Abstract
Aging modifies not only multiple cellular and homeostatic systems, but also biological rhythms. The circadian system is driven by a central hypothalamic oscillator which entrains peripheral oscillators, in both cases underlain by circadian genes. Our aim was to characterize the effect of aging in the circadian expression of clock genes in the human colon. Ambulatory recordings of the circadian rhythms of skin wrist temperature, motor activity and the integrated variable TAP (temperature, activity and position) were dampened by aging, especially beyond 74 years of age. On the contrary, quantitative analysis of genes expression in the muscle layer of colonic explants during 24 h revealed that the circadian expression of Bmal1, Per1 and Clock genes, was larger beyond that age. In vitro experiments showed that aging induced a parallel increase in the myogenic contractility of the circular colonic muscle. This effect was not accompanied by enhancement of Ca2+ signals. In conclusion, we describe here for the first time the presence of a molecular oscillator in the human colon. Aging has a differential effect on the systemic circadian rhythms, that are impaired by aging, and the colonic oscillator, that is strengthened in parallel with the myogenic contractility.
Highlights
Aging is a complex and multifactorial process which involves a large number of structural and functional alterations from the cellular to the homeostatic levels [1]
The circadian system is composed by a central pacemaker located at the suprachiasmatic nuclei (SCN) of the hypothalamus and the oscillators present at peripheral tissues
Environmental cues such as light-dark cycle entrain the SCN, which operates as central pacemaker and sets in phase the peripheral oscillators [3]
Summary
Aging is a complex and multifactorial process which involves a large number of structural and functional alterations from the cellular to the homeostatic levels [1]. Bey. tBhyetchoenctroanrtyra, wryr, iwstrtiesmt tpemerpaeturareture shoswhoswans aonppoopspitoesibteehbaevhiaovr,iodrr,odprpopinpginagftearftwerawkiankgintigmteim, we,hwilehiilterietmreaminasinatshaitghhiegshtelsetvleelvdeul rdiunrginthgethe night This two-levels switching behavior is a known feature of some human circadian rhythms and in clock genes of gastrointestinal tract [15], so that for quantification the non-parametric circadian. Aging alters glucocorticoid levels, which have been reported to entrain gut clock genes [29] This would be in keeping with the finding that peripheral oscillators are less sensitive than the central oscillator to changes in external time-setting stimuli (reviewed in [13]), chronodisruption induced by external conditions alters the molecular clocks of colon and other gastrointestinal organs in rat [30,31]. This means that the target is another component of the contractile pathway, such as the contractile proteins or the Ca2+ sensitizing pathways
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