Summary: Scientists have explained how our internal clocks preserve a roughly 24-hour rhythm even as temperatures change. By applying physics-based mathematical methods to models of gene activity, researchers showed that the rhythm of clock gene expression becomes skewed at higher temperatures—rising faster and decaying more slowly—so that the overall cycle length stays the same.
This change in waveform also alters how the circadian clock responds to environmental day-night cues, helping it remain synchronized with the external light-dark cycle. The insights could shed light on sleep disorders, jet lag, and age-related shifts in circadian timing.
Key facts:
- Waveform distortion: Clock gene expression becomes asymmetric at higher temperatures to conserve period.
- Synchronization stability: Greater distortion makes the clock less sensitive to irregular light-dark signals.
- Biomarker potential: Distortion patterns in clock gene waveforms may help explain individual differences in circadian behavior and disorders.
Source: RIKEN
Researchers led by Gen Kurosawa at the RIKEN Center for Interdisciplinary Theoretical and Mathematical Sciences (iTHEMS) in Japan used theoretical physics to clarify how circadian clocks keep a consistent 24-hour period despite temperature changes.
Their work shows that temperature compensation—the maintenance of a stable circadian period even as chemical processes speed up with heat—can be achieved through subtle distortions in the time course, or waveform, of clock gene expression. In practical terms, the rise in mRNA levels becomes steeper while the decline lengthens, producing an asymmetric cycle that preserves overall timing.
The study was published in PLOS Computational Biology on July 22.
Circadian rhythms govern daily cycles of sleep, hormone release, metabolism, and behavior. These rhythms are driven by molecular feedback loops in which specific genes are periodically activated and then repressed. The resulting oscillations in mRNA and protein levels act like a biological clock that tracks roughly 24 hours.
A long-standing puzzle has been how this clock remains stable when many biochemical reactions accelerate with temperature. To address this, Kurosawa’s team applied tools from theoretical physics—most notably the renormalization group method—to mathematical models of gene-protein dynamics. That method isolates the slow, dominant features that determine the long-term behavior of oscillatory systems.
Their analysis predicted that increasing temperature should make the rising phase of mRNA production faster while extending the falling phase, producing a skewed waveform without changing the cycle length. To test this prediction, the researchers reanalyzed existing experimental data from fruit flies and mice. The empirical data matched the theoretical prediction: higher temperatures were associated with the predicted waveform distortions.
From these results, the team concluded that waveform distortion—principally a lengthening of the decline phase of gene expression—is a central mechanism of temperature compensation in circadian clocks. In other words, the clock preserves period by redistributing time within each cycle rather than by uniformly slowing or speeding all reactions.
The study also explored how waveform changes affect synchronization with external cues. The models show that as waveform distortion increases, the circadian oscillator becomes less responsive to fluctuating light-dark inputs, narrowing the range over which external cues can shift the clock. This theoretical outcome is consistent with observations in flies and fungi, and it has practical relevance because many people experience irregular light exposure in modern life.
Kurosawa emphasizes that identifying the precise molecular processes that slow the decline of mRNA during each cycle is an important next step. Those mechanisms could include temperature-dependent changes in transcriptional repression, mRNA stability, or protein feedback loops.
Researchers also plan to investigate variation in waveform distortion across species and among individuals. Factors such as age, genetic background, and lifestyle may affect the degree of distortion, potentially making it a useful biomarker for circadian health. In the long term, quantifying waveform features could improve understanding of sleep disorders, inform strategies to reduce jet lag, and clarify how aging alters internal timing.
About this circadian rhythm research news
Author: Masataka Sasabe
Source: RIKEN
Contact: Masataka Sasabe – RIKEN
Image: The image is credited to Neuroscience News
Original research: Open access.
Waveform distortion for temperature compensation and synchronization in circadian rhythms: An approach based on the renormalization group method by Gen Kurosawa et al., PLOS Computational Biology
Abstract
Waveform distortion for temperature compensation and synchronization in circadian rhythms: An approach based on the renormalization group method
Many biochemical processes accelerate with higher temperature, yet circadian periods remain remarkably stable—a phenomenon called temperature compensation—while clocks still synchronize to the 24-hour light-dark cycle.
This work theoretically investigates how distortions in the waveform of circadian gene-protein oscillations contribute to temperature compensation and synchronization. Analysis of the Goodwin model and related oscillators shows that increasing temperature should lengthen the decreasing phase of protein oscillations, producing asymmetric waveforms that preserve period.
The waveform–period relationship appears in diverse oscillator models, including Lotka–Volterra and van der Pol systems, and in more detailed mammalian circadian models. Reanalysis of existing experimental datasets supports the predicted waveform distortions and their effect on synchronization range.
These results suggest that waveform shape is fundamental to how biological clocks maintain stable timing across temperatures and remain entrained to environmental cycles.