Evidence for Neuronal Desynchrony in the Aged Suprachiasmatic Nucleus Clock
Open accessAbstract
Aging is associated with a deterioration of daily (circadian) rhythms in physiology and behavior. Deficits in the function of the central circadian pacemaker in the suprachiasmatic nucleus (SCN) have been implicated, but the responsible mechanisms have not been clearly delineated. In this report, we characterize the progression of rhythm deterioration in mice to 900 d of age. Longitudinal behavioral and sleep–wake recordings in up to 30-month-old mice showed strong fragmentation of rhythms, starting at the age of 700 d. Patch-clamp recordings in this age group revealed deficits in membrane properties and GABAergic postsynaptic current amplitude. A selective loss of circadian modulation of fast delayed-rectifier and A-type K+currents was observed. At the tissue level, phase synchrony of SCN neurons was grossly disturbed, with some subpopulations peaking in anti-phase and a reduction in amplitude of the overall multiunit activity rhythm. We propose that aberrant SCN rhythmicity in old animals—with electrophysiological arrhythmia at the single-cell level and phase desynchronization at the network level—can account for defective circadian function with aging.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
These SCN network changes result in desynchronization and a reduction in the amplitude of neuronal activity rhythms and, ultimately, physiological and behavioural rhythms.
“These SCN network changes result in desynchronization and a reduction in the amplitude of neuronal activity rhythms248,249 and, ultimately, physiological and behavioural rhythms241.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [248]
Some SCN cells become silent in older animals, and SCN neurons lose phase coherence with age.
“some SCN cells become silent in older animals (as measured in vitro), and SCN neurons lose phase coherence with age247,248”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [248]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Welsh, D. K., Logothetis, D., Meister, M., & Reppert, S. (1995) · Neuron · doi:10.1016/0896-6273(95)90214-7 · Cited by 1,535 · see citing works
Eilers, P. H. C. (2003) · Analytical Chemistry · doi:10.1021/ac034173t · Cited by 1,347 · see citing works
Suprachiasmatic Nucleus: Cell Autonomy and Network Properties
Welsh, D. K., Takahashi, J. S., & Kay, S. A. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135919 · Cited by 1,216 · see citing works
Aton, S. J., Colwell, C. S., Harmar, A. J., Waschek, J. A., & Herzog, E. D. (2005) · Nature Neuroscience · doi:10.1038/nn1419 · Cited by 764 · see citing works
Alterations in the circadian rest-activity rhythm in aging and Alzheimer's disease
Witting, W., Kwa, I. H., Eikelenboom, P., Mirmiran, M., & Swaab, D. F. (1990) · Biological Psychiatry · doi:10.1016/0006-3223(90)90523-5 · Cited by 621 · see citing works
Dijk, D., Duffy, J. F., Riel, E., Shanahan, T. L., & Czeisler, C. A. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.0611v.x · Cited by 467 · see citing works
Age-Related Decline in Circadian Output
Nakamura, T. J., Nakamura, W., Yamazaki, S., Kudo, T., Cutler, T., Colwell, C. S., & Block, G. D. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0451-11.2011 · Cited by 386 · see citing works
GABA Synchronizes Clock Cells within the Suprachiasmatic Circadian Clock
Liu, C., & Reppert, S. M. (2000) · Neuron · doi:10.1016/s0896-6273(00)80876-4 · Cited by 340 · see citing works
Living by the clock: The circadian pacemaker in older people
Hofman, M. A., & Swaab, D. F. (2005) · Ageing Research Reviews · doi:10.1016/j.arr.2005.07.001 · Cited by 335 · see citing works
Albus, H., Vansteensel, M. J., Michel, S. H., Block, G. D., & Meijer, J. H. (2005) · Current Biology · doi:10.1016/j.cub.2005.03.051 · Cited by 328 · see citing works
Self-citationThe Significance of Circadian Organization for Longevity in the Golden Hamster
