Foundations of circadian medicine
Open accessAbstract
The circadian clock is an evolutionarily highly conserved endogenous timing program that structures physiology and behavior according to the time of day. Disruption of circadian rhythms is associated with many common pathologies. The emerging field of circadian medicine aims to exploit the mechanisms of circadian physiology and clock-disease interaction for clinical diagnosis, treatment, and prevention. In this Essay, we outline the principle approaches of circadian medicine, highlight the development of the field in selected areas, and point out open questions and challenges. Circadian medicine has unambiguous health benefits over standard care but is rarely utilized. It is time for clock biology to become an integrated part of translational research.
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Disruption of daily rhythms has been implicated in various health conditions.
“The disruption of these daily rhythms has been implicated in various health conditions, underscoring the importance of maintaining a well‐synchronised circadian clock [9, 10].”
The circadian rhythm is fundamental to nearly every cellular, physiological, and behavioural process in the human body.
“The circadian rhythm is fundamental to nearly every cellular, physiological, and behavioural process in the human body [9].”
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Cites
Transcriptional architecture of the mammalian circadian clock
Takahashi, J. S. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.150 · Cited by 2,639 · cited 3× · see citing works
“The components of the molecular clockwork were successively discovered in different species (in mammals, about a dozen genes are involved) and the molecular mechanism of circadian rhythm generation, the TTFL, was deciphered [14].”
BackgroundDamiola, F., Le Minh, N., Preitner, N., Kornmann, B., Fleury-Olela, F., & Schibler, U. (2000) · Genes & Development · doi:10.1101/gad.183500 · Cited by 2,394 · cited 1× · see citing works
“The dominant natural time signal (or zeitgeber) for the human circadian clock is light, but food signals can also entrain cellular circadian clocks in peripheral tissues [10].”
BackgroundA circadian gene expression atlas in mammals: Implications for biology and medicine
Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E., & Hogenesch, J. B. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408886111 · Cited by 2,304 · cited 1× · see citing works
“We know from mouse experiments that between 5% and 20% of all protein-coding genes are rhythmically expressed in each tissue, and nearly half are rhythmic somewhere in the body [5].”
BackgroundClock Mutants of Drosophila melanogaster
Konopka, R. J., & Benzer, S. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.9.2112 · Cited by 2,287 · cited 1× · see citing works
“In the 1970s, Ron Konopka and Seymour Benzer identified the first clock gene mutants in the fruit fly Drosophila, thus establishing a genetic basis for behavior [11].”
BackgroundEpidemiology of the human circadian clock
Roenneberg, T., Kuehnle, T., Juda, M., Kantermann, T., Allebrandt, K., Gordijn, M., & Merrow, M. (2007) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2007.07.005 · Cited by 1,545 · cited 2× · see citing works
“There is a striking age dependency of chronotype: Children on average start as early types but become later and later during puberty, whereas adults become earlier and earlier with increasing age [17].”
BackgroundAn h <i>Per2</i> Phosphorylation Site Mutation in Familial Advanced Sleep Phase Syndrome
Toh, K. L., Jones, C. R., He, Y., Eide, E. J., Hinz, W. A., Virshup, D. M., Ptáček, L. J., & Fu, Y.-H. (2001) · Science · doi:10.1126/science.1057499 · Cited by 1,460 · cited 2× · see citing works
“PLOS Biology | https://doi.org/10.1371/journal.pbio.3001567 March 24, 2022 3 / 13 locomotor output cycles kaput; CRY1, cryptochrome 1; FASPS, familial advanced sleep– wake phase syndrome; MTNR1B, melatonin receptor 1B; RA, rheumatoid arthritis; SCN, suprachiasmatic nucleus; TTFL, transcriptional– translational feedbac…”
BackgroundInfluentialRoenneberg, T., Allebrandt, K. V., Merrow, M., & Vetter, C. (2012) · Current Biology · doi:10.1016/j.cub.2012.03.038 · Cited by 1,407 · cited 1× · see citing works
“Social jetlag is associated with increased alcohol and cigarette consumption [37] and a higher prevalence of obesity [37], diabetes, cardiovascular diseases, and cancer [38].”
BackgroundNight-Shift Work and Risk of Colorectal Cancer in the Nurses' Health Study
Schernhammer, E. S., Laden, F., Speizer, F. E., Willett, W. C., Hunter, D. J., Kawachi, I. I., Fuchs, C. S., & Colditz, G. A. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/95.11.825 · Cited by 837 · cited 1× · see citing works
“For example, the large epidemiological Nurses’ Health Study showed that cancer is associated with shift work and circadian rhythm disruption [33].”
BackgroundAschoff, J. (1965) · Science · doi:10.1126/science.148.3676.1427 · Cited by 752 · see citing works
Circadian clocks and insulin resistance
Stenvers, D. J., Scheer, F. A. J. L., Schrauwen, P., la Fleur, S. E., & Kalsbeek, A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0122-1 · Cited by 733 · cited 1× · see citing works
“In type 2 diabetes, circadian regulation of insulin secretion is impaired [48] and shifted eating patterns correlate with increased body mass index [49], in line with disrupted gut microbiota rhythms [8].”
BackgroundCircadian Gene Bmal1 Regulates Diurnal Oscillations of Ly6C hi Inflammatory Monocytes
Nguyen, K. D., Fentress, S. J., Qiu, Y., Yun, K., Cox, J. S., & Chawla, A. (2013) · Science · doi:10.1126/science.1240636 · Cited by 647 · cited 1× · see citing works
“Bmal1 knockout in various tissues leads to phenotypes such as hypoglycemia and dyslipidemia (in the liver) [22], metabolic inefficiency and impaired triglyceride biosynthesis (in the muscle) [23], obesity (in adipose tissue) [24], or increased inflammation and insulin resistance (in myeloid cells) [25].”
BackgroundThe human circadian metabolome
Dallmann, R., Viola, A. U., Tarokh, L., Cajochen, C., & Brown, S. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114410109 · Cited by 566 · cited 1× · see citing works
“This ubiquity of circadian rhythms is reflected at the protein [6] and metabolite levels [7].”
BackgroundDysregulation of inflammatory responses by chronic circadian disruption
Castanon-Cervantes, O., Wu, M., Ehlen, J. C., Paul, K., Gamble, K. L., Johnson, R. L., Besing, R. C., Menaker, M., Gewirtz, A. T., & Davidson, A. J. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001026 · Cited by 542 · cited 1× · see citing works
“Exposing mice to a chronodisruptive environment such as repeated shifts in the light–dark cycle (simulating shift work or jetlag) increases mortality in aged animals [29], promotes tumor growth [30] and autoimmune processes [31], and dysregulates inflammatory responses [32].”
BackgroundCircadian Mechanisms in Medicine
Allada, R., & Bass, J. (2021) · New England Journal of Medicine · doi:10.1056/nejmra1802337 · Cited by 519 · cited 1× · see citing works
“In summary, overwhelming evidence indicates that the circadian clock is essential for health while its disruption causes pathologies [1].”
BackgroundCircadian rhythm as a therapeutic target
Ruan, W., Yuan, X., & Eltzschig, H. K. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00109-w · Cited by 501 · cited 1× · see citing works
“This variation is explained by daily rhythms in pharmacokinetics and pharmacodynamics of most short-lived drugs [2,50,54].”
BackgroundIdentification of Small Molecule Activators of Cryptochrome
Hirota, T., Lee, J. W., John, P. C. S., Sawa, M., Iwaisako, K., Noguchi, T., Pongsawakul, P. Y., Sonntag, T., Welsh, D. K., Brenner, D. A., et al. (2012) · Science · doi:10.1126/science.1223710 · Cited by 500 · cited 1× · see citing works
“For example, molecules that stabilize the clock protein cryptochrome 1 (CRY1) improve glucose tolerance in obese mice [64,65], while inhibiting casein kinase 1δ (CK1δ) prolongs clock period and may be used to treat (F)ASPS [66].”
BackgroundRestoration of circadian behavioural rhythms by gene transfer in Drosophila
Bargiello, T. A., Jackson, F. R., & Young, M. W. (1984) · Nature · doi:10.1038/312752a0 · Cited by 498 · cited 1× · see citing works
“With the cloning of the fly period (per) gene in the 1980s, the molecular biology era of chronobiology began [12,13].”
BackgroundObesity in mice with adipocyte-specific deletion of clock component Arntl
Paschos, G. K., Ibrahim, S., Song, W.-L., Kunieda, T., Grant, G., Reyes, T. M., Bradfield, C. A., Vaughan, C. H., Eiden, M., Masoodi, M., et al. (2012) · Nature Medicine · doi:10.1038/nm.2979 · Cited by 465 · cited 1× · see citing works
“Bmal1 knockout in various tissues leads to phenotypes such as hypoglycemia and dyslipidemia (in the liver) [22], metabolic inefficiency and impaired triglyceride biosynthesis (in the muscle) [23], obesity (in adipose tissue) [24], or increased inflammation and insulin resistance (in myeloid cells) [25].”
BackgroundChronic jet-lag increases mortality in aged mice
Davidson, A. J., Sellix, M. T., Daniel, J., Yamazaki, S., Menaker, M., & Block, G. D. (2006) · Current Biology · doi:10.1016/j.cub.2006.09.058 · Cited by 427 · see citing works
Host Circadian Clock as a Control Point in Tumor Progression
Filipski, E. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.9.690 · Cited by 413 · cited 1× · see citing works
“Anatomical ablation of the SCN pacemaker in rodents is associated with changes in intestinal immune cells and microbiota [26], increased adiposity [27], and tumor growth [28].”
BackgroundButtgereit, F., Doering, G., Schaeffler, A., Witte, S., Sierakowski, S., Gromnica‐Ihle, E., Jeka, S., Krueger, K., Szechiński, J., & Alten, R. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60132-4 · Cited by 406 · cited 2× · see citing works
“prednisone in the evening (with drug release during the second half of the night) reduces peak nocturnal interleukin-6 levels, thus positively affecting clinical parameters [42].”
BackgroundZehring, W. A., Wheeler, D. A., Reddy, P., Konopka, R. J., Kyriacou, C. P., Rosbash, M., & Hall, J. C. (1984) · Cell · doi:10.1016/0092-8674(84)90015-1 · Cited by 393 · cited 1× · see citing works
“With the cloning of the fly period (per) gene in the 1980s, the molecular biology era of chronobiology began [12,13].”
BackgroundRobles, M. S., Cox, J., & Mann, M. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004047 · Cited by 383 · cited 1× · see citing works
“This ubiquity of circadian rhythms is reflected at the protein [6] and metabolite levels [7].”
BackgroundSundowning and Circadian Rhythms in Alzheimer’s Disease
Volicer, L., Harper, D. G., Manning, B. C., Goldstein, R., & Satlin, A. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.5.704 · Cited by 382 · cited 1× · see citing works
“The “sundowning syndrome” in patients with Alzheimer’s disease is a prominent example [43].”
BackgroundCircadian rhythms and the gut microbiota: from the metabolic syndrome to cancer
Bishehsari, F., Voigt, R. M., & Keshavarzian, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-00427-4 · Cited by 378 · cited 1× · see citing works
“It disrupts natural rhythms of the gut microbiota, thus increasing the risk of inflammatory bowel disease [36].”
BackgroundMedicine in the Fourth Dimension
Cederroth, C. R., Albrecht, U., Bass, J. T., Brown, S. A., Dyhrfjeld‐Johnsen, J., Gachon, F., Green, C. B., Hastings, M. H., Helfrich‐Förster, C., Hogenesch, J. B., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.019 · Cited by 363 · cited 2× · see citing works
“This variation is explained by daily rhythms in pharmacokinetics and pharmacodynamics of most short-lived drugs [2,50,54].”
BackgroundImpact of circadian disruption on glucose metabolism: implications for type 2 diabetes
Mason, I. C., Qian, J., Adler, G. K., & Scheer, F. A. J. L. (2020) · Diabetologia · doi:10.1007/s00125-019-05059-6 · Cited by 359 · cited 1× · see citing works
“In laboratory studies in humans, circadian misalignment leads to increased blood pressure, increased ghrelin, and decreased leptin levels, as well as reduced insulin sensitivity in skeletal muscle (for a review, see [39]).”
BackgroundTiming of expression of the core clock gene Bmal1 influences its effects on aging and survival
Yang, G., Chen, L., Grant, G. R., Paschos, G. K., Song, W., Musiek, E. S., Lee, V., McLoughlin, S. C., Großer, T., Cotsarelis, G., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad3305 · Cited by 317 · cited 1× · see citing works
“Genetic deletion of the essential clock gene Bmal1 [14] in mice leads to various pathologies, including hyperglycemia, hyperlipidemia, increased inflammation, and premature aging [21].”
BackgroundMontaigne, D., Marechal, X., Modine, T., Coisne, A., Mouton, S., Fayad, G., Ninni, S., Klein, C., Ortmans, S., Seunes, C., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(17)32132-3 · Cited by 315 · cited 1× · see citing works
“major adverse cardiovascular events are lower when aortic valve replacement is performed in the afternoon compared with morning surgeries, probably because myocardial tolerance to ischemia-reperfusion is better at this time of day [56].”
BackgroundSleep, circadian rhythms and health
Foster, R. G. (2020) · Interface Focus · doi:10.1098/rsfs.2019.0098 · Cited by 286 · cited 1× · see citing works
“The circadian system is tightly linked to sleep [20].”
BackgroundShiftwork and Metabolic Risk Factors of Cardiovascular Disease
Ha, M., & Park, J. (2005) · Journal of Occupational Health · doi:10.1539/joh.47.89 · Cited by 276 · cited 1× · see citing works
“Shift work further increases the risk of dyslipidemia and hypertension, type 2 diabetes, heart attacks, and multiple sclerosis [34,35].”
BackgroundArrhythmic Gut Microbiome Signatures Predict Risk of Type 2 Diabetes
Reitmeier, S., Kießling, S., Clavel, T., List, M., Almeida, E. L., Ghosh, T. S., Neuhaus, K., Grallert, H., Linseisen, J., Skurk, T., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.06.004 · Cited by 274 · cited 2× · see citing works
“Recent data reveal that even the composition of the gut microbiota exhibits prominent circadian rhythms [8].”
BackgroundGorbacheva, V., Kondratov, R. V., Zhang, R., Cherukuri, S., Gudkov, A. V., Takahashi, J. S., & Antoch, M. P. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409897102 · Cited by 270 · see citing works
High-accuracy determination of internal circadian time from a single blood sample
Wittenbrink, N., Ananthasubramaniam, B., Münch, M. Y., Koller, B., Maier, B., Weschke, C., Bes, F., de Zeeuw, J., Nowozin, C., Wahnschaffe, A., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120874 · Cited by 260 · cited 1× · see citing works
“Recently, more practicable biomarkers have been suggested that use single blood or tissue samples instead of time series analyses, which may allow the determination of chronotype in larger cohorts [69].”
