Aging-induced alterations in female rat colon smooth muscle: the protective effects of hormonal therapy

Pascua, Patricia; Camello-Almaraz, Cristina; Pozo, Marı́a J.; Martín-Cano, Francisco E.; Vara, Elena; Fernández-Tresguerres, Jesús Ángel; Camello, Pedro J.

doi:10.1007/s13105-011-0138-7

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…Some data suggest that the origin of these functional changes could be the impairment of the Ca 2+ signals and other intracellular routes controlling the contractile proteins [reviewed in ]. In addition, the mitochondrial potential was altered in colonic smooth muscle cells from aged rat , and we have shown changes in the oxidative and apoptotic parameters of aged rat colonic muscle . These changes were inhibited by melatonin.…”

Section: Introductionmentioning

confidence: 69%

Age‐related changes in mitochondrial function of mouse colonic smooth muscle: beneficial effects of melatonin

Martín-Cano

Camello-Almaraz

Acuña-Castroviejo

et al. 2013

Journal of Pineal Research

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Aging is a multifactorial process that involves biochemical, structural, and functional changes in mitochondria. The ability of melatonin to palliate the alterations induced by aging is based on its chronobiologic, antioxidant, and mitochondrial effects. There is little information about the effects of melatonin on the in situ mitochondrial network of aging cells and its physiological implications. We have studied the ability of melatonin to prevent the functional alterations of in situ mitochondria of smooth muscle cells and its impact on contractility. Mitochondrial membrane potential was recorded in isolated colonic smooth muscle cells from young mice (3 month old), aged mice (22-24-month old), and aged mice treated with melatonin (starting at 14-month age). Aging induced a partial mitochondrial depolarization in resting conditions and reduced the depolarizing response to cellular stimulation. Use of oligomycin indicated that aging enhanced the resting activity of the mitochondrial ATP synthase, whereas in young cells, the enzyme operated mainly in reverse mode. Melatonin treatment prevented all these changes. Aging reduced both spontaneous and stimulated contraction of colonic strips and shifted the metabolic dependence of contraction from mitochondria to glycolysis, as indicated the use of mitochondrial and glycolysis inhibitors. These functional alterations were also palliated by melatonin treatment. Aging effects were not related to a decrease in Ca2+ store mobilization, because this was enhanced in aged cells and restored by melatonin. In conclusion, melatonin prevents the age induced in situ mitochondrial potential alterations in smooth muscle cells and the associated changes in contractility and metabolism.

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Section: Introductionmentioning

confidence: 69%

Age‐related changes in mitochondrial function of mouse colonic smooth muscle: beneficial effects of melatonin

Martín-Cano

Camello-Almaraz

Acuña-Castroviejo

et al. 2013

Journal of Pineal Research

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“…This manifests in a shift towards oxidative mechanisms and a decline in the efficiency of the proteasome, thus the aging organism will be less resistant to stress conditions and to several diseases [30]. It is demonstrated that the aging process affects the GI tract, which is supported by the following signs and symptoms: delayed transit time, constipation, neuronal loss, and general low-grade chronic inflammation, but the underlying mechanisms are not well elucidated [31,32]. It is well-known that due to the presence of different gonadal hormones, there are predisposition differences between males and females in the aging process.…”

Section: Discussionmentioning

confidence: 99%

Effects of aging on proteasomal-ubiquitin system, oxidative stress balance and calcium homeostasis in middle-aged female rat colon

Almási

Murlasits

Al-awar

et al. 2021

PhysInt

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Aging is a multifactorial process, which is considered as a decline over time. It is increasingly clear that there is a gender difference in aging and in the prevalence of age-related diseases as well. We aimed to examine the effects of the aging process in the colonic tissue of female Wistar rats aged 10 weeks (young) and 13 months (middle-aged) at an early stage, according to three main symptoms associated with aging: a decrease in the efficacy of the proteasome and muscle function and an increase in oxidative stress. The aging process was found to cause a significant decrease in ubiquitin C-terminal hydrolase ligase (UCHL-1) and a significant increase in 3-nitrotyrosine (3-NT), total glutathione (GSH), calcium (Ca2+), calcitonin gene-related peptide (CGRP) and superoxide dismutase (SOD) activity in middle-aged animals. In summary, it is suggested that the reduced activity of the proteasomal degradation system may be the result of the diminished expression of the UCHL-1 enzyme and the decreased levels of ubiquitin; furthermore, we found some key targets which may help to better understand the fundamental aging process.

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“…26 MEL treatment can also reverse age-related increases in mucosal 5-HT availability 27 and markers of inflammation in mouse colon. 28 Taken together, these studies suggest that MEL may be antiaging both at the organismal level and also at the level of individual tissues. Therefore, understanding the changes in MEL levels with age may provide insight into the decline in colonic function.…”

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confidence: 87%

Age-Related Changes in Melatonin Release in the Murine Distal Colon

Diss

Robinson

et al. 2013

ACS Chem. Neurosci.

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Constipation and fecal impaction are conditions of the bowel whose prevalence increases with age. Limited information is known about how these conditions manifest; however, functional deficits are likely to be due to changes in signaling within the bowel. This study investigated the effects of age on colonic mucosal melatonin (MEL) release and the consequences this had on colonic motility. Electrochemical measurements of MEL overflow demonstrated that both basal and mechanically stimulated MEL release decreased with age. The MEL/serotonin also decreased with increasing age, and the trend was similar to that of MEL overflow, suggestive that age-related changes were primarily due to a reduction in MEL levels. Levels of N-acetylserotonin and the N-acetylserotonin/serotonin ratio were reduced with age, providing an explanation for the reduction in MEL release. Decreases in colonic motility were observed in animals between 3 and 24 months old. Exogenous application of MEL could reverse this deficit in aged colon. In summary, we propose that the age-related decline in MEL release may be due to either decreases or alterations in mechanosensory channels and/or a loss in levels/activity of the N-acetyltransferase enzyme responsible for the synthesis of N-acetylserotonin. Decreases in MEL release may explain the decreases in colonic motility observed in 24 month old animals and could offer a new potential therapeutic treatment for agerelated constipation.

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Aging-induced alterations in female rat colon smooth muscle: the protective effects of hormonal therapy

Cited by 5 publications

References 39 publications

Age‐related changes in mitochondrial function of mouse colonic smooth muscle: beneficial effects of melatonin

Age‐related changes in mitochondrial function of mouse colonic smooth muscle: beneficial effects of melatonin

Effects of aging on proteasomal-ubiquitin system, oxidative stress balance and calcium homeostasis in middle-aged female rat colon

Age-Related Changes in Melatonin Release in the Murine Distal Colon

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