The circadian clock and pathology of the ageing brain

Kondratova, Anna A.; Kondratov, Roman V.

doi:10.1038/nrn3208

Cited by 482Circadian rhythm and melatoninGenetics, Aging, and Longevity in Model OrganismsSleep and Wakefulness Research

The circadian clock and pathology of the ageing brain

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Kondratova, Anna A., Kondratov, Roman V.·2012·Nature Reviews Neuroscience

DOI 10.1038/nrn3208PMC PMC3718301

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Abstract

Ageing leads to a functional deterioration of many brain systems, including the circadian clock--an internal time-keeping system that generates ∼24-hour rhythms in physiology and behaviour. Numerous clinical studies have established a direct correlation between abnormal circadian clock functions and the severity of neurodegenerative and sleep disorders. Latest data from experiments in model organisms, gene expression studies and clinical trials imply that dysfunctions of the circadian clock contribute to ageing and age-associated pathologies, thereby suggesting a functional link between the circadian clock and age-associated decline of brain functions. Potential molecular mechanisms underlying this link include the circadian control of physiological processes such as brain metabolism, reactive oxygen species homeostasis, hormone secretion, autophagy and stem cell proliferation.

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Normalization of dysregulated circadian clock may decelerate brain ageing.
“Normalization of the dysregulated circadian clock may decelerate brain ageing.488”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [488]

