Responsiveness of the aging circadian clock to light

Abstract

The present study assessed whether advances in sleep times and circadian phase in older adults might be due to decreased responsiveness of the aging circadian clock to light. Sixteen young (29.3+/-5.6 years) and 14 older adults (67.1+/-7.4 years) were exposed to 4h of control dim (10lux) or bright light (3500lux) during the night. Phase shifts of the melatonin rhythm were assessed from the nights before and after the light exposure. Bright light delayed the melatonin midpoint in both young and older adults (p<0.001). Phase delays for the older subjects were not significantly different from those of the young subjects for either the bright or dim light conditions. The magnitude of phase delays was correlated with both sleep offset and phase angle in the older, but not the younger subjects. The present results indicate that at light intensities commonly used in research as well as clinical practice older adults are able to phase delay to the same extent as younger subjects.

Figure 1

Schematic of the experimental protocol. Subjects were admitted for 4 nights and 3 days under constant conditions during daytime hours with 8 hours sleep in dark at their habitual time (dark bars). Half of the subjects also participated in a 4 night/3 day dim control condition (see methods). Blood samples were taken throughout the baseline and post-treatment nights to assess light-induced changes in the circadian melatonin rhythm. On the third night, subjects were exposed to 4 hours of dim control or bright light (3,500 lux for 3 h, plus 1 hour of intermediate illumination), beginning 5 hours before the temperature minimum.

Figure 2

Average sleep times and circadian phase markers for the young and older subjects. The interval between sleep onset and sleep offset, measured by actigraphy on the week prior to admission, is depicted by the gray bar. The timing of Tmin (▼) and melatonin midpoint on the baseline night (■) and on the night following the light exposure (□) are indicated. The global timing of sleep (onset and offset) and circadian phase markers (DLMO 50%, melatonin midpoint, DLMOff 50%, Tmin) at baseline was earlier in the older adults (p = 0.052). The phase angles between the circadian phase markers and the timing of sleep were not different for the two groups.

Figure 3

Treatment-induced changes of the nocturnal melatonin rhythm in young (A, B) and older (C, D) adults. Subjects were exposed to 4 hours of dim control (A, C) or bright (B, D) light on the treatment night. Melatonin levels, measured throughout the night prior to (dashed) and following (solid line) the treatment night, are plotted as a percent of maximum.

Figure 4

Treatment-induced phase delays of the melatonin midpoint. 4 hours exposure to bright light (open bars) delayed the melatonin rhythm in both the young (p < 0.001, n = 16) and older (p < 0.001, n = 14) groups. The melatonin midpoint did not significantly change after awakening for 4 hours under dim light (n = 7 - 8). Phase delays following bright light exposure were significantly greater than following the dim control condition (p < 0.001). The magnitude of phase delays were not significantly different between the young and older adults.

Figure 5

Correlation between habitual sleep offset and the magnitude of light-induced phase delays. A) There was no association between sleep offset and phase delays in the younger subjects. B) In the older subjects, the magnitude of phase delays was significantly correlated with habitual time of awakening (r = 0.70, p = 0.008), with earlier wake time associated with smaller phase delays.

Figure 5

Correlation between habitual sleep offset and the magnitude of light-induced phase delays. A) There was no association between sleep offset and phase delays in the younger subjects. B) In the older subjects, the magnitude of phase delays was significantly correlated with habitual time of awakening (r = 0.70, p = 0.008), with earlier wake time associated with smaller phase delays.

Figure 6

Correlation between phase angle and the magnitude of light-induced phase delays. Phase angle was calculated as the interval between melatonin midpoint and habitual sleep offset. A) There was no association between phase angle and phase delays in the younger subjects. B) In the older group of subjects, the magnitude of phase delays was significantly correlated with phase angle r = 0.68, p = 0.010). A shorter interval between melatonin midpoint and sleep offset was associated with smaller phase delays.

Figure 6

Correlation between phase angle and the magnitude of light-induced phase delays. Phase angle was calculated as the interval between melatonin midpoint and habitual sleep offset. A) There was no association between phase angle and phase delays in the younger subjects. B) In the older group of subjects, the magnitude of phase delays was significantly correlated with phase angle r = 0.68, p = 0.010). A shorter interval between melatonin midpoint and sleep offset was associated with smaller phase delays.

Figure 7

Illustration of the association between phase delays of the melatonin midpoint and sleep parameters in individual older subjects. Habitual sleep onset and sleep offset is depicted by the beginning and end of the gray bar. Phase delays are the difference between baseline (■) and post-treatment (□) melatonin midpoints. Both early wake times and/or a smaller interval between sleep offset and baseline circadian phase (e.g. melatonin midpoint) were associated with smaller phase shifts.