BackgroundSelf-citationCYCLOPS reveals human transcriptional rhythms in health and disease
Anafi, R. C., Francey, L. J., Hogenesch, J. B., & Kim, J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1619320114 · Cited by 252 · see citing works
Genetic basis of chronotype in humans: insights from three landmark GWAS
Kalmbach, D. A., Schneider, L. D., Cheung, J., Bertrand, S. J., Kariharan, T., Pack, A. I., & Gehrman, P. R. (2017) · Sleep · doi:10.1093/sleep/zsw048 · Cited by 243 · cited 1× · see citing works
“Chronotype is approximately normally distributed within the population, indicating polygenic traits [18].”
BackgroundRuben, M. D., Smith, D. F., FitzGerald, G. A., & Hogenesch, J. B. (2019) · Science · doi:10.1126/science.aax7621 · Cited by 239 · cited 1× · see citing works
“This variation is explained by daily rhythms in pharmacokinetics and pharmacodynamics of most short-lived drugs [2,50,54].”
BackgroundAdafer, R., Messaadi, W., Meddahi, M., Patey, A., Haderbache, A., Bayen, S., & Messaadi, N. (2020) · Nutrients · doi:10.3390/nu12123770 · Cited by 233 · cited 1× · see citing works
“Time-restricted eating, in which food consumption is limited to a window of 8 to 12 hours per day (without caloric restriction), improves glucose regulation, triglyceride levels, blood pressure, and various quality of life measures [62].”
BackgroundQian, D. C., Kleber, T., Brammer, B., Xu, K. M., Switchenko, J. M., Janopaul-Naylor, J. R., Zhong, J., Yushak, M. L., Harvey, R. D., Paulos, C. M., et al. (2021) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00546-5 · Cited by 223 · cited 1× · see citing works
“Timed immunotherapy in patients with melanoma has proven superior to standard therapy in terms of adverse effects and survival [55].”
BackgroundLight and the Human Circadian Clock
Roenneberg, T., Kantermann, T., Juda, M., Vetter, C., & Allebrandt, K. V. (2013) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25950-0_13 · Cited by 220 · cited 1× · see citing works
“Interactions between genetic disposition, age, sex hormones, and light exposure (intensity, duration, and timing) determines the so-called chronotype [16].”
BackgroundLight-entrained and brain-tuned circadian circuits regulate ILC3s and gut homeostasis
Godinho‐Silva, C., Domingues, R. G., Rendas, M. A., Raposo, B., Ribeiro, H., da Silva, J. A., Vieira, A. I. S., Costa, R. M., Barbosa‐Morais, N. L., Carvalho, T., et al. (2019) · Nature · doi:10.1038/s41586-019-1579-3 · Cited by 220 · cited 1× · see citing works
“Anatomical ablation of the SCN pacemaker in rodents is associated with changes in intestinal immune cells and microbiota [26], increased adiposity [27], and tumor growth [28].”
BackgroundMood, the Circadian System, and Melanopsin Retinal Ganglion Cells
Ospri, L. L., Prusky, G. T., & Hattar, S. S. (2017) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-072116-031324 · Cited by 179 · cited 1× · see citing works
“In the retina, light is perceived by rods, cones, and blue-light sensitive ganglion cells expressing the photopigment melanopsin to synchronize the SCN clock with the environment [15].”
BackgroundThe Suprachiasmatic Nucleus Controls Circadian Energy Metabolism and Hepatic Insulin Sensitivity
Coomans, C. P., van den Berg, S. A. A., Lucassen, E. A., Houben, T., Pronk, A. C. M., van der Spek, R. D., Kalsbeek, A., Biermasz, N. R., Willems van Dijk, K., Romijn, J. A., et al. (2013) · Diabetes · doi:10.2337/db12-0507 · Cited by 173 · cited 1× · see citing works
“Anatomical ablation of the SCN pacemaker in rodents is associated with changes in intestinal immune cells and microbiota [26], increased adiposity [27], and tumor growth [28].”
BackgroundSunset time and the economic effects of social jetlag: evidence from US time zone borders
Giuntella, O., & Mazzonna, F. (2019) · Journal of Health Economics · doi:10.1016/j.jhealeco.2019.03.007 · Cited by 165 · cited 1× · see citing works
“Social jetlag is associated with increased alcohol and cigarette consumption [37] and a higher prevalence of obesity [37], diabetes, cardiovascular diseases, and cancer [38].”
BackgroundRecent advances in circadian rhythms in cardiovascular system
Chen, L., & Yang, G. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00071 · Cited by 157 · cited 1× · see citing works
“Epidemiological studies show a steep increase in the incidence of heart attacks and strokes in the morning hours [40].”
BackgroundLewis, P., Korf, H., Kuffer, L., Groß, J. V., & Erren, T. C. (2018) · BMJ Open Sport & Exercise Medicine · doi:10.1136/bmjsem-2018-000443 · Cited by 156 · cited 1× · see citing works
“Exercise can phase-shift the human clock in a similar manner to light and enhance circadian amplitude of rest–activity cycles, body temperature, and muscle strength [63].”
BackgroundDyar, K. A., Hubert, M. J., Mir, A. A., Ciciliot, S., Lutter, D., Greulich, F., Quagliarini, F., Kleinert, M., Fischer, K., Eichmann, T. O., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2005886 · Cited by 154 · cited 1× · see citing works
“Bmal1 knockout in various tissues leads to phenotypes such as hypoglycemia and dyslipidemia (in the liver) [22], metabolic inefficiency and impaired triglyceride biosynthesis (in the muscle) [23], obesity (in adipose tissue) [24], or increased inflammation and insulin resistance (in myeloid cells) [25].”
BackgroundClocking in: chronobiology in rheumatoid arthritis
Buttgereit, F., Smolen, J. S., Coogan, A. N., & Cajochen, C. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.31 · Cited by 137 · cited 1× · see citing works
“Patients with rheumatoid arthritis (RA) are particularly affected by joint stiffness and pain in the morning hours, an aftereffect of a nocturnal increase in proinflammatory cytokines [41].”
BackgroundThe arrival of circadian medicine
Panda, S. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0142-x · Cited by 135 · cited 1× · see citing works
“Many zeitgebers known to influence the circadian system, such as light, food, melatonin, and exercise, have been used for this purpose [59].”
BackgroundPan, X., Bradfield, C. A., & Hussain, M. M. (2016) · Nature Communications · doi:10.1038/ncomms13011 · Cited by 132 · cited 1× · see citing works
“Bmal1 knockout in various tissues leads to phenotypes such as hypoglycemia and dyslipidemia (in the liver) [22], metabolic inefficiency and impaired triglyceride biosynthesis (in the muscle) [23], obesity (in adipose tissue) [24], or increased inflammation and insulin resistance (in myeloid cells) [25].”
BackgroundMammalian circadian systems: Organization and modern life challenges
Finger, A., & Kramer, A. (2021) · Acta Physiologica · doi:10.1111/apha.13548 · Cited by 117 · cited 3× · see citing works
“Through a variety of routes, the SCN synchronizes the many molecular clocks in other brain areas and in peripheral organs [3,4].”
BackgroundSelf-citationCoupled network of the circadian clocks: a driving force of rhythmic physiology
Finger, A., Dibner, C., & Kramer, A. (2020) · FEBS Letters · doi:10.1002/1873-3468.13898 · Cited by 99 · cited 2× · see citing works
“Through a variety of routes, the SCN synchronizes the many molecular clocks in other brain areas and in peripheral organs [3,4].”
BackgroundSelf-citationLate-night salivary cortisol measurement in the diagnosis of Cushing’s syndrome
Carroll, T., Raff, H., & Findling, J. W. (2008) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0837 · Cited by 97 · cited 1× · see citing works
“For example, for the diagnosis of Cushing’s syndrome, which is characterized by hypercortisolemia, cortisol levels should be determined in the evening when endogenous cortisol production is at its trough [57], while adrenal insufficiency should be diagnosed in the morning when cortisol normally peaks [58].”
BackgroundChronotherapy: Intuitive, Sound, Founded…But Not Broadly Applied
Selfridge, J. M., Gotoh, T., Schiffhauer, S., Liu, J., Stauffer, P. E., Li, A., Capelluto, D. G. S., & Finkielstein, C. V. (2016) · Drugs · doi:10.1007/s40265-016-0646-4 · Cited by 84 · see citing works
Circadian and Sleep Dysfunctions in Neurodegenerative Disorders—An Update
Fifel, K., & Videnović, A. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.627330 · Cited by 68 · cited 1× · see citing works
“In patients with neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, or Huntington’s disease, sleep–wake behavior, melatonin secretion, and clock gene expression rhythms are all disrupted [45].”
BackgroundSleep, circadian rhythms, and schizophrenia
Cosgrave, J., Wulff, K., & Gehrman, P. (2018) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000419 · Cited by 60 · cited 1× · see citing works
“This holds true for schizophrenia spectrum and several other psychiatric disorders [46].”
BackgroundCircadian clock genes as promising therapeutic targets for autoimmune diseases
Xiang, K., Xu, Z., Hu, Y., He, Y.-S., Wu, G., Li, T., Wang, X., Ding, L., Zhang, Q., Tao, S., et al. (2021) · Autoimmunity Reviews · doi:10.1016/j.autrev.2021.102866 · Cited by 57 · cited 1× · see citing works
“In patients with autoimmune diseases, daily rhythms in rest–activity, hormone, and cytokine levels, as well as molecular clock rhythms are disrupted [47].”
BackgroundA Review of the Relationship between Night Eating Syndrome and Body Mass Index
Bruzas, M. B., & Allison, K. C. (2019) · Current Obesity Reports · doi:10.1007/s13679-019-00331-7 · Cited by 56 · cited 1× · see citing works
“In type 2 diabetes, circadian regulation of insulin secretion is impaired [48] and shifted eating patterns correlate with increased body mass index [49], in line with disrupted gut microbiota rhythms [8].”
BackgroundChen, Z. (2012) · Oncology Reports · doi:10.3892/or.2012.1688 · Cited by 52 · cited 1× · see citing works
“Exposing mice to a chronodisruptive environment such as repeated shifts in the light–dark cycle (simulating shift work or jetlag) increases mortality in aged animals [29], promotes tumor growth [30] and autoimmune processes [31], and dysregulates inflammatory responses [32].”
BackgroundReiter, A. M., Sargent, C., & Roach, G. D. (2020) · Chronobiology International · doi:10.1080/07420528.2020.1809443 · Cited by 43 · cited 1× · see citing works
“Chronotype is traditionally determined by questionnaires, actigraphy, or by determining the timing of the evening rise in melatonin levels in blood or saliva [68].”
BackgroundThe Liver Circadian Clock Modulates Biochemical and Physiological Responses to Metformin
Henriksson, E., Huber, A., Soto, E., Kriebs, A., Vaughan, M. E., Duglan, D., Chan, A. B., Papp, S. J., Nguyen, M., Afetian, M. E., et al. (2017) · Journal of Biological Rhythms · doi:10.1177/0748730417710348 · Cited by 36 · see citing works
Light therapy: a new option for neurodegenerative diseases
Liu, Y., Gong, S., Xia, S.-T., Wang, Y., Hao, P., Shen, Y., & Liu, C. (2020) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001301 · Cited by 30 · cited 1× · see citing works
“Light therapy is a widely used adjunct therapy in sleep–wake rhythm and psychiatric disorders (such as depression and bipolar disorder [60]), but also in neurodegenerative disorders (such as Alzheimer’s disease and Parkinson’s disease [61]).”
BackgroundRecent Advances in the Development of Casein Kinase 1 Inhibitors
Li, S., Dong, Y., & Liu, Z. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327666200713185413 · Cited by 23 · cited 1× · see citing works
“For example, molecules that stabilize the clock protein cryptochrome 1 (CRY1) improve glucose tolerance in obese mice [64,65], while inhibiting casein kinase 1δ (CK1δ) prolongs clock period and may be used to treat (F)ASPS [66].”
BackgroundRotating night shift work and risk of multiple sclerosis in the Nurses’ Health Studies
Papantoniou, K., MASSA, J. S., Devore, E. E., Munger, K. L., Chitnis, T., Ascherio, A., & Schernhammer, E. S. (2019) · Occupational and Environmental Medicine · doi:10.1136/oemed-2019-106016 · Cited by 21 · cited 1× · see citing works
“Shift work further increases the risk of dyslipidemia and hypertension, type 2 diabetes, heart attacks, and multiple sclerosis [34,35].”
BackgroundDeota, S., & Panda, S. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa691 · Cited by 21 · cited 1× · see citing works
“For example, molecules that stabilize the clock protein cryptochrome 1 (CRY1) improve glucose tolerance in obese mice [64,65], while inhibiting casein kinase 1δ (CK1δ) prolongs clock period and may be used to treat (F)ASPS [66].”
BackgroundSerum Morning Cortisol as A Screening Test for Adrenal Insufficiency
Montes‐Villarreal, J., Pérez-Arredondo, L. A., Rodríguez‐Gutiérrez, R., González-Colmenero, A. D., Solís, R. C., González‐González, J. G., & Mancillas‐Adame, L. G. (2019) · Endocrine Practice · doi:10.4158/ep-2019-0327 · Cited by 18 · cited 1× · see citing works
“For example, for the diagnosis of Cushing’s syndrome, which is characterized by hypercortisolemia, cortisol levels should be determined in the evening when endogenous cortisol production is at its trough [57], while adrenal insufficiency should be diagnosed in the morning when cortisol normally peaks [58].”
BackgroundPatient-centered lighting environments to improve health care in the intensive care unit
Luetz, A., Piazena, H., Weiß, B., Finke, A., Willemeit, T., & Spies, C. (2016) · Clinical Health Promotion - Research and Best Practice for patients staff and community · doi:10.29102/clinhp.16002 · Cited by 14 · cited 1× · see citing works
“In addition, since current ICUs do not provide adequate light settings, we have implemented a novel concept at Charité –Universitätsmedizin Berlin, consisting of a light ceiling for each experimental ICU bed that extends from the head above the patient to the patient’s feet [67].”
MethodSelf-citationUnderstanding the Concept of Chronotherapeutics in the Management of Diabetes Mellitus
Kashyap, S., Bala, R., & Behl, T. (2020) · Current Diabetes Reviews · doi:10.2174/1573399816666201022120825 · Cited by 9 · cited 1× · see citing works
“On the other hand, the “dawn phenomenon” in patients with diabetes, characterized by abnormally high fasting blood glucose levels due to impaired insulin secretion, is another example for an aggravation of disease symptoms during the morning [44].”
BackgroundLight therapy for mood disorders.
Bais, B., Hoogendijk, W., & den Berg, M. P. L.-V. (2021) · Handbook of Clinical Neurology · doi:10.1016/b978-0-12-819973-2.00004-6 · Cited by 8 · cited 1× · see citing works
“Light therapy is a widely used adjunct therapy in sleep–wake rhythm and psychiatric disorders (such as depression and bipolar disorder [60]), but also in neurodegenerative disorders (such as Alzheimer’s disease and Parkinson’s disease [61]).”
BackgroundToth, L. A., Trammell, R. A., Liberati, T. A., Verhulst, S., Hart, M. L., Moskowitz, J. E., & Franklin, C. L. (2017) · PubMed Central · Cited by 7 · see citing works
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Defining the age-dependent and tissue-specific circadian transcriptome in male mice
Wolff, C. A., Gutierrez‐Monreal, M. A., Meng, L., Zhang, X., Douma, L. G., Costello, H. M., Douglas, C. M., Ebrahimi, E., Pham, A. T., Oliveira, A. C. D. S., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2022.111982 · Cited by 153 · see citing works
“26,27 The RNA-seq sensitivity enabled the detection of cellular markers specific to cell types and nuclei, for example, Vip and Nms (SCN), Agrp, Npy and Pomc (arcuate nucleus), Hcrt (lateral hypothalamic area), Gfap (astrocytes), and Aif1 (microglia).”
Chronobiology and Chronomedicine
Gonçalves, C. F., & Meng, Q. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781839167553 · Cited by 118 · see citing works
Circadian regulation of liver function: from molecular mechanisms to disease pathophysiology
Bolshette, N. B., Ibrahim, H., Reinke, H., & Asher, G. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00792-1 · Cited by 99 · see citing works
“Hence, a circadian clock that functions in synchrony with the environment and throughout the body is considered to confer health benefits 4,5 .”
BackgroundKeeping an eye on circadian time in clinical research and medicine
Klerman, E. B., Brager, A. J., Carskadon, M. A., Depner, C. M., Foster, F., Goel, N., Harrington, M. E., Holloway, P. M., Knauert, M. P., LeBourgeois, M. K., et al. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.1131 · Cited by 96 · see citing works
Self-citationWearables in Chronomedicine and Interpretation of Circadian Health
Gubin, D. G., Weinert, D., Stefani, O., Otsuka, K., Borisenkov, M. F., & Cornélissen, G. (2025) · Diagnostics · doi:10.3390/diagnostics15030327 · Cited by 72 · see citing works
Circadian rhythm disruption in critically ill patients
Felten, M., Dame, C., Lachmann, G., Spies, C., Rubarth, K., Balzer, F., Kramer, A., & Witzenrath, M. (2023) · Acta Physiologica · doi:10.1111/apha.13962 · Cited by 56 · see citing works
Self-citationLearning from circadian rhythm to transform cancer prevention, prognosis, and survivorship care
Zhu, X., Maier, G., & Panda, S. (2023) · Trends in cancer · doi:10.1016/j.trecan.2023.11.002 · Cited by 55 · see citing works
Circadian rhythms in cardiovascular disease
Kelters, I. R., Koop, Y., Young, M. E., Daiber, A., & Laake, L. W. V. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf367 · Cited by 60 · see citing works
“170 However, a lack of awareness among medical professionals limits the integration of circadian strategies into routine patient care.”
Dysfunction of circadian and sleep rhythms in the early stages of Alzheimer's disease
Rigat, L., Ouk, K., Kramer, A., & Priller, J. (2023) · Acta Physiologica · doi:10.1111/apha.13970 · Cited by 50 · see citing works
Self-citationEffects of Healthy Lifestyles on Chronic Diseases: Diet, Sleep and Exercise
Oster, H., & Chaves, I. (2023) · Nutrients · doi:10.3390/nu15214627 · Cited by 53 · see citing works
Self-citationStroke in the Time of Circadian Medicine
Mergenthaler, P., Balami, J. S., Neuhaus, A. A., Mottahedin, A., Albers, G. W., Rothwell, P. M., Saver, J. L., Young, M. E., & Buchan, A. M. (2024) · Circulation Research · doi:10.1161/circresaha.124.323508 · Cited by 42 · see citing works
Circadian biology to advance therapeutics for mood disorders
Bhatnagar, A., Murray, G., & Ray, S. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.07.008 · Cited by 40 · see citing works
Crosstalk Between Aging, Circadian Rhythm, and Melatonin
Verma, A. K., Khan, M. I., Ashfaq, F., & Rizvi, S. I. (2023) · Rejuvenation Research · doi:10.1089/rej.2023.0047 · Cited by 33 · see citing works
Jia, M., Luo, A., Wei, M., Zhang, Y., Wu, T., & Chen, N. (2025) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2025.102123 · Cited by 35 · see citing works
de Assis, L. V. M., Demir, M., & Oster, H. (2023) · Acta Physiologica · doi:10.1111/apha.13915 · Cited by 32 · see citing works
Self-citationChronobiology of Parkinson's disease: Past, present and future
Asadpoordezaki, Z., Coogan, A. N., & Henley, B. M. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15859 · Cited by 31 · see citing works
Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping
Ector, C., Schmal, C., Didier, J., Landtsheer, S. D., Finger, A., Müller-Marquardt, F., Schulte, J. H., Sauter, T., Keilholz, U., Herzel, H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51611-3 · Cited by 27 · see citing works
“The critical factor in the design of future chronotherapeutic treatments may be not only the sensitivity of cancer cells but rather the differential time-of-day sensitivity between cancer and non-malignant tissues 26 .”
BackgroundSelf-citationCircadian de(regulation) in physiology: implications for disease and treatmentPreprint
de Assis, L. V. M., & Kramer, A. (2024) · Genes & Development · doi:10.1101/gad.352180.124 · Cited by 27 · see citing works
Self-citationGubin, D. G., Neroev, V. V., Malishevskaya, Т. N., Kolomeichuk, S. N., Weinert, D., Yuzhakova, N., Nelaeva, A. A., Filippova, Y., & Cornélissen, G. (2022) · Applied Sciences · doi:10.3390/app12136374 · Cited by 23 · see citing works
Jiang, S., Fu, Y., & Cheng, H. W. (2023) · Poultry Science · doi:10.1016/j.psj.2023.103162 · Cited by 23 · see citing works
Yan, Y., Su, L., Huang, S., He, Q., Lu, J., Luo, H., Xu, K., Yang, G., Huang, S., & Chi, H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1444426 · Cited by 23 · see citing works
“This synchronization occurs through neural and humoral pathways, maintaining consistent phase relationships within the circadian system (11).”
BackgroundUnderstanding the role of chronopharmacology for drug optimization: what do we know?
Fujimura, A., & Ushijima, K. (2023) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2023.2233438 · Cited by 20 · see citing works
“Circadian rhythm influences not only the absorption of drugs but also their pharmacological effects [1,2,8].”
BackgroundInfluentialDisruption of day‐to‐night changes in circadian gene expression with chronic tendinopathy
Yeung, C. C., Svensson, R. B., Yurchenko, K., Malmgaard‐Clausen, N. M., Tryggedsson, I., Lendal, M. S., Jokipii‐Utzon, A., Olesen, J. L., Lu, Y., Kadler, K. E., et al. (2023) · The Journal of Physiology · doi:10.1113/jp284083 · Cited by 19 · see citing works
Cryptochromes in mammals: a magnetoreception misconception?
Zhang, L., & Malkemper, E. P. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1250798 · Cited by 19 · see citing works
“, 2021b), are emerging fields of large potential (Kramer et al., 2022).”
