ObjectivesIn this study, we investigated daily fluctuations in molecular (gene expression) and physiological (biomechanical muscle properties) features in human peripheral cells and their correlation with exercise performance.Methods21 healthy participants (13 men and 8 women) took part in three test series: for the molecular analysis, 15 participants provided hair, blood or saliva time-course sampling for the rhythmicity analysis of core-clock gene expression via RT-PCR. For the exercise tests, 16 participants conducted strength and endurance exercises at different times of the day (9h, 12h, 15h and 18h). Myotonometry was carried out using a digital palpation device (MyotonPRO), five muscles were measured in 11 participants. A computational analysis was performed to relate core-clock gene expression, resting muscle tone and exercise performance.ResultsCore-clock genes show daily fluctuations in expression in all biological samples tested for all participants. Exercise performance peaks in the late afternoon (15–18 hours for both men and women) and shows variations in performance, depending on the type of exercise (eg, strength vs endurance). Muscle tone varies across the day and higher muscle tone correlates with better performance. Molecular daily profiles correlate with daily variation in exercise performance.ConclusionTraining programmes can profit from these findings to increase efficiency and fine-tune timing of training sessions based on the individual molecular data. Our results can benefit both professional athletes, where a fraction of seconds may allow for a gold medal, and rehabilitation in clinical settings to increase therapy efficacy and reduce recovery times.

A bidirectional interaction between the circadian network and effector mechanisms of immunity brings on a proper working of both systems. In the present study, we used Hodgkin lymphoma (HL) as an experimental model for a type of cancer involving cells of the immune system. We identified this cancer type among haematological malignancies has having a strong differential expression of core-clock elements. Taking advantage of bioinformatics analyses and experimental procedures carried out in III- and IV-stage HL cells, and lymphoblastoid B cells, we explored this interplay and bear out diverse interacting partners of both systems. In particular, we assembled a wide-ranging network of clock-immune-related genes and pinpointed TNF as a crucial intermediary player. A robust circadian clock hallmarked III-stage lymphoma cells, differently from IV-stage HL cells, which do not harbour a properly functioning clockwork. TNF and circadian gene modulation impacted on clock genes expression and triggered phenotypic changes in lymphoma cells, suggesting a crucial involvement of core-clock elements and TNF in the physiopathological mechanisms hastening malignancy. Our results move forward our understanding of the putative role of the core-clock and TNF in the pathobiology of Hodgkin lymphoma, and highlight their influence in cellular proliferation and migration in lymphatic cancers.

Tailoring medical interventions to a particular patient and pathology has been termed personalized medicine. The outcome of cancer treatments is improved when the intervention is timed in accordance with the patient's internal time. Yet, one challenge of personalized medicine is how to consider the biological time of the patient. Prerequisite for this so-called chronotherapy is an accurate characterization of the internal circadian time of the patient. As an alternative to time-consuming measurements in a sleep-laboratory, recent studies in chronobiology predict circadian time by applying machine learning approaches and mathematical modelling to easier accessible observables such as gene expression. Embedding these results into the mathematical dynamics between clock and cancer in mammals, we review the precision of predictions and the potential usage with respect to cancer treatment and discuss whether the patient’s internal time and circadian observables, may provide an additional indication for individualized treatment timing. Besides the health improvement, timing treatment may imply financial advantages, by ameliorating side effects of treatments, thus reducing costs. Summarizing the advances of recent years, this review brings together the current clinical standard for measuring biological time, the general assessment of circadian rhythmicity, the usage of rhythmic variables to predict biological time and models of circadian rhythmicity.