title: Aging differentially affects the re-entrainment response of central and peripheral circadian oscillators.
abstract: Aging produces a decline in the amplitude and precision of 24 h behavioral, endocrine, and metabolic rhythms, which are regulated in mammals by a central circadian pacemaker within the suprachiasmatic nucleus (SCN) and local oscillators in peripheral tissues. Disruption of the circadian system, as experienced during transmeridian travel, can lead to adverse health consequences, particularly in the elderly. To test the hypothesis that age-related changes in the response to simulated jet lag will reflect altered circadian function, we examined re-entrainment of central and peripheral oscillators from young and old PER2::luciferase mice. As in previous studies, locomotor activity rhythms in older mice required more days to re-entrain following a shift than younger mice. At the tissue level, effects of age on baseline entrainment were evident, with older mice displaying earlier phases for the majority of peripheral oscillators studied and later phases for cells within most SCN subregions. Following a 6 h advance of the light:dark cycle, old mice displayed slower rates of re-entrainment for peripheral tissues but a larger, more rapid SCN response compared to younger mice. Thus, aging alters the circadian timing system in a manner that differentially affects the re-entrainment responses of central and peripheral circadian clocks. This pattern of results suggests that a major consequence of aging is a decrease in pacemaker amplitude, which would slow re-entrainment of peripheral oscillators and reduce SCN resistance to external perturbation.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Sellix
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Evans
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Leise
authors.forename: Oscar
authors.initials: O
authors.lastname: Castanon-Cervantes
authors.forename: DiJon D
authors.initials: DD
authors.lastname: Hill
authors.forename: Patrick
authors.initials: P
authors.lastname: DeLisser
authors.forename: Gene D
authors.initials: GD
authors.lastname: Block
authors.forename: Michael
authors.initials: M
authors.lastname: Menaker
authors.forename: Alec J
authors.initials: AJ
authors.lastname: Davidson
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001683:Biological Clocks / Q000502:physiology; D001921:Brain / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D003627:Data Interpretation, Statistical; D007091:Image Processing, Computer-Assisted; D020179:Jet Lag Syndrome / Q000503:physiopathology; D008156:Luciferases / Q000235:genetics / Q000502:physiology; D049449:Luminescence; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009043:Motor Activity / Q000502:physiology; D056950:Period Circadian Proteins / Q000235:genetics / Q000502:physiology; D017933:Peripheral Nervous System / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D008156:Luciferases