Hurd, M. W., & Ralph, M. R. (1998) · Journal of Biological Rhythms · doi:10.1177/074873098129000255 · Cited by 275 · see citing works
Seasonal Encoding by the Circadian Pacemaker of the SCN
vanderLeest, H. T., Houben, T., Michel, S. H., Deboer, T., Albus, H., Vansteensel, M. J., Block, G. D., & Meijer, J. H. (2007) · Current Biology · doi:10.1016/j.cub.2007.01.048 · Cited by 253 · see citing works
Self-citationDisturbed fluctuations of resting state EEG synchronization in Alzheimer's disease
Stam, C. J., Montez, T., Jones, B. F., Rombouts, S. A. R. B., van der Made, Y., Pijnenburg, Y. A. L., & Scheltens, P. (2005) · Clinical Neurophysiology · doi:10.1016/j.clinph.2004.09.022 · Cited by 242 · see citing works
Molecular aging in human prefrontal cortex is selective and continuous throughout adult life
Erraji-Benchekroun, L., Underwood, M. D., Arango, V., Galfalvy, H., Pavlidis, P., Smyrniotopoulos, P., Mann, J. J., & Sibille, E. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.10.034 · Cited by 236 · see citing works
Schaap, J., Albus, H., vanderLeest, H. T., Eilers, P. H. C., Détári, L., & Meijer, J. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436298100 · Cited by 216 · see citing works
Self-citationEmergence of Noise-Induced Oscillations in the Central Circadian Pacemaker
Ko, C. H., Yamada, Y., Welsh, D. K., Buhr, E. D., Liu, A. C., Zhang, E. E., Ralph, M. R., Kay, S. A., Forger, D. B., & Takahashi, J. S. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000513 · Cited by 212 · see citing works
Wu, Y., Zhou, J., van Heerikhuize, J. J., Jockers, R., & Swaab, D. F. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.06.002 · Cited by 209 · see citing works
Daily Electrical Silencing in the Mammalian Circadian Clock
Belle, M. D. C., Diekman, C. O., Forger, D. B., & Piggins, H. D. (2009) · Science · doi:10.1126/science.1169657 · Cited by 180 · see citing works
Dorsomedial SCN neuronal subpopulations subserve different functions in human dementia
Harper, D. G., Stopa, E. G., Kuo-LeBlanc, V., McKee, A. C., Asayama, K., Volicer, L., Kowall, N. W., & Satlin, A. (2008) · Brain · doi:10.1093/brain/awn049 · Cited by 165 · see citing works
Effects of age on the circadian system
Turek, F. W., Penev, P. D., Zhang, Y., Reeth, O. V., & Zee, P. P. (1995) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(94)00030-5 · Cited by 159 · see citing works
Do the suprachiasmatic nuclei oscillate in old rats as they do in young ones?
Satinoff, E., Li, H., Tcheng, T. K., Liu, C., McArthur, A. J., Medanic, M., & Gillette, M. U. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.265.5.r1216 · Cited by 159 · see citing works
Electrophysiology of the suprachiasmatic circadian clock
Brown, T. M., & Piggins, H. D. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.05.002 · Cited by 152 · see citing works
Fast delayed rectifier potassium current is required for circadian neural activity
Itri, J. N., Michel, S. H., Vansteensel, M. J., Meijer, J. H., & Colwell, C. S. (2005) · Nature Neuroscience · doi:10.1038/nn1448 · Cited by 129 · see citing works
Self-citationSearching for Genes Underlying Behavior: Lessons from Circadian Rhythms
Takahashi, J. S., Shimomura, K., & Kumar, V. (2008) · Science · doi:10.1126/science.1158822 · Cited by 105 · see citing works
Kuhlman, S. J., & McMahon, D. G. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03555.x · Cited by 104 · see citing works
Mahlberg, R., Tilmann, A., Salewski, L., & Kunz, D. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.01.009 · Cited by 102 · see citing works
vanderLeest, H. T., Rohling, J. H. T., Michel, S. H., & Meijer, J. H. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004976 · Cited by 102 · see citing works
Self-citationVasoactive intestinal polypeptide neuron changes in the senile rat suprachiasmatic nucleus
Chee, C. A., Roozendaal, B., Swaab, D. F., Goudsmit, E., & Mirmiran, M. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80070-8 · Cited by 101 · see citing works
