Human circadian phase-response curves for exercise.

Shawn D Youngstedt,Jeffrey A Elliott,Daniel F Kripke

doi:10.1113/jp276943

Shawn D Youngstedt, Jeffrey A Elliott + Show 1 more

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https://doi.org/10.1113/jp276943

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Abstract

Key points Exercise elicits circadian phase‐shifting effects, but additional information is needed.The phase–response curve describing the magnitude and direction of circadian rhythm phase shifts, depending on the time of the zeigeber (time cue) stimulus, is the most fundamental chronobiological tool for alleviating circadian misalignment and related morbidity.Fifty‐one older and 48 young adults followed a circadian rhythms measurement protocol for up to 5.5 days, and performed 1 h of moderate treadmill exercise for 3 consecutive days at one of eight times of the day/night.Temporal changes in the phase of 6‐sulphatoxymelatonin (aMT6s) were measured from evening onset, cosine acrophase, morning offset and duration of excretion. Significant phase–response curves were established for aMT6 onset and acrophase with large phase delays from 7:00 pm to 10:00 pm and large phase advances at both 7:00 am and from 1:00 pm to 4:00 pm. Delays or advances would be desired, for example, for adjustment to westward or eastward air travel, respectively.Along with known synergism with bright light, the above PRCs with a second phase advance region (afternoon) could support both practical and clinical applications. Although bright light is regarded as the primary circadian zeitgeber, its limitations support exploring alternative zeitgebers. Exercise elicits significant circadian phase‐shifting effects, but fundamental information regarding these effects is needed. The primary aim of the present study was to establish phase–response curves (PRCs) documenting the size and direction of phase shifts in relation to the circadian time of exercise. Aerobically fit older (n = 51; 59–75 years) and young adults (n = 48; 18–30 years) followed a 90 min laboratory ultrashort sleep–wake cycle (60 min wake/30 min sleep) for up to 5½ days. At the same clock time on three consecutive days, each participant performed 60 min of moderate treadmill exercise (65–75% of heart rate reserve) at one of eight times of day/night. To describe PRCs, phase shifts were measured for the cosine‐fitted acrophase of urinary 6‐sulphatoxymelatonin (aMT6s), as well as for the evening rise, morning decline and change in duration of aMT6s excretion. Significant PRCs were found for aMT6s acrophase, onset and duration, with peak phase advances corresponding to clock times of 7:00 am and from 1:00 pm to 4:00 pm, delays from 7:00 pm to 10:00 pm, and minimal shifts around 4:00 pm and 2:00 am. There were no significant age or sex differences. The amplitudes of the aMT6s onset and acrophase PRCs are comparable to expectations for bright light of equal duration. The phase advance to afternoon exercise and the exercise‐induced PRC for change in aMT6s duration are novel findings. The results support further research exploring additive phase‐shifting effects of bright light and exercise and health benefits.

Highlights

Under usual conditions, exposure to light and other zeitgebers entrains the circadian system to the earth’s 24 h rotation to promote a species-specific temporal and environmental niche (Johnson et al, 2003)
The timings of the morning phase advance and evening–night phase delay regions of the exercise phase–response curves (PRCs) are similar to the bright light PRC that we found using the same protocol (Kripke et al 2007)
Not statistically different by ANOVA, the individual PRCs of older adults can be expected to be functionally earlier compared to young adults because three of our studies have shown that baseline aMT6s onset and acrophase were significantly earlier in the older subjects (Kripke et al, 2003, 2007) and the present study (Table 1)

Summary

Introduction

Exposure to light and other zeitgebers (time cues) entrains the circadian system to the earth’s 24 h rotation to promote a species-specific temporal and environmental niche (Johnson et al, 2003). In modern society, misalignment between the circadian system and environmental schedules is a common condition that is associated with numerous negative health consequences. Chronic frequent exposure to rapid transmeridian travel has been associated with cognitive deficits (Cho et al, 2000) and mood disturbance (Ballard et al, 2006), as well as with reduced longevity in animal models (Davidson et al, 2006). Likewise, ‘social jet lag’, associated with relatively delayed sleep timing on non-work days, has been linked to obesity (Roenneberg et al, 2012) and cardiometabolic risk (Wong et al, 2015). Accumulating evidence points to associations of circadian disruption with mood disorders (Lyall et al, 2018)

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