BackgroundCircadian medicine for aging attenuation and sleep disorders: Prospects and challenges
Banerjee, S., & Ray, S. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102387 · Cited by 18 · see citing works
Data integration and analysis for circadian medicine
Baum, L., Johns, M., Poikela, M. E., Möller, R., Ananthasubramaniam, B., & Praßer, F. (2023) · Acta Physiologica · doi:10.1111/apha.13951 · Cited by 17 · see citing works
Rhythm is essential: Unraveling the relation between the circadian clock and cancer
Ogunlusi, O., Ghosh, A., Sarkar, M., Carter, K., Davuluri, H., Chakraborty, M., Eckel‐Mahan, K. L., Keene, A. C., Menet, J. S., Bell‐Pedersen, D., et al. (2025) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2025.104632 · Cited by 16 · see citing works
Motiei, M., Abu‐Dawud, R., Relógio, A., & Assaf, C. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105451 · Cited by 14 · see citing works
From bench to bedside and back again: translating circadian science to medicine
Klerman, E. B., Kramer, A., & Zee, P. C. (2023) · Journal of Biological Rhythms · doi:10.1177/07487304221142743 · Cited by 13 · see citing works
“A triad of circadian medicine approaches was recently proposed (Kramer et al., 2022): (a) detecting the clock (e.”
Self-citationNonalcoholic Steatohepatitis Disrupts Diurnal Liver Transcriptome Rhythms in Mice
de Assis, L. V. M., Demir, M., & Oster, H. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2023.05.008 · Cited by 13 · see citing works
“To avoid such complexity, it may be advisable to attempt to stabilize the circadian clock itself and in this way indirectly rectify clock-controlled gene (CCG) output instead of targeting specific genes/processes.(43) Considering”
BackgroundSelf-citationWeger, M., Weger, B. D., & Gachon, F. (2023) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2023.2224554 · Cited by 13 · see citing works
Kramer, A. (2023) · Acta Physiologica · doi:10.1111/apha.13984 · Cited by 12 · see citing works
Self-citationSepúlveda, B., Marín, A., Burrows, R. A., Sepúlveda-Peñaloza, A., & Chamorro, R. (2024) · Current Nutrition Reports · doi:10.1007/s13668-024-00532-0 · Cited by 12 · see citing works
“…findings are relevant for further research, as the relevance of a circadian approach for preventive and treat-ment health outcomes is increasing [104], highlighting the role of the timing of eating for the outcome of preventive and therapeutic dietary interventions based on individual circadian…”
Enhanced Circadian Phase Tracking: A 5-h DLMO Sampling Protocol Using Wearable Data
Lim, D., Choi, S. J., Song, Y. M., Park, H. R., Joo, E. Y., & Kim, J. K. (2025) · Journal of Biological Rhythms · doi:10.1177/07487304251317577 · Cited by 12 · see citing works
Advances in circadian clock regulation of reproduction
Li, Y., Zhang, H., Wang, Y., Li, D., & Chen, H. (2023) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2023.02.008 · Cited by 12 · see citing works
One Health: Circadian Medicine Benefits Both Non-human Animals and Humans Alike
Farag, H. I., Murphy, B. A., Templeman, J. R., Hanlon, C., Joshua, J., Koch, T. G., Niel, L., Shoveller, A. K. K., Bédécarrats, G. Y., Ellison, A., et al. (2024) · Journal of Biological Rhythms · doi:10.1177/07487304241228021 · Cited by 10 · see citing works
Clocking Epilepsies: A Chronomodulated Strategy-Based Therapy for Rhythmic Seizures
Sun, S., & Wang, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24044223 · Cited by 12 · see citing works
Kervezee, L., Dashti, H. S., Pilz, L. K., Skarke, C., & Ruben, M. D. (2024) · PLOS Digital Health · doi:10.1371/journal.pdig.0000511 · Cited by 9 · see citing works
Dashti, H. S., Leong, A., Mogensen, K. M., Annambhotla, M., Li, P., Deng, H., Carey, A. N., Burns, D. L., Winkler, M. F., Compher, C. W., et al. (2023) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2023.11.016 · Cited by 9 · see citing works
“Circadian medicine aims to leverage circadian physiology and the interactions between behaviors and biologic rhythms for the prevention, diagnosis, and treatment of diseases [1].”
BackgroundIt’s about time: circadian medicine in the intensive care unit
Luetz, A., Spies, C., & Kervezee, L. (2023) · Intensive Care Medicine · doi:10.1007/s00134-023-07297-0 · Cited by 9 · see citing works
Self-citationEditorial: Chrononutrition and health
Konstantinidou, V., & Jamshed, H. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1516940 · Cited by 8 · see citing works
The structural and functional roles of the flavin cofactor FAD in mammalian cryptochromes
Calloni, G., & Vabulas, R. M. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1081661 · Cited by 7 · see citing works
“Disruption of circadian rhythms have been associated with several pathologies and there are considerable efforts underway to exploit circadian mechanisms for diagnosis, treatment, and prevention of diseases (Kramer et al., 2022).”
BackgroundGutu, N., Ishikuma, H., Ector, C., Keilholz, U., Herzel, H., & Granada, A. E. (2025) · Communications Biology · doi:10.1038/s42003-025-07931-1 · Cited by 7 · see citing works
Can we utilise the circadian clock to target cancer stem cells?
Lian, J.-W., Li, S.-Y., Clarke, R. B., Howell, S. J., & Meng, Q. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217360 · Cited by 7 · see citing works
The use of prolonged-release melatonin in circadian medicine: a systematic review
CASALE, A. D., Arena, J. F., GIANNETTI, F., Minervino, A., Biggio, G., & Girardi, P. (2024) · Minerva Medica · doi:10.23736/s0026-4806.24.09303-0 · Cited by 6 · see citing works
Evaluation of the Digital Ventilated Cage® system for circadian phenotyping
Tir, S., Foster, F., & Peirson, S. N. (2025) · Scientific Reports · doi:10.1038/s41598-025-87530-6 · Cited by 6 · see citing works
Dai, W., Wen, M., Kalso, E. A., & Palada, V. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106934 · Cited by 6 · see citing works
Murukesu, R. R., Alkaff, Z. A., Bridges, C., & Spitschan, M. (2025) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd016157 · Cited by 5 · see citing works
Circadian rhythm of heart rate and heart rate variability in pregnancy
Rasouli, M., Feli, M., Azimi, I., Haghayegh, S., Sarhaddi, F., Niela‐Vilén, H., Axelin, A., Liljeberg, P., & Rahmani, A. M. (2025) · npj Women s Health · doi:10.1038/s44294-025-00107-6 · Cited by 5 · see citing works
“The patterns of change in HR 6 and HRV 7 follow the circadian rhythm, which has approximately a 24-h cycle and is among the most well-known biological rhythms 8 .”
Circadian disruption in astronauts: Causes, molecular mechanisms, and neurocognitive consequences
Tomaraei, S. N., Ahmed, M., & Nami, M. (2025) · Chronobiology International · doi:10.1080/07420528.2025.2569695 · Cited by 5 · see citing works
“This suggests that spaceflight conditions interfere with post-transcriptional processes, revealing multilayered regulatory challenges (Kramer et al. 2022).”
Timing of diuretic administration effects on urine volume in hospitalized patients
McCullar, K. S., Abbaspour, S., Wang, W., Aguirre, A. D., Westover, M. B., & Klerman, E. B. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2023.1208324 · Cited by 5 · see citing works
“Speci fi cally, this fi eld aims to incorporate knowledge of biological rhythms to increase treatment effectiveness and decrease side effects (Ohdo, 2010; Ruben et al., 2019a; Ruben et al., 2019b; Allada et al., 2021; Kenig et al., 2021; Kramer et al., 2022).”