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Circadian Time-Place Learning in Mice Depends on Cry Genes
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Ketamine Influences CLOCK:BMAL1 Function Leading to Altered Circadian Gene Expression
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Analysis of cellular, transgenic and human models of Huntington's disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathology
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Circadian Abnormalities in Motor Activity in a BAC Transgenic Mouse Model of Huntington’s Disease
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Assessment of the cortisol awakening response: Expert consensus guidelines
Stalder, T., Kirschbaum, C., Kudielka, B. M., Adam, E. K., Pruessner, J. C., Wüst, S., Dockray, S., Smyth, N., Evans, P., Hellhammer, D. H., et al. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.10.010 · Cited by 967 · see citing works
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Sleep in Normal Aging
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SIRT1 Mediates Central Circadian Control in the SCN by a Mechanism that Decays with Aging
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The aging clock: circadian rhythms and later life
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Genomics of circadian rhythms in health and disease
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Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration
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Circadian rhythms and the molecular clock in cardiovascular biology and disease
Crnko, S., Du Pré, B. C., Sluijter, J. P. G., & Van Laake, L. W. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0167-4 · Cited by 499 · see citing works
Circadian rhythm as a therapeutic target
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Sleep and Circadian Rhythm Regulation in Early Parkinson Disease
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Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice
Acosta-Rodríguez, V. A., Rijo‐Ferreira, F., Izumo, M., Xu, P., Wight‐Carter, M., Green, C. B., & Takahashi, J. S. (2022) · Science · doi:10.1126/science.abk0297 · Cited by 361 · see citing works
Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging
Sato, S., Solanas, G., Peixoto, F. O., Bee, L., Symeonidi, A., Schmidt, M. S., Brenner, C., Masri, S., Benitah, S. A., & Sassone‐Corsi, P. (2017) · Cell · doi:10.1016/j.cell.2017.07.042 · Cited by 359 · see citing works
Time-restricted eating for the prevention and management of metabolic diseases
Manoogian, E. N. C., Chow, L. S., Taub, P. R., Laferrère, B., & Panda, S. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab027 · Cited by 344 · see citing works
Dietary restriction and lifespan: lessons from invertebrate models
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Clarifying the role of sleep in depression: A narrative review
Pandi-Perumal, S. R., Monti, J. M., Burman, D., Ramanujam, K., BaHammam, A. S., Spence, D. W., Brown, G. M., & Narashimhan, M. (2020) · Psychiatry Research · doi:10.1016/j.psychres.2020.113239 · Cited by 335 · see citing works
Sleep Disturbance, Cognitive Decline, and Dementia: A Review
Wu, M. N., Rosenberg, P. B., Spira, A. P., & Wennberg, A. M. V. (2017) · Seminars in Neurology · doi:10.1055/s-0037-1604351 · Cited by 310 · see citing works
Cooccurrence and bidirectional prediction of sleep disturbances and depression in older adults: Meta-analysis and systematic review
Bao, Y.-P., Han, Y., Ma, J., Wang, R.-J., Shi, L., Wang, T.-Y., He, J., Yue, J.-L., Shi, J., Tang, X.-D., et al. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.032 · Cited by 275 · see citing works
SIRT6: Novel Mechanisms and Links to Aging and Disease
Tasselli, L., Zheng, W., & Chua, K. F. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.10.002 · Cited by 267 · see citing works
Astrocytes and Aging
Palmer, A. L., & Ousman, S. S. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00337 · Cited by 247 · see citing works
CHRONOTYPE ASSOCIATIONS WITH DEPRESSION AND ANXIETY DISORDERS IN A LARGE COHORT STUDY: Research Article: Chronotypes in Depression and Anxiety
Antypa, N., Vogelzangs, N., Meesters, Y., Schoevers, R., & Penninx, B. W. J. H. (2016) · Depression and Anxiety · doi:10.1002/da.22422 · Cited by 252 · see citing works
The hallmarks of fibroblast ageing
Tigges, J., Krutmann, J., Fritsche, E., Haendeler, J., Schaal, H., Fischer, J. W., Kalfalah, F., Reinke, H., Reifenberger, G., Stühler, K., et al. (2014) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2014.03.004 · Cited by 250 · see citing works
Suprachiasmatic neuron numbers and rest–activity circadian rhythms in older humans
Wang, J. L., Lim, A. S., Chiang, W., Hsieh, W., Lo, M., Schneider, J. A., Buchman, A. S., Bennett, D. A., Hu, K., & Saper, C. B. (2015) · Annals of Neurology · doi:10.1002/ana.24432 · Cited by 217 · see citing works
Highly efficient conversion of superoxide to oxygen using hydrophilic carbon clusters
Samuel, E. L. G., Marcano, D. C., Berka, V., Bitner, B. R., Wu, G., Potter, A., Fabian, R. H., Pautler, R. G., Kent, T. A., Tsai, A.-L., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417047112 · Cited by 214 · see citing works
Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease
Cedernaes, J., Osorio, R. S., Varga, A. W., Kam, K., Schiöth, H. B., & Benedict, C. (2016) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2016.02.002 · Cited by 200 · see citing works
Magnetic field effects in biology from the perspective of the radical pair mechanism
Zadeh-Haghighi, H., & Simon, C. (2022) · Journal of The Royal Society Interface · doi:10.1098/rsif.2022.0325 · Cited by 197 · see citing works
Modelling changes in sleep timing and duration across the lifespan: changes in circadian rhythmicity or sleep homeostasis?
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
Epigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory
Kwapis, J. L., Alaghband, Y., Kramár, E. A., López, A. J., Ciernia, A. V., White, A. O., Shu, G., Rhee, D., Michael, C. M., Montellier, E., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05868-0 · Cited by 162 · see citing works
A model of the mitochondrial basis of bipolar disorder
Morris, G., Walder, K., McGee, S. L., Dean, O. M., Tye, S. J., Maes, M., & Berk, M. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.014 · Cited by 162 · see citing works
Melatonin Regulates Aging and Neurodegeneration through Energy Metabolism, Epigenetics, Autophagy and Circadian Rhythm Pathways
Jenwitheesuk, A., Nopparat, C., Mukda, S., Wongchitrat, P., & Govitrapong, P. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150916848 · Cited by 161 · see citing works
Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases
Ji, S., Xiong, M., Chen, H., Liu, Y., Zhou, L., Hong, Y., Wang, M., Wang, C., Fu, X., & Sun, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01343-5 · Cited by 166 · see citing works
Circadian gene variants in cancer
Kettner, N. M., Katchy, C. A., & Fu, L. (2014) · Annals of Medicine · doi:10.3109/07853890.2014.914808 · Cited by 147 · see citing works
Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease models
Johansson, J. U., Woodling, N. S., Wang, Q., Panchal, M., Liang, X., Trueba-Saiz, A., Brown, H. D., Mhatre, S. D., Loui, T., & Andreasson, K. I. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77487 · Cited by 161 · see citing works
The Circadian System in Alzheimer’s Disease: Disturbances, Mechanisms, and Opportunities
Coogan, A. N., Schutová, B., Husung, S., Furczyk, K., Baune, B. T., Kropp, P. A., Häßler, F., & Thome, J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.11.021 · Cited by 158 · see citing works
BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders
Qiu, P., Jiang, J., Liu, Z., Cai, Y., Huang, T., Wang, Y., Liu, Q., Nie, Y., Liu, F., Cheng, J., et al. (2019) · National Science Review · doi:10.1093/nsr/nwz002 · Cited by 157 · see citing works
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
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Authors: Kondratova, A. A., & Kondratov, R. V.
Affiliations: Cleveland Clinic (US)
Cleveland State University (US)
Corresponding author: Kondratov, Roman V.
ORCID: Kondratova, Anna A.
Kondratov, Roman V.
Venue: Nature Reviews Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2012-03-07
Volume: 13
Issue: 5
Pages: 325-335
ISSN: 1471-003X (ISSN-L)
1471-0048
DOI: 10.1038/nrn3208
PMC: PMC3718301
OpenAlex: W2077676121
Cited by: 482
References: 143
Citations by year: 2026: 23 · 2025: 29 · 2024: 28 · 2023: 24 · 2022: 49 · 2021: 44 · 2020: 41 · 2019: 24 · 2018: 30 · 2017: 48 · 2016: 36 · 2015: 40 · 2014: 26 · 2013: 32 · 2012: 8
FWCI: 3.83
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (R03AG033881, R01AG039547)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords: circadian clock, brain aging, neurodegeneration, sleep disorders, brain metabolism, reactive oxygen species, hormone secretion, autophagy, stem cell proliferation, circadian rhythm
MeSH terms: Aging, Animals, Brain, Circadian Rhythm, Cognition Disorders, Humans, Circadian Clocks

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