Decreased sensitivity to phase-delaying effects of moderate intensity light in older subjects

Abstract

Aging is associated with a change in the relationship between the timing of sleep and circadian rhythms, such that the rhythms occur later with respect to sleep than in younger adults. To investigate whether a difference in the phase-delaying response to evening light contributes to this, we conducted a 9-day inpatient study in 10 healthy older (≥65 y.o.) subjects. We assessed circadian phase in a constant routine, exposed each subject to a 6.5 h broad-spectrum light stimulus beginning in the early biological night, and reassessed circadian phase. The stimuli spanned a range from very dim (∼2 lx) to very bright (∼8000 lx) indoor light. We found a significant dose–response relationship between illuminance and the phase shift of the melatonin rhythm, with evidence that sensitivity, but not the maximal response to light, differed from that of younger adults. These findings suggest an age-related reduction in the phase-delaying response to moderate light levels. However, our findings alone do not explain the altered phase relationship between sleep and circadian rhythms associated with aging.

Introduction

Healthy aging is associated with changes in sleep quality, duration, and timing. These changes include less of the deeper sleep stages (stages 3 and 4, slow wave sleep), an increase in the number of awakenings during the night, and earlier sleep–wake times. These age-related changes in sleep occur even in the absence of clinically-significant sleep disorders such as sleep disordered breathing or periodic limb movement disorder.

The circadian timing system is one of the two major regulatory processes influencing sleep [20], [22], [67], the other being the homeostatic pressure for sleep. It is a major determinant of sleep timing, allows for consolidation of sleep towards the end of the sleep episode, and influences the distribution of sleep stages within a sleep episode. Because of these influences on sleep, age-related changes in the circadian timing system have been hypothesized to contribute to the observed age-related changes in sleep.

The circadian system in humans has an average period (cycle length) that is longer than 24 h [15], [18], [34], [61], and is entrained (synchronized) to the 24 h day by regular exposure to light and darkness [60]. Light has a phase-dependent effect on the circadian system [21], with light exposure during the late subjective day/early subjective night causing phase delay shifts (to a later hour), light during the late subjective night/early subjective day causing phase advance shifts (to an earlier hour), and light exposure during the subjective daytime causing very small phase shifts [35], [39], [47]. The effects of light on the circadian system are determined not only by the timing of light exposure, but by other factors including the intensity [64], wavelength [7], [45], [56], duration [49], [50] and prior light exposure history [19], [32], [54]. We and others have reported previously that the relative timing between the phase of circadian rhythms and the timing of the nocturnal sleep episode is significantly different between healthy older and young adults [26], [27], [44], and we have found that this change in phase relationship does not appear to be related to an age-related difference in the length or lability of the endogenous circadian period [18]. As light exposure is required to maintain entrainment of the non-24 h circadian clock to the 24 h day, and the relative phase alignment of the internal clock to the external day is directly dependent upon the qualities of the light, age-related changes in light sensitivity could contribute to the observed age-related differences in the phase relationship between sleep and the circadian timing system.

There is evidence from animal studies that there is a reduction in light sensitivity of the circadian system with advancing age, including smaller phase shifts in response to light [4], [66] (see [59] for review), a smaller range of entrainment [48], greater light levels necessary for stable entrainment [43], and changes in the rate of re-entrainment [11], [62]. These reductions at the whole animal level may be due to observed age-related changes in the response to light at the cellular level in the suprachiasmatic nucleus (SCN, the locus of the central circadian pacemaker in mammals), including a higher threshold for cellular responses [66] and/or decreased response to light [4], [42], [55]. There is also evidence that age-related structural changes in the circadian and/or visual systems may contribute to a reduction in light sensitivity, including reduced light transmission through the eye [16], [65] (especially of shorter wavelengths [8]), and a reduction in the number of circadian photoreceptors [52].

A change in the photic sensitivity of the human circadian timing system might manifest as a change in sleep patterns. Some reports suggest that older individuals living in their home environments receive lower levels of light exposure and fewer minutes of bright light exposure per day than do young adults [14], [28], [51], although not all studies agree on this [37]. Institutionalized elderly have been reported to receive even less bright light than healthy elders [53], and there is also an association between daytime light exposure and nighttime sleep quality and consolidation in both institutionalized and healthy older people [36], [53], [57] with exposure to greater amounts of daytime light associated with better nighttime sleep quality. A recent study comparing light exposure between young and middle-aged subjects found that while the daily exposure to different levels of light did not differ with age, the pattern of light exposure across the day was different [38]. Timed artificial light exposure has been shown to improve sleep maintenance insomnia in community-dwelling older people [13], and increasing the duration and strength of daytime lighting has been reported to be associated with greater nighttime sleep consolidation and improved sleep efficiency in institutionalized elders [2], [29], [58].

Together, these reports suggest that reduced light exposure levels and/or a decreased sensitivity to light with aging might contribute to age-related increases in sleep disruption and the age-related alteration in the phase relationship between sleep timing and the timing of the biological clock that have been reported previously. The current study was designed to determine whether the sensitivity or capacity of the human circadian system to respond to a single, phase-delaying, broad-spectrum white light pulse was reduced with age.