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Age-Related Changes in the Circadian System Unmasked by Constant Conditions(1,2,3).

Nakamura TJ, Nakamura W, Tokuda IT, Ishikawa T, Kudo T, Colwell CS, Block GD - eNeuro (2015)

Bottom Line: Circadian timing systems, like most physiological processes, cannot escape the effects of aging.With age, humans experience decreased duration and quality of sleep.These data suggest that aging degrades the SCN circadian ensemble, but that recurrent LD cycles mask these effects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Life Sciences, School of Agriculture, Meiji University , Kanagawa, Kawasaki 214-8571, Japan ; Faculty of Pharmaceutical Sciences, Teikyo Heisei University , Tokyo 164-8530, Japan ; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles , Los Angeles, California 90024-1759.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Effects of aging on PER2::LUC rhythms in SCN explants from mice maintained in DD. A, Representative images of PER2::LUC in SCN explants collected from young and aged mice maintained in DD for 10 d, recorded by an EM-CCD camera at 30, 42, 108, and 120 h after the start of recording. B, Representative graphical (top) and raster (below) plots of PER2::LUC rhythms of individual cells in SCN explants of young and aged SCNs. C, D, Phase spreads (C) and normalized amplitudes (D) of PER2::LUC rhythms averaged over young (red) and aged (green) SCNs are shown over five cycles. E, Ratios of free-running circadian period change from the first to the fifth cycle of PER2::LUC rhythms in 50 individual SCN cells are shown. Data are shown as the mean ± SD. n = 6 per group. *p < 0.05 (t test). Scale bar, 100 μm.
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Figure 3: Effects of aging on PER2::LUC rhythms in SCN explants from mice maintained in DD. A, Representative images of PER2::LUC in SCN explants collected from young and aged mice maintained in DD for 10 d, recorded by an EM-CCD camera at 30, 42, 108, and 120 h after the start of recording. B, Representative graphical (top) and raster (below) plots of PER2::LUC rhythms of individual cells in SCN explants of young and aged SCNs. C, D, Phase spreads (C) and normalized amplitudes (D) of PER2::LUC rhythms averaged over young (red) and aged (green) SCNs are shown over five cycles. E, Ratios of free-running circadian period change from the first to the fifth cycle of PER2::LUC rhythms in 50 individual SCN cells are shown. Data are shown as the mean ± SD. n = 6 per group. *p < 0.05 (t test). Scale bar, 100 μm.

Mentions: Statistical table: results of two-way repeated-measures ANOVA for datasets of phase and amplitude in PMT recordings (Figs. 1C,D, 2C,D), and datasets of phase spread and amplitude in EM-CCD camera recordings (Fig. 3C,D)


Age-Related Changes in the Circadian System Unmasked by Constant Conditions(1,2,3).

Nakamura TJ, Nakamura W, Tokuda IT, Ishikawa T, Kudo T, Colwell CS, Block GD - eNeuro (2015)

Effects of aging on PER2::LUC rhythms in SCN explants from mice maintained in DD. A, Representative images of PER2::LUC in SCN explants collected from young and aged mice maintained in DD for 10 d, recorded by an EM-CCD camera at 30, 42, 108, and 120 h after the start of recording. B, Representative graphical (top) and raster (below) plots of PER2::LUC rhythms of individual cells in SCN explants of young and aged SCNs. C, D, Phase spreads (C) and normalized amplitudes (D) of PER2::LUC rhythms averaged over young (red) and aged (green) SCNs are shown over five cycles. E, Ratios of free-running circadian period change from the first to the fifth cycle of PER2::LUC rhythms in 50 individual SCN cells are shown. Data are shown as the mean ± SD. n = 6 per group. *p < 0.05 (t test). Scale bar, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596014&req=5

Figure 3: Effects of aging on PER2::LUC rhythms in SCN explants from mice maintained in DD. A, Representative images of PER2::LUC in SCN explants collected from young and aged mice maintained in DD for 10 d, recorded by an EM-CCD camera at 30, 42, 108, and 120 h after the start of recording. B, Representative graphical (top) and raster (below) plots of PER2::LUC rhythms of individual cells in SCN explants of young and aged SCNs. C, D, Phase spreads (C) and normalized amplitudes (D) of PER2::LUC rhythms averaged over young (red) and aged (green) SCNs are shown over five cycles. E, Ratios of free-running circadian period change from the first to the fifth cycle of PER2::LUC rhythms in 50 individual SCN cells are shown. Data are shown as the mean ± SD. n = 6 per group. *p < 0.05 (t test). Scale bar, 100 μm.
Mentions: Statistical table: results of two-way repeated-measures ANOVA for datasets of phase and amplitude in PMT recordings (Figs. 1C,D, 2C,D), and datasets of phase spread and amplitude in EM-CCD camera recordings (Fig. 3C,D)

Bottom Line: Circadian timing systems, like most physiological processes, cannot escape the effects of aging.With age, humans experience decreased duration and quality of sleep.These data suggest that aging degrades the SCN circadian ensemble, but that recurrent LD cycles mask these effects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Life Sciences, School of Agriculture, Meiji University , Kanagawa, Kawasaki 214-8571, Japan ; Faculty of Pharmaceutical Sciences, Teikyo Heisei University , Tokyo 164-8530, Japan ; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles , Los Angeles, California 90024-1759.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus