ナカムラ　タカヒロ   NAKAMURA Takahiro   中村　孝博    所属   明治大学  農学部    職種   専任教授
言語種別	英語
発行・発表の年月	2015/09
形態種別	学術雑誌
査読	査読あり
標題	Age-Related Changes in the Circadian System Unmasked by Constant Conditions
執筆形態	共著(筆頭者)
掲載誌名	eNeuro
出版社・発行元	Society for Neuroscience
巻・号・頁	2(4)
著者・共著者	Nakamura TJ, Nakamura W, Tokuda IT, Ishikawa T, Kudo T, Colwell CS, Block GD
概要	Circadian timing systems, like most physiological processes, cannot escape the effects of aging. With age, humans experience decreased duration and quality of sleep. Aged mice exhibit decreased amplitude and increased fragmentation of the activity rhythm, and lengthened circadian free-running period in both light-dark (LD) and constant dark (DD) conditions. Several studies have shown that aging impacts neural activity rhythms in the central circadian clock in the suprachiasmatic nucleus (SCN). However, evidence for age-related disruption of circadian oscillations of clock genes in the SCN has been equivocal. We hypothesized that daily exposure to LD cycles masks the full impact of aging on molecular rhythms in the SCN. We performed ex vivo bioluminescent imaging of cultured SCN slices of young and aged PER2::luciferase knock-in (PER2::LUC) mice housed under LD or prolonged DD conditions. Under LD conditions, the amplitude of PER2::LUC rhythms differed only slightly between SCN explants from young and aged animals; under DD conditions, the PER2::LUC rhythms of aged animals showed markedly lower amplitudes and longer circadian periods than those of young animals. Recordings of PER2::LUC rhythms in individual SCN cells using an electron multiplying charge-coupled device camera revealed that aged SCN cells showed longer circadian periods and that the rhythms of individual cells rapidly became desynchronized. These data suggest that aging degrades the SCN circadian ensemble, but that recurrent LD cycles mask these effects. We propose that these changes reflect a decline in pacemaker robustness that could increase vulnerability to environmental challenges, and partly explain age-related sleep and circadian disturbances.
DOI	10.1523/ENEURO.0064-15.2015.