4.8 Review

Circadian rhythm as a therapeutic target

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NATURE REVIEWS DRUG DISCOVERY
卷 20, 期 4, 页码 287-307

出版社

NATURE PORTFOLIO
DOI: 10.1038/s41573-020-00109-w

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资金

  1. US National Institute of Health [R01HL154720, R01DK122796, R01DK109574, R01HL133900]
  2. Department of Defense Grant [W81XWH2110032]
  3. American Thoracic Society
  4. American Heart Association [19CDA34660279]
  5. American Lung Association [CA-622265]
  6. Center for Clinical and Translational Sciences pilot project award [1UL1TR003167-01]
  7. Parker B. Francis Fellowship
  8. National Natural Science Foundation of China [81201448, 81972312]
  9. Natural Science Foundation of Hunan Province [2018JJ3736]

向作者/读者索取更多资源

The circadian clock plays a crucial role in integrating external environmental changes and internal physiology, providing temporal precision and robust adaptation to the environment. Disruption of circadian rhythms can lead to adverse health consequences, but there is still an underappreciation of how to take advantage of biological timing for health benefits. Promising progress in research and clinical applications should drive efforts towards a new era of circadian medicine.
The circadian clock evolved in diverse organisms to integrate external environmental changes and internal physiology. The clock endows the host with temporal precision and robust adaptation to the surrounding environment. When circadian rhythms are perturbed or misaligned, as a result of jet lag, shiftwork or other lifestyle factors, adverse health consequences arise, and the risks of diseases such as cancer, cardiovascular diseases or metabolic disorders increase. Although the negative impact of circadian rhythm disruption is now well established, it remains underappreciated how to take advantage of biological timing, or correct it, for health benefits. In this Review, we provide an updated account of the circadian system and highlight several key disease areas with altered circadian signalling. We discuss environmental and lifestyle modifications of circadian rhythm and clock-based therapeutic strategies, including chronotherapy, in which dosing time is deliberately optimized for maximum therapeutic index, and pharmacological agents that target core clock components and proximal regulators. Promising progress in research, disease models and clinical applications should encourage a concerted effort towards a new era of circadian medicine.

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