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.

Circadian rhythms in the gut microbiota shape sex differences in host gene expression and metabolism

“…Lastly, our studies may provide some practical considerations for the study of sex differences in preclinical and clinical settings. Homeostatic and biological functions vary across time of day, and our results show that when these processes are assessed may affect whether sex differences are detected (Nelson et al, 2021, 2022). Our reconstruction of some, but certainly not all, sex differences in the onset, acrophase, and amplitude of circadian rhythms in host-microbe interactions may provide guidance in selecting the right time of day to collect data.…”

Time of Sample Collection Critical for Microbiome Replicability

“…Only 0.32% reported a specific time of sample collection ( Fig S1A-C ). A recent study of biological sciences articles confirmed a low percentage of time-of-day information reporting in a broader field 26 . Since microbiome studies do not commonly report time of sample collection in their methods, we investigated the effects of microbiome sample collection on the potential interpretation of a study using the datasets from our meta-analysis.…”

Non-alcoholic steatohepatitis disrupts diurnal liver transcriptome rhythms in mice

“…Although time is an important regulatory element for health (3), the control for or evaluation of (day-) time as a variable factor is often neglected in many research fields (6). We hypothesized that a lack of control for sampling time augment inconsistencies in results between different NASH studies that used a similar NASH-inducing model.…”

“…Although the importance of circadian rhythms in liver physiology is well known, many basic and clinical studies often pay little attention to this factor when taking and analysing samples. A recent study evaluated the top-50 cited papers in 10 different fields between 2015 and 2019 showing that only 6.1% of the studies included time-of-day information (6). In recent years, the advances in omics techniques and analysis have clearly demonstrated that a substantial portion of the transcriptome, proteome, and metabolome shows rhythmic patterns (7–11).…”