Ageing and the circadian and homeostatic regulation of human sleep during forced desynchrony of rest, melatonin and temperature rhythms

Abstract

1. The circadian timing system has been implicated in age-related changes in sleep structure, timing and consolidation in humans. 2. We investigated the circadian regulation of sleep in 13 older men and women and 11 young men by forced desynchrony of polysomnographically recorded sleep episodes (total, 482; 9 h 20 min each) and the circadian rhythms of plasma melatonin and core body temperature. 3. Stage 4 sleep was reduced in older people. Overall levels of rapid eye movement (REM) sleep were not significantly affected by age. The latencies to REM sleep were shorter in older people when sleep coincided with the melatonin rhythm. REM sleep was increased in the first quarter of the sleep episode and the increase of REM sleep in the course of sleep was diminished in older people. 4. Sleep propensity co-varied with the circadian rhythms of body temperature and plasma melatonin in both age groups. Sleep latencies were longest just before the onset of melatonin secretion and short sleep latencies were observed close to the temperature nadir. In older people sleep latencies were longer close to the crest of the melatonin rhythm. 5. In older people sleep duration was reduced at all circadian phases and sleep consolidation deteriorated more rapidly during the course of sleep, especially when the second half of the sleep episode occurred after the crest of the melatonin rhythm. 6. The data demonstrate age-related decrements in sleep consolidation and increased susceptibility to circadian phase misalignment in older people. These changes, and the associated internal phase advance of the propensity to awaken from sleep, appear to be related to the interaction between a reduction in the homeostatic drive for sleep and a reduced strength of the circadian signal promoting sleep in the early morning.

Figures

Figure 1. Sleep structure in older (•) and young (^) subjects while sleeping at their habitual bedtimes

Data are plotted per third of the sleep episode. REM sleep (A) and SWS (B) are expressed as percentage of total sleep time (TST) per third of the sleep episode. Wakefulness (C) is expressed as percentage of recording time (RT) per third of the sleep episode. Vertical bars indicate s.e.m.

Figure 2. Double raster plot of the protocol in a young (1122, age 23 years) and an older subject (1215, age 64 years)

Successive days are plotted next to and beneath each other. Open bars indicate the timing of the scheduled sleep episodes. Filled bars within these open bars indicate wakefulness. The estimated progression of the temperature nadir and the melatonin crest are indicated by the solid and dashed line, respectively. Stippled areas indicate constant routines.

Figure 3. Circadian variation of core body temperature (A), plasma melatonin (B), sleep efficiency (C), latency to sleep onset (D) and latency to REM sleep (E and F) in older (•) and young (^) subjects

All data are plotted relative to the circadian phase of the core body temperature rhythm and are double plotted. Sleep latency, REM latency and sleep efficiency data are plotted with a 60 deg resolution at the mid-point of each bin. Mean REM latencies represent means of the median values in each subject (E). Individual REM sleep latencies are also represented (F) and the data from the older subjects are plotted to the left of the data from the young subjects in this panel. Plasma melatonin and core body temperature data are plotted with a 15 deg resolution at the mid-point of each bin. The waveform of plasma melatonin was derived by folding the data at the period of the core body temperature rhythm. Variation of plasma melatonin data was expressed as z-scores within each subject and then averaged across subjects. Circadian variation of core body temperature data was computed from the circadian waveform that was fitted to the raw temperature data, and expressed as deviation from the mean. All subjects contributed to every plotted data point for the temperature and sleep parameters, whereas 10 older and 11 young subjects contributed to the plasma melatonin data. Vertical bars indicate one s.e.m.

Figure 4. Main effects of circadian phase of the core body temperature cycle (left-hand panels) and time elapsed since the start of the sleep episode (right-hand panels) in older (•) and young (^) subjects

Results are presented for body temperature (A), plasma melatonin (B), wakefulness within scheduled sleep episodes (C), stage 1 sleep (D), stage 2 sleep (E), stage 3 sleep (F), stage 4 sleep (G) and REM sleep (H). Circadian waveforms are all double plotted with a resolution of 45 deg, except core body temperature and plasma melatonin waveforms, which are plotted with a resolution of 15 deg. Sleep-dependent main effects are plotted at quarters of the sleep episode (i.e. a resolution of 140 min). Sleep-dependent main effects of temperature and plasma melatonin are plotted with a resolution of 70 min. All parameters are plotted at the centre of the bins. Body temperature data (deviation from mean, °C) represent the fitted circadian component (left-hand panels) and the fitted sleep-dependent component (right-hand panels) as assessed by non-orthogonal spectral analysis. Plasma melatonin data are expressed as z-scores. Note that the first data point for the sleep-dependent modulation of body temperature and plasma melatonin represents the mean of these values during the first 35 min before lights out and the first 35 min thereafter. The s.e.m. is represented by the vertical bars and represents the between-subject standard error of the mean in each age group. Vigilance state parameters are expressed as percentage of total recording time (TRT) (wakefulness) or percentage of sleep time (stage 1, 2, 3, 4, REM).

Figure 5. Quasi-3-D representation of wakefulness in scheduled sleep episodes as a function of circadian phase of the core body temperature cycle and time in sleep episode in older and young subjects

Data are plotted per 30 circadian deg and per fifth of the sleep episode (112 min). All data are plotted at the mid-point of the bins. The mean approximate corresponding times during entrainment in young and older people (according to Duffy et al. 1998) are also indicated.

Figure 6. Effect of interaction between circadian phase of the start of the sleep episode and time since the start of the sleep episode on wakefulness within quarters of the scheduled sleep episodes in older (•) and young (^) subjects

Sleep episodes were sorted according to the circadian phase of the core body temperature rhythm at lights out (resolution, 60 deg). A, sleep episodes starting at 180 deg (range, 150-210 deg); B, 240 deg (range, 210-270 deg); C, 300 deg (range, 270-330 deg); D, 360 deg (range, 270-390 (i.e. 30) deg; E, 60 deg (range, 30-90 deg) F, 120 deg (range, 90-150 deg). Wakefulness is expressed as percentage of recording time. Insets reflect the circadian component of the body temperature rhythm in young and older subjects and boxes indicate (approximately) the part of the circadian cycle traversed from start of sleep to end of sleep.

Figure 7. Variation of wakefulness within quarters of sleep episodes (I-IV) as a function of the circadian phase of the plasma melatonin rhythm in older (•) and young (^) subjects

The fitted maximum of the melatonin rhythm is represented by 0 deg. Wakefulness is expressed as percentage of recording time obtained in each bin. Bin width is 30 deg for wakefulness and data are plotted at the mid-points of each bin. Melatonin data are expressed as z-scores and plotted with a resolution of 15 deg. Vertical dotted lines are plotted at the onset of melatonin secretion (-90 deg) and at the end of that part of the circadian cycle during which melatonin was elevated in plasma (90 deg). Vertical bars represent the between-subject s.e.m. within each age group (•: older people, n= 10; ^: young people, n= 11). Data are double plotted.