BackgroundResultThe Option of Chronotherapy of Hypertension
Chrysant, S. G. (2024) · Cardiology in Review · doi:10.1097/crd.0000000000000644 · Cited by 5 · see citing works
Khoshnevis, S., Smolensky, M. H., & Hermida, R. C. (2024) · Chronobiology International · doi:10.1080/07420528.2024.2414878 · Cited by 4 · see citing works
“Circadian chronotherapeutics, a key aspect of the discipline of circadian medicine (Allada et al. 2021; Klerman et al. 2023; Kramer et al. 2022), is defined as the timing of medications and other forms of treatment to the staging of endogenous 24-h rhythms as a means to optimize beneficial and/or…”
Deeb, H., Zieliński, T., & Millar, A. J. (2024) · BMJ Mental Health · doi:10.1136/bmjment-2024-301333 · Cited by 4 · see citing works
“Circadian rhythms, which regulate the sleep-wake cycle and other physiological processes, 8 9 are closely linked to various mental health conditions, including bipolar disorder, depression and are often manifested through symptoms including sleep disturbances.”
Khoshnevis, S., Smolensky, M. H., & Haghayegh, S. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115576 · Cited by 4 · see citing works
Go to bed!: Sleep as a risk factor for adolescent hypertension
Wang, Y. M., Dandoy, C. E., Smith, D. F., & Hogenesch, J. B. (2023) · Progress in Pediatric Cardiology · doi:10.1016/j.ppedcard.2023.101613 · Cited by 5 · see citing works
HairTime: A noninvasive assay for estimating circadian phase from a single hair sample
Maier, B., Pilz, L. K., Özcakir, S., Rahjouei, A., Abdo, A. N., de Zeeuw, J., Kunz, D., & Kramer, A. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2514928123 · Cited by 3 · see citing works
“Nevertheless, the model may already serve as a valuable tool for exploring interindividual differences in peripheral clock function and for tracking responses to interventions aimed at strengthening the circadian system, such as light therapy, mela tonin, or time - restricted eating (38).”
Self-citationTime perception among people living with and without dementia: A scoping review
Gallant, N. L., Russill, C. L., Taylor, N. C., Nakonechny, S., Kohlert, A., & Ewing, K. (2024) · Dementia · doi:10.1177/14713012241257299 · Cited by 3 · see citing works
“…rhythms are associated with increased age and neurodegenerative diseases such as dementia (Lananna & Musiek, 2020; Rigat et al., 2023), and these circadian rhythm dysfunctions can affect one ’ s perceptions of the duration of time intervals and the sequencing of events (Kramer et al., 2022).”
Wei, J., Wu, H., Zheng, Y., Wang, N., Benedict, C., Chen, W., & Tan, X. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111927 · Cited by 3 · see citing works
“Individuals with an evening chronotype are more likely to experience mismatches between social demands and their internal clocks, leading to circadian misalignment [26], which further results in metabolic dysregulations [27].”
The Interplay Between Circadian Clocks and the Tumour Microenvironment in Breast Cancer
Finger, A., Ector, C., & Weaver, V. M. (2026) · Cancers · doi:10.3390/cancers18060925 · Cited by 2 · see citing works
Self-citationMagnitude of parathyroid hormone elevation in primary hyperparathyroidism: Does time of day matter?
Frye, C. C., Sullivan, J., Sanka, S. A., Liu, J., Brunt, L. M., Gillanders, W. E., Brown, T. C., & Pandian, T. K. (2022) · Surgery · doi:10.1016/j.surg.2022.07.051 · Cited by 2 · see citing works
Cardiovascular Implications of Sleep Disorders Beyond Sleep Apnea
Park, J., Yoon, J., Liu, X., Chang, Y., Maiolino, G., Pengo, M. F., Lin, G., & Kwon, Y. (2024) · Current Sleep Medicine Reports · doi:10.1007/s40675-024-00302-y · Cited by 2 · see citing works
“Tailoring treatments and lifestyle interventions based on circadian physiology seems promising [70].”
Time of day shapes the success of a cancer treatment
Gabriel, C. H., & Kramer, A. (2023) · Nature · doi:10.1038/d41586-023-00068-3 · Cited by 2 · see citing works
Self-citationThe interplay between circadian clock and viral infections: A molecular perspective
Kalita, E., Panda, M., & Prajapati, V. K. (2023) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2023.02.009 · Cited by 2 · see citing works
Rajan, R. J., & Palaniappan, D. (2024) · Open Access Research Journal of Biology and Pharmacy · doi:10.53022/oarjbp.2024.10.2.0051 · Cited by 2 · see citing works
Abbaspour, S., Aguirre, A. D., Westover, M. B., & Klerman, E. B. (2022) · medRxiv · doi:10.1101/2022.12.27.22283947 · Cited by 2 · see citing works
Circadian Disturbances and Age‐Related Disorders
Li, P., & Hu, K. (2023) · Advanced Biology · doi:10.1002/adbi.202300405 · Cited by 2 · see citing works
Inactivation of the DREAM complex mimics the molecular benefits of sleepPreprint
Valentim, I. S., Romero-Expósito, F. J., Schwab, K., Bayar, M., Tauassarova, A., Riege, K., Lange, L., Engmann, O., Fischer, M., Olmedo, M., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.26.600859 · Cited by 2 · see citing works
Corrotea-Maltez, C. C., Fernández-Flores, C. V., Gutiérrez-Neira, C. L., Nirrian-Pérez, A. J., Mansilla-Muñoz, J., & Bustos-González, L. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1801194 · Cited by 1 · see citing works
“To mitigate these adverse effects, the emerging field of Circadian Medicine has proposed specific clinical interventions (22, 23).”
Nahtigal, K., Vasle, A. H., Kreft, T., Skubic, C., Mraz, M., Moškon, M., Grošelj, L. D., & Rozman, D. (2026) · Biomolecules · doi:10.3390/biom16071013 · Cited by 1 · see citing works
“Understanding the genetic mechanisms that drive circadian rhythms is crucial, as disruptions in these rhythms are linked to health conditions [11], such as metabolic disorders (e.g., metabolic dysfunction-associated steatotic liver disease [12–14], cardiovascular diseases (e.g., heart failure)…”
Upadhyay, A., Rowland-Chandler, J., Stewart-Wood, J., Pingarron-Cardenas, G., Tokuda, I. T., Webb, A. A. R., & Locke, J. C. W. (2026) · Journal of The Royal Society Interface · doi:10.1098/rsif.2025.0619 · Cited by 2 · see citing works
Areshidze, D. A., Михалева, Л. М., Kakturskiy, L., Kondashevskaya, М. V., Kozlova, M. A., & Chernikov, V. P. (2023) · Ulyanovsk Medico-biological Journal · doi:10.34014/2227-1848-2023-3-151-166 · Cited by 1 · see citing works
Corrotea-Maltez, C. C., Fernández-Flores, C. V., Gutierrez-Neira, C. L., Nirrian-Pérez, A. J., Mansilla-Muñoz, J., & Bustos-González, L. (2025) · medRxiv · doi:10.1101/2025.08.19.25334031 · Cited by 1 · see citing works
Time-related variations in viability of random pattern skin flaps: An experimental study in rats
Aydın, O. E., Cicek, K., Ceylan, E., Tuzcu, A., Pehlevan, A., & Demir, N. (2023) · Chronobiology International · doi:10.1080/07420528.2023.2270706
“Kramer et al. reviewed the chronobiological implications on health and disease (Kramer et al. 2022).”
