Abstract
The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep.
Highlights
In healthy individuals, a rhythmic sleep/wake cycle is maintained through the interaction of homeostatic and circadian mechanisms, as well as being modulated by external cues
The homeostatic process refers to an increase of sleep pressure that accumulates during wakefulness and is relieved by sleep (Borbely, 1982)
The interactions between retinal light input pathways, the circadian clock, and the sleep homeostat are well maintained in healthy individuals, aging is known to have a negative impact on all these processes, leading to disrupted circadian rhythms and sleep/wake cycles in older individuals
Summary
A rhythmic sleep/wake cycle is maintained through the interaction of homeostatic and circadian mechanisms, as well as being modulated by external cues. The timing of the sleep/wake cycle is regulated by the internal circadian clock, which provides an innate biological rhythm exerting control over a wide range of physiological and behavioral processes. The most influential external cue for both sleep and circadian rhythms is light. The interactions between retinal light input pathways, the circadian clock, and the sleep homeostat are well maintained in healthy individuals, aging is known to have a negative impact on all these processes, leading to disrupted circadian rhythms and sleep/wake cycles in older individuals. The reported effects of aging include an increased occurrence of cataracts (Klein and Klein, 2013), loss of retinal photoreceptors (Gao and Hollyfield, 1992), reduced circadian regulation of melatonin and temperature (Pandi-Perumal et al, 2005; Weinert, 2010), a reduction in sleep duration and
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