Age-Induced Differential Changes in the Central and Colonic Human Circadian Oscillators

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.

Effects of resveratrol on in vitro circadian clock gene expression in young and older human adipose-derived progenitor cells

“…Differences in gene expression levels across ages have been previously reported in other tissues [27,28]. For example, human colon tissue from participant donors over 74 yrs exhibits increased CLOCK, PER2, and BMAL1 expression, compared to colon tissue from younger participants [27]. Similarly, rat liver tissue from middle-aged animals exhibits increased NR1D1 and NR1D2 expression, compared to rat liver tissue from young [28].…”

“…Although the circadian rhythmicity patterns measured in vitro were consistent between young and older preadipocytes, we observed increased expression levels of CLOCK, PER2, NR1D1 in older-APCs compared to young-APCs. Differences in gene expression levels across ages have been previously reported in other tissues [27,28]. For example, human colon tissue from participant donors over 74 yrs exhibits increased CLOCK, PER2, and BMAL1 expression, compared to colon tissue from younger participants [27].…”

Does enteral nutrition require continuity of management: A randomized controlled study

“…For ICU patients, continuous day and night nutrition pumping can increase the body’s tolerance to treatment, but at the same time, it also directly leads to the secretion cycle disorder of bile acid, insulin, ghrelin, and other digestive hormones 21 , 22 , resulting in patients with varying degrees of digestive system symptoms during the withdrawal stage of tube feeding. In addition, the continuous pumping of nutrients in the course of enteral nutrition therapy will keep the satiety center of the body in an excited state, resulting in different degrees of anorexia, poor appetite, and other symptoms in the withdrawal stage of tube feeding 23 .…”

Special Issue “Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration”

“…The molecular mechanisms underlying tissue homeostatic failure during aging will make them more prone to degeneration. In this Special Issue, Camello-Almaraz et al [ 6 ] point out that aging not only modifies multiple cellular and homeostatic systems but also biological rhythms. Ambulatory recordings of the circadian rhythms of skin wrist temperature, motor activity, and the integrated variable temperature, activity, and position were dampened by aging, especially beyond 74 years of age.…”