, we discuss the hypothesis of relocalization of chromatin modifiers (RCM) along with function(s) of the circadian rhythm on aging and carcinogenesis. We will also introduce the function of the chromatin remodeling as a new avenue for rejuvenation of competent tissues to combat aging and cancer.
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