Our current study examined the relationship between light intensity and the circadian phase delay response to a single 6.5-h light stimulus in healthy older people. We found that in healthy older people, the circadian rhythms of both core body temperature and plasma melatonin were shifted in parallel in response to the 6.5-h experimental light stimulus, and that there was a significant relationship between illuminance and the phase-delay shift of both the melatonin and temperature rhythms. The illuminance-response relationship using melatonin data provided a much better model fit (adj. R2
= 0.86) than did the core body temperature data (adj. R2
= 0.27), likely due to the greater confidence in the accuracy of the melatonin phase data [41
We also compared the results of our study in older subjects to a previous study we had conducted in younger adults in order to determine if there was an age-related difference in the response to this phase-delaying light stimulus. We found that some aspects of the circadian response to the light stimulus in older subjects did not differ from responses observed previously in young adults. The maximum phase shift obtainable to a single 6.5-h light stimulus in the older adults in this study (the c
term in the 4-parameter model) was equivalent to that obtained in young adults in similar studies [31
]. The progressive delay drift of phase due to the 24.2 h average intrinsic period and non-photic influences on the circadian timing system was also similar between the healthy older and younger adults, as evidenced by the similar values obtained for the a
term in the 4-paramater models fit to the data, representing the predicted shift in response to a 0 lux stimulus.
We did observe a difference in the sensitivity of the system (the b term in the 4-parameter model, representing the illuminance level at which 50% of the asymptotic maximum response is observed) between the older and young subjects (, compare solid and dashed lines). The greater b term reflects a rightward shift of the model fit to the data from the older subjects, indicating that they are less responsive to low-to-moderate levels of light (~50–1,000 lux). Given that pupil dynamics and lens opacity can change with aging, corneal light exposure may be quite different from retinal light exposure in older subjects, and the change we observed may be due to a change in the effective retinal illumination, rather than representing an age-related reduction in circadian light sensitivity. Future studies focused on this narrow illuminance range, with larger numbers of older and young participants may be able to address this question.
Our current findings are consistent with several previous studies in humans that also did not find significant differences in the magnitude of phase delay shifts elicited by late evening/early night light exposure when those light levels were very high or very low. In a previous study we conducted in which subjects were exposed to three consecutive nights of exposure to 5 h bright indoor light, we did not find significant differences between young and older subjects in the size of the phase delay shifts [40
]. The intensity of light used in that study, however, was so large (9,500 lux) as to saturate the circadian timing system’s ability to respond to light. It would therefore only have been able to detect a change in the maximum response to light, as opposed to any change in sensitivity. A recent study of the melatonin-suppressing effects of monochromatic evening light in young and older females found no change in response to long wavelength (548 nm) visible light [33
]. Another recent study that compared circadian phase-shifting responses to dim (10 lux) and bright (3,500 lux) light in young and older adults found no differences between the two age groups [3
], consistent with our finding of no difference in the response to very dim light or to very bright light.
Our study also found a difference in the degree of melatonin suppression between the older and young subjects’ responses to light. The greatest amount of melatonin suppression that was observed in this study was 78.6%. In response to the same experimental light exposure procedures, all young subjects in our previous study who were exposed to at least 350 lux of light showed at least 92% melatonin suppression [64
]. Those young subjects also displayed a strong dose-response relationship between illuminance and melatonin suppression, with robust melatonin suppression occurring at illuminances at least as bright as room light (>100 lux) and little suppression occurring at illuminances less than room light [64
]. Our current cohort of healthy older individuals, in addition to having a lower capacity to suppress melatonin at any intensity of light, did not show a dose response relationship between melatonin suppression and illuminance. As there was a normal responsiveness of the circadian timing system to the phase delaying effects of light, the melatonin suppression data suggest that there may be an age-related change in the light transmission system between the SCN and the source of plasma melatonin (pineal gland). Alternatively, there may be a pathway from the retina to the SCN or other hypothalamic target that is involved in the acute cessation of melatonin production, but not in entrainment, and this pathway may be selectively affected by aging. In fact, sympathetic innervation of the eye, which is also responsible for sympathetic innervation of the pineal gland [63
], may have diminished capacity with aging [6
] and could account for the variability in melatonin suppression we observed in our subjects.
A recent study by Herljevic et al. reported that melatonin suppression in older women was reduced compared with younger women in response to short wavelength (456 nm) visible light, but they found no age-related change in melatonin suppression in response to longer wavelength (548 nm) light [33
]. That finding is of interest due to the fact that the circadian system of humans and other mammals is most sensitive to shorter wavelengths of visible light [7
], and the specialized retinal ganglion cells that serve as the primary circadian photoreceptors [5
] have a peak sensitivity in that same range. While our broad-spectrum white light stimulus was quite different than the stimulus used by Herljevic et al., it is also the case that both our older and young study populations were predominantly male (80% and 82% respectively), which may explain why we observed age-related differences in melatonin suppression and they did not.
It is important to note that in our study, subjects were extremely healthy, had no sleep complaints, and were screened for major visual deficits and age-related changes in lens pigmentation. Despite this, they had the common features of an aging circadian system, including early habitual wake times (before 07:00), melatonin and core body temperature phases occurring in the latter half of their habitual sleep time, and baseline night sleep efficiencies below 80% [23
]. While we found no significant differences in the response to dim or very bright light in our very healthy older subjects when compared with young adults, we did find differences in the response to moderate levels of light. It should be noted that results from the older subjects in the current study were compared with results from a group of young subjects whose study was completed before the current study began. However, the lighting conditions in both studies were highly controlled, and the protocol and lighting conditions in the current study of older subjects was designed to be the same as that in the prior study in young adults in order that such a comparison could be performed.
It is possible that in older individuals with ocular problems (e.g.,
cataracts), light transmission to the circadian pacemaker could be altered, which in turn could further reduce their responsiveness to moderate levels of light, and even reduce their response to bright light. Even with an intact circadian responsiveness to light, older individuals are likely to be less responsive to the use of light as a treatment for transient circadian rhythm sleep disorders such as jet lag and shift work disorder [1
], due to their reduced ability to sleep at adverse circadian phases [24
]. In a study that used a bright light treatment regimen in middle-aged subjects scheduled to a night work schedule, while the subjects were found to phase-shift by >6 hours in response to the bright light treatment, they did not fully adapt to the 9h shift in sleep timing and therefore had high rates of sleep disruption [12
Our current finding that older subjects show a reduced circadian phase shifting response to moderate levels of nighttime light exposure cannot itself explain the difference in entrained circadian phase we and others have observed in older people [26
]. We have also reported that a change in circadian period does not occur with healthy aging [18
]. Together, these findings suggest that the observed age-related difference in the phase relationship between the timing of sleep and the timing of circadian rhythmicity, and the increased variability in this relationship, are more likely due to differences in the phase-advancing response to morning light and/or differences in light exposure patterns across the waking day between young and older adults. Further investigations focused on the response to morning light and to light exposure patterns across the 24-h day should provide a better understanding of these observations.