CIRCADIAN RHYTHMS IN 2018

The arrival of circadian medicine

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Circadian rhythm research is beginning to show how rhythms sustain health. Genome-wide transcriptome, metabolome and proteome studies have improved our understanding of circadian regulation. This knowledge is leveraged for behavioural interventions that optimize daily rhythms, the timing of drug delivery and the targeting of clock components to prevent or treat chronic diseases.

Key advances

  • A reference human circadian transcriptome atlas elucidated tissue-specific circadian regulation1.

  • The human plasma proteome shows diurnal changes and shift work affects a subset of these temporal changes4,5.

  • A high-fat diet disrupts the temporal coordination of transcripts and metabolites across multiple organs in rodents6.

  • Time-restricted eating among men at risk of prediabetes improves blood glucose control and reduces blood pressure without causing weight loss7.

  • Timed administration of drugs without changing dosage can improve potency of anti-inflammatory drugs and pharmacological targeting of circadian clock is a new approach to treat cancer9,10.

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References

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    Ruben, M. D. et al. A database of tissue-specific rhythmically expressed human genes has potential applications in circadian medicine. Sci. Transl Med. 10, eaat8806 (2018).

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    Qian, J. & Scheer, F. A. Circadian system and glucose metabolism: implications for physiology and disease. Trends Endocrinol. Metab. 27, 282–293 (2016).

  3. 3.

    Mure, L. S. et al. Diurnal transcriptome atlas of a primate across major neural and peripheral tissues. Science 359, eaao0318 (2018).

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    Depner, C. M. et al. Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome. Proc. Natl Acad. Sci. USA 115, E5390–E5399 (2018).

  5. 5.

    Wefers, J. et al. Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle. Proc. Natl Acad. Sci. USA 115, 7789–7794 (2018).

  6. 6.

    Dyar, K. A. et al. Atlas of circadian metabolism reveals system-wide coordination and communication between clocks. Cell 174, 1571–1585 (2018).

  7. 7.

    Sutton, E. F. et al. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab. 27, 1212–1221 (2018).

  8. 8.

    Hatori, M. et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 15, 848–860 (2012).

  9. 9.

    Winter, C. et al. Chrono-pharmacological targeting of the CCL2-CCR2 axis ameliorates atherosclerosis. Cell Metab. 28, 175–182 (2018).

  10. 10.

    Sulli, G. et al. Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence. Nature 553, 351–355 (2018).

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Author information

Correspondence to Satchidananda Panda.

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Competing interests

S.P. has written a book “The Circadan Code” for which he is paid royalty.

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Panda, S. The arrival of circadian medicine. Nat Rev Endocrinol 15, 67–69 (2019) doi:10.1038/s41574-018-0142-x

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