title: Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep.
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.
authors.affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK.
authors.forename: Gareth
authors.initials: G
authors.lastname: Banks
authors.affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK.
authors.forename: Ines
authors.initials: I
authors.lastname: Heise
authors.affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK.
authors.forename: Becky
authors.initials: B
authors.lastname: Starbuck
authors.affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK.
authors.forename: Tamzin
authors.initials: T
authors.lastname: Osborne
authors.affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Wisby
authors.affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Potter
authors.affiliation: MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Jackson
authors.affiliation: Nuffield Laboratory of Ophthalmology (Nuffield Department of Clinical Neurosciences), University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Russell G
authors.initials: RG
authors.lastname: Foster
authors.affiliation: Nuffield Laboratory of Ophthalmology (Nuffield Department of Clinical Neurosciences), University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Stuart N
authors.initials: SN
authors.lastname: Peirson
authors.affiliation: MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire, UK. Electronic address: p.nolan@har.mrc.ac.uk.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Nolan
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology*; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D012890:Sleep / Q000235:genetics* / Q000502:physiology*; D014792:Visual Acuity / Q000235:genetics* / Q000502:physiology*
keywords: Aging; Circadian; Light input; Mouse strain; Sleep