Time of day as a critical variable in biology

Abstract

Background: Circadian rhythms are important for all aspects of biology; virtually every aspect of biological function varies according to time of day. Although this is well known, variation across the day is also often ignored in the design and reporting of research. For this review, we analyzed the top 50 cited papers across 10 major domains of the biological sciences in the calendar year 2015. We repeated this analysis for the year 2019, hypothesizing that the awarding of a Nobel Prize in 2017 for achievements in the field of circadian biology would highlight the importance of circadian rhythms for scientists across many disciplines, and improve time-of-day reporting.

Results: Our analyses of these 1000 empirical papers, however, revealed that most failed to include sufficient temporal details when describing experimental methods and that few systematic differences in time-of-day reporting existed between 2015 and 2019. Overall, only 6.1% of reports included time-of-day information about experimental measures and manipulations sufficient to permit replication.

Conclusions: Circadian rhythms are a defining feature of biological systems, and knowing when in the circadian day these systems are evaluated is fundamentally important information. Failing to account for time of day hampers reproducibility across laboratories, complicates interpretation of results, and reduces the value of data based predominantly on nocturnal animals when extrapolating to diurnal humans.

Keywords: Behavioral sciences; Cardiac and cardiovascular systems; Circadian rhythms; Endocrinology and metabolism; Immunology; Neuroscience; Oncology; Pharmacology; Physiology; Time of day.

Fig. 1

Stack plot indicating the incidence of reporting of (A) the time-of-day at which key experimental procedures were performed, and (B) experimental lighting cycles among the 50 highest-cited biology reports from 2015 and from 2019. See Methods (Measures and criteria) for time-of-day reporting criteria

Fig. 2

Reporting in immunology. A Time-of-day and B light cycle reporting

Fig. 3

Reporting in neuroscience. A Time-of-day and B light cycle reporting

Fig. 4

Reporting in physiology. A Time-of-day and B light cycle reporting

Fig. 5

Reporting in pharmacology and pharmacy. A Time-of-day and B light cycle reporting

Fig. 6

Reporting in reproductive biology. A Time-of-day and B light cycle reporting

Fig. 7

Reporting in endocrinology and metabolism. A Time-of-day and B light cycle reporting

Fig. 8

Reporting in behavioral sciences. A Time-of-day and B light cycle reporting

Fig. 9

Reporting in oncology. A Time-of-day and B light cycle reporting

Fig. 10

Reporting in cardiac and cardiovascular systems. A Time-of-day and B light cycle reporting

Fig. 11

Time-of-day and light cycle reporting across 10 domains of biological sciences. A, B Time-of-day and C, D light cycle reporting in the top 50 papers across all 10 domains in 2015 and 2019. Each donut chart represents a total of 500 articles