Abstract

Aging has significant effects on circadian behavior across a wide variety of species, but the underlying mechanisms are poorly understood. Previous work has demonstrated the age-dependent decline in behavioral output in the model organism Drosophila. We demonstrate that this age-dependent decline in circadian output is combined with changes in daily activity of Drosophila. Aging also has a large impact on sleep behavior, significantly increasing sleep duration while reducing latency. We used electrophysiology to record from large ventral lateral neurons of the Drosophila circadian clock, finding a significant decrease in input resistance with age but no significant changes in spontaneous electrical activity or membrane potential. We propose this change contributes to observed behavioral and sleep changes in light-dark conditions. We also demonstrate a reduction in the daily plasticity of the architecture of the small ventral lateral neurons, likely underlying the reduction in circadian rhythmicity during aging. These results provide further insights into the effect of aging on circadian biology, demonstrating age-related changes in electrical activity in conjunction with the decline in behavioral outputs.

Highlights

  • Circadian rhythms describe the near 24-hour cycle in behavior and physiology, driven by the circadian clock, which allow organisms to anticipate daily changes in their environment

  • Aging caused a weakening in circadian behavioral output and lengthening of the free-running period

  • In agreement with previously reported work (Rakshit et al, 2012; Umezaki et al, 2012), we found that aging resulted in a significant decline in the strength of circadian locomotor activity under free-running conditions (Fig. 1B, p 1⁄4 0.0001, Kruskal-Wallis statistic 1⁄4 27.17), with a steep decline in flies aged 36 days and older and a significant lengthening of the period of the observed behavioral activity (Fig. 1C, p < 0.0001, Kruskal-Wallis statistic 1⁄4 95.3)

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Summary

Introduction

Circadian rhythms describe the near 24-hour cycle in behavior and physiology, driven by the circadian clock, which allow organisms to anticipate daily changes in their environment. Circadian clocks in animals are fundamental biological components responsible for the control of large aspects of physiology and behavior, ranging from the sleep-wake cycle to rhythms in blood pressure (Roenneberg and Merrow, 2016). The daily cycles of hormone levels, body temperature, and the sleep-wake cycle are modified with age in humans, causing disruption in behavior and resultant reduction in the strength of the clock (Hofman and Swaab, 2006). Circadian sleep-wake disorders are more prevalent in older individuals (Kim and Duffy, 2018)

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