Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature Aging.

Alexander Stankiewicz,Lili Yu,Erin Mcgowan,Irina Zhdanova

doi:10.3390/ijms18112243

Alexander Stankiewicz, Lili Yu + Show 2 more

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https://doi.org/10.3390/ijms18112243

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Abstract

Chronic high caloric intake (HCI) is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior. A remarkable decline in adult neurogenesis in 1-year old HCI animals, amounting to only 21% of that in age-matched Control, exceeds age-dependent decline observed in normal 3-year old zebrafish. This is associated with misalignment or reduced amplitude of daily patterns for principal cell cycle regulators, cyclins A and B, and p20, in brain tissue. Together, these data establish HCI in zebrafish as a model for metabolically induced premature aging of sleep, circadian functions, and adult neurogenesis, allowing for a high throughput approach to mechanistic studies and drug trials in a diurnal vertebrate.

Highlights

High caloric intake (HCI) can result from an overall increase in the amount of food consumed or excess of high-calorie ingredients in dietary products, sugars, or fats
We find that aging zebrafish show a progressive reduction in locomotor activity, an increase in anxiety-like behaviors [48], a decline in circadian rhythmicity, and spatial memory [49]
We show that, in zebrafish, chronic caloric excess from early age leads to premature aging reflected in multiple abnormalities, from anatomical deformities to early onset of anxiety-like behavior, altered sleep, reduced amplitude of circadian rhythms, and a remarkable decline in adult neurogenesis

Summary

Introduction

High caloric intake (HCI) can result from an overall increase in the amount of food consumed or excess of high-calorie ingredients in dietary products, sugars, or fats. Accumulation of excessive body fat with its powerful energy-generating and endocrine effects, altered liver metabolism, cholesterol imbalance, and other effects of HCI are implicated in the development of metabolic syndrome, type 2 diabetes, and cardiovascular disorders [1,2,3,4]. These metabolic changes constitute a high risk for sleep disorders, including insomnia and sleep apnea, and is associated with circadian rhythm abnormalities [5,6]. Caloric restriction is found to slow down aging, increase lifespan, and counteract age-related diseases [7,8,9,10]

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