BackgroundInfluentialCornélissen, G., Otsuka, K., & Hirota, T. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/bk9781839167553-00001
Bedeutung des circadianen Rhythmus für organisch bedingte Erkrankungen
Wiater, A. H. (2024) · Elsevier eBooks · doi:10.1016/b978-3-437-21054-9.00006-9
Ridhani, A. R., Haryadi, R., Hartono, H., Anisah, L., Jarkawi, J., & Handayani, E. S. (2024) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2024.111981
Rational practice of Ayurveda botanicals toward sustainable usage of medicinal plant resources
Acharya, R. (2024) · Journal of Drug Research in Ayurvedic Sciences · doi:10.4103/jdras.jdras_420_24
Ector, C., & Granada, A. E. (2025) · Deutsches Ärzteblatt · doi:10.3238/personko.2025.02.07.03
Upadhyay, A. K., Rowland-Chandler, J., Stewart-Wood, J., Pingarron-Cardenas, G., Tokuda, I., Webb, A., & Locke, J. C. W. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.08.644541
Nahtigal, K., Vasle, A. H., Kreft, T., Skubic, C., Mraz, M., Moškon, M., Dolenc‐Grošelj, L., & Rozman, D. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.22.677736
“…the genetic mechanisms that drive circadian rhythms is crucial, as disruptions in these rhythms are linked to various health conditions [5] , including metabolic disorders (e.g., non-alcoholic fatty liver disease) [6] , cardiovascular diseases (e.g., heart failure) [7] , and sleep…”
Chronotherapy in oncology: New therapeutic horizons through the modulation of circadian rhythms
Griffiths, D., & Innominato, P. F. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-28938-5.00012-x
Pilz, L. K., Kramer, A., Oster, H., & Spies, C. (2025) · AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie · doi:10.1055/a-2351-8543
“…erhöhten Anfälligkeit für eine Reihe von Krankheiten beitragen, u.a. Herz-Kreislauf-und Tumorerkrankungen, metabolisches Syndrom und Depression [4, 5]. erleichtern die langfristige Verfolgung von Ruhe-Aktivi-täts-Rhythmen Ruhe-Aktivi-täts-Rhythmen und Lichtexposition vor und nach einer…”
Self-citationPractical Pharmaceutical Researches Utilizing Clock Genes
Ushijima, K. (2025) · YAKUGAKU ZASSHI · doi:10.1248/yakushi.25-00125
Buekenhout, I., Gomes, A. A., & Leitão, J. (2026) · Sleep Medicine · doi:10.1016/j.sleep.2026.108768
Fusz, K., Deák, A., Závodi, P., Jónás, B., Szilber, V. D., & Kanizsai, P. (2026) · BMJ Open · doi:10.1136/bmjopen-2025-101295
Circadian medicine and biotechnology: engineering the biological clock for health and therapy
Lekshmi, K. M., Sobana, M., Prakash, G. H., Shanmugabharath, V., & Gokulakrishnan, M. (2026) · Biological Rhythm Research · doi:10.1080/09291016.2026.2654520
“…medicine, AI/biotech integration, and circadian enhancement, with their potential impacts and challenges (Zafar et al. 2022; Kramer, 2023; Kramer et al. 2022; Münch and Kramer 2019). impacts, such as artificial light at night, biotechnology mitigates the health consequences of modern…”
Biological rhythms in retinal development
Bagchi, U. (2022) · theses.fr (ABES) · doi:10.70675/f3adc3caz635bz4f0ezbd7az684aff912e21
Circadian Health Training in Latin America: Translating Chronobiology into Clinical Practice
de Andrade, T. G., & Silva, A. C. (2026) · Sleep Science · doi:10.1055/s-0046-1819594
“8 However, the fi eld faces substantial challenges.”
Digital biomarkers in non-communicable diseases
Agha-Mir-Salim, L., Grünewald, E., Balzer, F., & Braune, K. (2026) · Biomarkers · doi:10.1080/1354750x.2026.2682425
“…enabling care teams to tailor the timing of interventions to a person’s biological rhythms. this approach can enhance both short-term and long-term treat-ment outcomes (Kramer et al. 2022). wearable technologies represent a key means of capturing digital biomarkers for circadian rhythms.”
Chronotherapy considerations in lithium treatment for bipolar disorder
Bhatnagar, A., Saha, S., Murray, G., & Ray, S. (2026) · Nature Mental Health · doi:10.1038/s44220-026-00659-9
“The emerging field of circadian medicine seeks to harness the principles of circadian physiology and clock–disease interactions to improve clinical diagnosis, treatment and prevention 18 .”
Sarvandani, M. N., Chen, Q., Karami, M., Garmabi, B., Zare, M., & Rafaiee, R. (2025) · Health and Development Journal · doi:10.34172/jhad.1237
“By synchronizing interventions with a patient’s internal biological clock, healthcare strategies can become more efficient, more responsive, and better adapted to individual physiological needs (17).”
Circadian rhythms in pediatric neurocritical care: interfaces and opportunities
Babinchak, W. M., & Lipton, J. O. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1826615
“Circadian medicine aims to use temporal organization of biomarkers, drug targets, drug metabolism, and the rhythms of health care implementation to optimize diagnosis, care, and outcomes (15).”
Zirkadiane Rhythmen und Chronomedizin
Oster, H. (2026) · Journal für Gynäkologische Endokrinologie/Schweiz · doi:10.1007/s41975-026-00457-7
Self-citationSouabni, M., Sordo, G. C. D., Saurel, M., Peyrel, P., Giacomoni, M., Souabni, M. J., Davenne, D., Gabriel, B. M., St‐Onge, M., & Saidi, O. (2026) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2026.102358
Johnson, E., Smith, R., Brown, L., & Miller, K. (2026) · Journal of Applied Pharmaceutical Technologies and Systems · doi:10.68159/k699635774
Daily Patterns in the Timing of Medication and Supplement Intake
Tran, T., Varshney, S., van Rosmalen, L., Levy, J. L., Laing, K. L., Manoogian, E. N. C., Lam, M. T. Y., & Panda, S. (2026) · Nutrients · doi:10.3390/nu18193291
“These medications are commonly prescribed for chronic conditions that themselves exhibit strong circadian variation—including hypertension, asthma, diabetes, arthritis, gastroesophageal reflux disease, depression, and cardiovascular disease [23–26].”
Goedegebure, M., & Baatout, S. (2026) · Frontiers in Space Technologies · doi:10.3389/frspt.2026.1958668
- Authors
- Kramer, A., Lange, T., Spies, C., Finger, A.-M., Berg, D., & Oster, H.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- University of Lübeck (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Corresponding author
- Kramer, Achim
- Oster, Henrik
- Venue
- PLOS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2022-03-24
- Volume
- 20
- Issue
- 3
- Pages
- e3001567
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC8946668
- OpenAlex
- W4220825346
- Cited by
- 99
- References
- 70
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 25 · 2023: 29 · 2022: 8
- FWCI
- 10.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (278001972 (TRR186/A17), KR 1989/12-1, OS353-10/1, OS353-11/1)
- Horizon 2020 (CLOCK 846016)
- Michael J. Fox Foundation for Parkinson's Research (Foxpark I & II)
- Bundesministerium für Bildung und Forschung (Females Professors Program III)
- Joachim Herz Stiftung (Add-On Fellowship for Interdisciplinary Life Sciences)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- circadian medicine, circadian clock, circadian rhythm, circadian physiology, circadian rhythm disruption, translational research, chronotherapy
- MeSH terms
- Circadian Rhythm, Circadian Clocks
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