Castel, M., & Morris, J. F. (2000) · Journal of Anatomy · doi:10.1046/j.1469-7580.2000.19610001.x · Cited by 100 · see citing works
Effects of normal aging on prefrontal area 46 in the rhesus monkey
Luebke, J. I., Barbas, H., & Peters, A. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2009.12.002 · Cited by 98 · see citing works
Watanabe, A., Shibata, S., & Watanabe, S. (1995) · Brain Research · doi:10.1016/0006-8993(95)00713-z · Cited by 96 · see citing works
Brown, T. M., & Piggins, H. D. (2009) · Journal of Biological Rhythms · doi:10.1177/0748730408327918 · Cited by 92 · see citing works
Endophenotypes in a Dynamically Connected Brain
Smit, D. J. A., Boersma, M., van Beijsterveldt, C. E. M., Posthuma, D., Boomsma, D. I., Stam, C. J., & de Geus, E. J. C. (2010) · Behavior Genetics · doi:10.1007/s10519-009-9330-8 · Cited by 86 · see citing works
Circadian Rhythm in Inhibitory Synaptic Transmission in the Mouse Suprachiasmatic Nucleus
Itri, J. N., Michel, S. H., Waschek, J. A., & Colwell, C. S. (2004) · Journal of Neurophysiology · doi:10.1152/jn.01078.2003 · Cited by 83 · see citing works
Self-citationAge-related changes in electrophysiological properties of the mouse suprachiasmatic nucleus in vitro
Nygård, M., Hill, R. H., Wikström, M. A., & Kristensson, K. (2005) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2004.12.006 · Cited by 82 · see citing works
Palomba, M. L., Nygård, M., Florenzano, F., Bertini, G., Kristensson, K., & Bentivoglio, M. (2008) · Journal of Biological Rhythms · doi:10.1177/0748730408316998 · Cited by 81 · see citing works
Circadian Regulation of A-Type Potassium Currents in the Suprachiasmatic Nucleus
Itri, J. N., Vosko, A. M., Schroeder, A., Dragich, J. M., Michel, S. H., & Colwell, C. S. (2009) · Journal of Neurophysiology · doi:10.1152/jn.00670.2009 · Cited by 79 · see citing works
Self-citationCircadian clock resetting in the mouse changes with age
Biello, S. M. (2009) · AGE · doi:10.1007/s11357-009-9102-7 · Cited by 76 · see citing works
Excitatory Mechanisms in the Suprachiasmatic Nucleus: The Role of AMPA/KA Glutamate Receptors
Michel, S. H., Itri, J. N., & Colwell, C. S. (2002) · Journal of Neurophysiology · doi:10.1152/jn.2002.88.2.817 · Cited by 75 · see citing works
Self-citationRunning Wheel Accessibility Affects the Regional Electroencephalogram during Sleep in Mice
Vyazovskiy, V. V., Ruijgrok, G., Deboer, T., & Tobler, I. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhi110 · Cited by 75 · see citing works
Self-citationOxidation of a potassium channel causes progressive sensory function loss during aging
Cai, S., & Sesti, F. (2009) · Nature Neuroscience · doi:10.1038/nn.2291 · Cited by 72 · see citing works
Duncan, M. J., Herron, J. M., & Hill, S. (2001) · Molecular Brain Research · doi:10.1016/s0169-328x(01)00015-8 · Cited by 67 · see citing works
Tumor Necrosis Factor (TNF) Ligand and TNF Receptor Deficiency Affects Sleep and the Sleep EEG
Deboer, T., Fontana, A., & Tobler, I. (2002) · Journal of Neurophysiology · doi:10.1152/jn.2002.88.2.839 · Cited by 61 · see citing works
Self-citationMorphologic changes in the hypothalamus of the old mouse
Machado-Salas, J. P., Scheibel, M. E., & Scheibel, A. B. (1977) · Experimental Neurology · doi:10.1016/0014-4886(77)90048-6 · Cited by 55 · see citing works
Luebke, J. I., & Chang, Y. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.09.042 · Cited by 47 · see citing works
Short light–dark cycles affect sleep in mice
Deboer, T., Ruijgrok, G., & Meijer, J. H. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05964.x · Cited by 46 · see citing works
Self-citationNygård, M., & Palomba, M. L. (2006) · Chronobiology International · doi:10.1080/07420520500545938 · Cited by 30 · see citing works
Duncan, M. J., Hester, J., Hopper, J. A., & Franklin, K. M. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07186.x · Cited by 27 · see citing works
Registrar's corner acute pancreatitis: updated.
