The functional changes of the circadian system organization in aging

Zhao, Jia; Warman, Guy R.; Cheeseman, James F.

doi:10.1016/j.arr.2019.04.006

Cited by 37 publications

(27 citation statements)

References 139 publications

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“…We describe here an increase in the amplitude of human peripheral clock genes, a novel finding to our knowledge. A previous study in mouse reported no effects of aging in the expression of clock genes in colon and small intestine [23], in line with most of evidences from other tissues [13].…”

Section: Discussionsupporting

confidence: 79%

“…Aging also alters glucocorticoid levels, which have been reported to entrain gut clock genes [29]. This would be also 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]), although chronodisruption induced by external conditions alters the molecular clocks of colon and other gastrointestinal organs in rat [30,31].…”

Section: Discussionsupporting

confidence: 65%

“…Some studies have reported a disorganization of central circadian rhythms such as body temperature or sleep [10][11][12]. By the contrary, information about the effect of aging on clock genes is relatively scarce and non-conclusive: both impairment and change have been reported for clock gene expression in SCN of animal models [13], while there is no information in the human species.…”

Section: Of 13mentioning

confidence: 99%

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

Camello-Almaraz

Martín-Cano

Santos³

et al. 2020

IJMS

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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.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 65%

Section: Of 13mentioning

confidence: 99%

See 1 more Smart Citation

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

Camello-Almaraz

Martín-Cano

Santos³

et al. 2020

IJMS

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“…Remarkably, functional deterioration of an SCN during aging greatly reduces longevity, while transplanting the SCN from young donors into old hamsters increases their lifespan by almost 20% [14]. Core clock gene expression in the SCN is affected during aging in a gene-specific manner and aged SCN neurons have reduced circadian amplitude of intracellular signaling [15]. These likely contribute to the aging-related dampening of the circadian SCN-dependent output.…”

Section: The Aged Circadian Clock Networkmentioning

confidence: 99%

Elderly as a High-risk Group during COVID-19 Pandemic: Effect of Circadian Misalignment, Sleep Dysregulation and Melatonin Administration

et al. 2020

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The association of age with a higher vulnerability to COVID-19 infection is a subject of major importance. Several factors, including higher stress due to social isolation, diminished melatonin levels with age, and higher exposure of individuals to light at the evening, which reduces melatonin levels and disrupts circadian rhythmicity are relevant for maintaining the circadian health in aged individuals. Properly administered, chronotherapy restores the optimal circadian pattern of the sleep-wake cycle in the elderly. It involves adequate sleep hygiene, timed light exposure, and the use of a chronobiotic medication like melatonin, which affects the output phase of circadian rhythms thus controlling the biological clock. Besides, the therapeutic potential of melatonin as an agent to counteract the consequences of COVID-19 infections has been advocated due to its wide-ranging effects as an antioxidant, anti-inflammatory, and as an immunomodulatory agent, as well as to a possible antiviral action. This article discusses how chronotherapy may reverse the detrimental circadian condition of the elderly in the COVID-19 pandemic.

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“…What is generally accepted, is that aging affects the entrainment of the central clock in various ways, and that dyssynchrony in the central clock can cause dysregulations in the peripheral clocks [31]. What is still under debate, however, is if peripheral clocks are individually affected upon aging, given that many age-induced effects appear to be tissue-specific [30]. In this study, we provide a global analysis of lipid species in WAT and BAT around the clock, in young and old mice.…”

Section: Discussionmentioning

confidence: 99%

Aging selectively dampens oscillation of lipid abundance in white and brown adipose tissue

Held

Buijink

Elfrink

et al. 2020

Preprint

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Lipid metabolism is under the control of the circadian system and circadian dysregulation has been linked to obesity and dyslipidemia. These factors and outcomes have also been associated to, or affected by, the process of aging. Here, we investigated whether murine white (WAT) and brown (BAT) adipose tissue lipids exhibit rhythmicity and if this is affected by aging. To this end, we have measured the 24 hour lipid profiles of WAT and BAT using a global lipidomics analysis of >1100 lipids. We observed rhythmicity in nearly all lipid classes including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. Overall, ~22% of the analyzed lipids were considered rhythmic in WAT and BAT. Despite a general accumulation of lipids upon aging the fraction of oscillating lipids decreased in both tissues to 14% and 18%, respectively. Diurnal profiles of lipids in BAT appeared to depend on the lipid acyl chain length and this specific regulation was lost in aged mice. Our study revealed how aging affects the rhythmicity of lipid metabolism and could contribute to the quest for targets that improve diurnal lipid homeostasis to maintain cardiometabolic health during aging.

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The functional changes of the circadian system organization in aging

Cited by 37 publications

References 139 publications

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

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

Elderly as a High-risk Group during COVID-19 Pandemic: Effect of Circadian Misalignment, Sleep Dysregulation and Melatonin Administration

Aging selectively dampens oscillation of lipid abundance in white and brown adipose tissue

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