Plasma melatonin rhythms in young and older humans during sleep, sleep deprivation, and wake

Abstract

Study objectives: To determine the effects of sleep and sleep deprivation on plasma melatonin concentrations in humans and whether these effects are age-dependent.

Design: At least 2 weeks of regular at-home, sleep/wake schedule followed by 3 baseline days in the laboratory and at least one constant routine (sleep deprivation).

Setting: General Clinical Research Center (GCRC), Brigham and Women's Hospital, Boston, MA.

Participants: In Study 1, one group (<10 lux when awake) of 19 young men (18-30 y) plus a second group (<2 lux when awake) of 15 young men (20-28 y) and 10 young women (19-27 y); in Study 2, 90 young men (18-30 y), 18 older women (65-81 y), and 11 older men (64-75 y). All participants were in good health, as determined by medical and psychological screening.

Interventions: One to three constant routines with interspersed inversion of the sleep/wake cycle in those with multiple constant routines.

Measurements and results: Examination of plasma melatonin concentrations and core body temperature. Study 1. There was a small, but significant effect of sleep deprivation of up to 50 hours on melatonin concentrations (increase of 9.81 +/- 3.73%, P <0.05, compared to normally timed melatonin). There was also an effect of circadian phase angle with the prior sleep episode, such that if melatonin onset occurred <8 hours after wake time, the amplitude was significantly lower (22.4% +/- 4.79%, P <0.001). Study 2. In comparing melatonin concentrations during sleep to the same hours during constant wakefulness, in young men, melatonin amplitude was 6.7% +/- 2.1% higher(P <0.001) during the sleep episode. In older men, melatonin amplitude was 37.0% +/- 12.5% lower (P <0.05) during the sleep episode and in older women, melatonin amplitude was non-significantly 10.9% +/- 8.38% lower (P = 0.13) during the sleep episode.

Conclusions: Both sleep and sleep deprivation likely influence melatonin amplitude, and the effect of sleep on melatonin appears to be age dependent.

Figure 1

Increase in normalized plasma melatonin amplitude with time awake. A fitted linear regression (dashed line) is shown. The dashed box indicates the normal phase position of melatonin onset in entrained, young adults (12.5-17.1 h after wake onset). Note, 14 h of melatonin data (CR) are normalized to 8 h of melatonin data (sleep episode) for the purposes of this analysis; thus, an amplitude of 1.0 does not mean that melatonin during the constant routine was equal to melatonin during the sleep episode. Normalization is necessary given the large interindividual variation of plasma melatonin peaks.

Figure 2

Average (±SEM) plasma melatonin during a single episode of extended (50 h) wakefulness (n=25, young men and women, Group 2 in Study 1). Data were averaged per hour within and then between subjects. The first melatonin cycle is replotted as a dashed line in the time frame of the second cycle for comparison.

Figure 3

Average (±SEM) plasma melatonin in young (top, n=90) and older (bottom, n=29) subjects during a normally phased sleep episode (closed boxes) and a constant routine where they remained awake at the same clock hours (open circles). Data were aligned such that each subject's wake time was graphically adjusted to 08:00 and the data from the baseline day and night and from the CR expressed relative to wake time; sleep time is from 24:00 to 08:00. Melatonin data were averaged hourly within and then across subjects.