Aging and tumorigenesis are associated with decline and disruption of circadian rhythms in many tissues and accumulating evidence indicates molecular link between circadian clock and cell cycle. The aim of this study was to investigate the effect of aging and tumorigenesis on coupling between cell cycle and circadian clock oscillators in colon, which undergoes regular rhythmicity of cell cycle and expresses peripheral circadian clock. Using healthy 14-week-old mice and 33-week-old mice with and without colorectal tumors, we showed that the 24-h expression profiles of clock genes and clock-controlled genes were mostly unaffected by aging, whereas the genes of cell cycle and cell proliferation were rhythmic in the young colons but were silenced during aging. On the other hand, tumorigenesis completely silenced or dampened the circadian rhythmicity of the clock genes but only a few genes associated with cell cycle progression and cell proliferation. These results suggest that aging impacts the colonic circadian clock moderately but markedly suppresses the rhythms of cell cycle genes and appears to uncouple the cell cycle machinery from circadian clock control. Conversely, tumorigenesis predominantly affects the rhythms of colonic circadian clocks but is not associated with uncoupling of circadian clock and cell cycle.

衰老和肿瘤发生与许多组织中昼夜节律的下降和破坏有关，越来越多的证据表明生物钟和细胞周期之间存在分子联系。本研究的目的是研究衰老和肿瘤发生对结肠细胞周期和生物钟振荡器耦合的影响，结肠细胞周期有规律的节律并表达外周生物钟。使用健康的 14 周龄小鼠和 33 周龄小鼠有或没有结直肠肿瘤，我们发现时钟基因和时钟控制基因的 24 小时表达谱大多不受衰老影响，而细胞周期基因和细胞增殖在年轻的结肠中是有节奏的，但在衰老过程中被抑制了。另一方面，肿瘤发生完全沉默或抑制了时钟基因的昼夜节律性，但只有少数与细胞周期进程和细胞增殖相关的基因。这些结果表明，衰老适度影响结肠生物钟，但显着抑制细胞周期基因的节律，似乎使细胞周期机制与生物钟控制脱钩。相反，肿瘤发生主要影响结肠生物钟的节律，但与生物钟和细胞周期的解偶联无关。这些结果表明，衰老适度影响结肠生物钟，但显着抑制细胞周期基因的节律，似乎使细胞周期机制与生物钟控制脱钩。相反，肿瘤发生主要影响结肠生物钟的节律，但与生物钟和细胞周期的解偶联无关。这些结果表明，衰老适度影响结肠生物钟，但显着抑制细胞周期基因的节律，似乎使细胞周期机制与生物钟控制脱钩。相反，肿瘤发生主要影响结肠生物钟的节律，但与生物钟和细胞周期的解偶联无关。