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P A Y W A L L E D S O U R C E : Mechanisms of Aging and Development
Highlights
• Circadian expression of intestinal cell cycle genes was silenced during aging.
• Circadian expression of intestinal clock genes was mostly unaffected by aging.
• Tumorigenesis silenced or dumped circadian rhythmicity of intestinal clock genes.
• Tumorigenesis does not affect coupling of circadian clock and cell cycle.
Abstract
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.
Outline
1. Introduction
2. Materials and methods
2.1. Animals and treatments
2.2. Real-time quantitative RT-PCR
2.3. Plasma corticosterone determination
2.4. Statistical analysis
3. Results
3.1. Daily rhythm of corticosterone
3.2. Expression of circadian clock and clock-controlled genes
3.3. Daily rhythms of the cell cycle genes
3.4. Daily rhythms of oncogenic proliferation-associated genes
4. Discussion
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