Swaab, D. F., Fliers, E., & Fisser, B. (1985) · PubMed · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sleep and Alzheimer disease pathology--a bidirectional relationship
Ju, Y.-E. S., Lucey, B. P., & Holtzman, D. M. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.269 · Cited by 996 · see citing works
Rhythms of life: circadian disruption and brain disorders across the lifespan
Logan, R. W., & McClung, C. A. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0088-y · Cited by 713 · see citing works
Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration
Musiek, E. S., Lim, M. M., Yang, G., Bauer, A. Q., Qi, L., Lee, Y., Roh, J. H., Ortiz-Gonzalez, X., Dearborn, J. T., Culver, J. P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70317 · Cited by 524 · see citing works
Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease
Musiek, E. S., Xiong, D. D., & Holtzman, D. M. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.121 · Cited by 529 · see citing works
Duffy, J. F., Zitting, K.-M., & Chinoy, E. D. (2015) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2015.08.002 · Cited by 367 · see citing works
Circadian Rhythms, Sleep, and Disorders of Aging
Mattis, J., & Sehgal, A. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.02.003 · Cited by 369 · see citing works
Circadian rhythms, time-restricted feeding, and healthy aging
Manoogian, E. N. C., & Panda, S. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.12.006 · Cited by 330 · see citing works
Skeldon, A. C., Derks, G., & Dijk, D.-J. (2016) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2015.05.011 · Cited by 165 · see citing works
Mammalian circadian systems: Organization and modern life challenges
Finger, A., & Kramer, A. (2021) · Acta Physiologica · doi:10.1111/apha.13548 · Cited by 117 · see citing works
Thyroid Hormone Signaling and Homeostasis During Aging
Bowers, J., Terrien, J., Clerget-Froidevaux, M. S., Gothié, J. D., Rozing, M. P., Westendorp, R. G. J., van Heemst, D., & Demeneix, B. A. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1056 · Cited by 117 · see citing works
Loss of dopamine disrupts circadian rhythms in a mouse model of Parkinson's disease
Fifel, K., & Cooper, H. M. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.08.024 · Cited by 80 · see citing works
Aging, circadian disruption and neurodegeneration: Interesting interplay
Verma, A. K., Singh, S., & Rizvi, S. I. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2022.112076 · Cited by 55 · see citing works
- Authors
- Farajnia, S., Michel, S., Deboer, T., vanderLeest, H. T., Houben, T., Rohling, J. H. T., Ramkisoensing, A., Yasenkov, R., & Meijer, J. H.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Meijer, Johanna H.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-04-25
- Volume
- 32
- Issue
- 17
- Pages
- 5891-5899
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6703600
- OpenAlex
- W1969904423
- Cited by
- 230
- References
- 49
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 10 · 2023: 24 · 2022: 11 · 2021: 18 · 2020: 15 · 2019: 17 · 2018: 13 · 2017: 16 · 2016: 21 · 2015: 21 · 2014: 14 · 2013: 14 · 2012: 3
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (818.02.016)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- suprachiasmatic nucleus, phase synchronization, circadian pacemaker, delayed rectifier potassium current, A-type potassium current, antiphase oscillations
- MeSH terms
- Action Potentials, Age Factors, Aging, Analysis of Variance, Animals, Biophysics, Circadian Rhythm, Electric Stimulation, Electroencephalography, Electromyography, Male, Mice, Inbred C57BL, Motor Activity, Neurons, Periodicity, Sleep, Sleep Deprivation, Suprachiasmatic Nucleus, Wakefulness, Patch-Clamp Techniques, Tetraethylammonium, Potassium Channel Blockers, Mice, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
