Study reveals how the body clock stays on track despite temperature changes

Researchers led by Gen Kurosawa at the RIKEN Center for Interdisciplinary Theoretical and Mathematical Sciences (iTHEMS) in Japan have used theoretical physics to discover how our biological clock maintains a consistent 24-hour cycle-even as temperatures change. They found that this stability is achieved through a subtle shift in the "shape" of gene activity rhythms at higher temperatures, a process known as waveform distortion. This process not only helps keep time steady but also influences how well our internal clock synchronizes with the day-night cycle. The study was published in PLOS Computational Biology on July 22.

Have you ever wondered how your body knows when it's time to sleep or wake up? The simple answer is that your body has a biological clock, which runs on a roughly 24-hour cycle. But because most chemical reactions speed up as temperatures rise, how our bodies compensate for changing temperatures throughout the year-or even as we move back and forth between the outdoor summer heat and indoor air-conditioned rooms-has remained largely a mystery.

Our biological clock is powered by cyclical patterns of mRNA-the molecules that code for protein production-which result from certain genes being rhythmically turned on and off. Just as the back and forth of a swinging pendulum over time can be described mathematically as a sine wave, smoothly going up and coming down over and over, so can the rhythm of mRNA production and decline.

Kurosawa's research team at RIKEN iTHEMS and a collaborator at YITP, Kyoto University, drew on theoretical physics to analyze the mathematical models that describe this rhythmic rise and fall of mRNA levels. Specifically, they used the renormalization group method, a powerful approach adapted from physics, to extract critical slow-changing dynamics from the system of mRNA rhythms. Their analysis revealed that at higher temperatures mRNA levels should rise more quickly and decline more slowly, but importantly, the duration of one cycle should stay constant. When graphed, this high-temperature rhythm looks like a skewed, asymmetrical waveform.

But does this theorized change actually happen? To test this theory in real organisms, the researchers examined experimental data from fruit flies and mice. Sure enough, at higher temperatures, these animals showed the predicted waveform distortions, confirming that the theoretical predictions align with biological reality. The researchers conclude that waveform distortion is the key to temperature compensation in the biological clock, specifically the slowing down of mRNA-level decline during each cycle.

The team also found that waveform distortion affects how well the biological clock synchronizes with environmental cues, such as light and darkness. The analysis predicted that when the waveform becomes more distorted, the biological clock is more stable, and environmental cues have little effect on it. This theoretical prediction matches experimental observations in flies and fungi and is significant because irregular light-dark cycles are part of modern-day life for most people.

Our findings show that waveform distortion is a crucial part of how biological clocks remain accurate and synchronized, even when temperatures change."

Gen Kurosawa, RIKEN Center for Interdisciplinary Theoretical and Mathematical Sciences

He adds that future research can now focus on identifying the exact molecular mechanisms that slow down the decline in mRNA levels, which leads to the waveform distortion. Scientists also hope to explore how this distortion varies across species-or even between individuals-since age and personal differences may influence how our internal clocks behave.

"In the long term," Kurosawa notes, "the degree of waveform distortion in clock genes could be a biomarker that helps us better understand sleep disorders, jet lag, and the effects of aging on our internal clocks. It might also reveal universal patterns in how rhythms work-not just in biology, but in many systems that involve repeating cycles."