The biological clock maintains a 24-hour cycle by changing the functioning of genes in warm conditions

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 stable 24-hour cycle even when the temperature changes.

They found that this stability is achieved by 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 accurate time, but also affects how well our internal clocks sync with the day-night cycle. The study is published in the journal PLOS Computational Biology.

Have you ever wondered how your body knows when to sleep or wake up? The answer is simple: Your body has a biological clock that runs on a roughly 24-hour cycle. But because most chemical reactions speed up as temperatures rise, it’s been a mystery how the body compensates for temperature changes throughout the year — or even as we move between the summer heat outside and the cool of air-conditioned rooms.

The biological clock works by cyclical fluctuations in levels of mRNA—the molecules that code for protein production—that occur when certain genes are rhythmically turned on and off. Just as the motion of a pendulum can be described by a mathematical sine wave, rising and falling smoothly, the rhythm of mRNA production and decay can be represented by an oscillatory wave.

Kurosawa’s team at RIKEN iTHEMS, together with colleagues at YITP Kyoto University, applied methods from theoretical physics to analyze the mathematical models that describe these rhythmic oscillations of mRNA. In particular, they used the renormalization group method, a powerful tool from physics that allows one to extract key, slowly changing dynamic processes from the mRNA rhythm system.

The analysis showed that as the temperature increased, mRNA levels rose faster and fell more slowly, but the duration of one cycle remained constant. On a graph, this rhythm at high temperatures looked like a distorted, asymmetric wave.

To test the theoretical conclusions in living organisms, the researchers analyzed experimental data on fruit flies and mice. Indeed, at elevated temperatures, these animals showed the predicted waveform distortions, which confirmed the correctness of the theoretical model.

The scientists conclude that waveform distortion is key to temperature compensation in the biological clock, specifically to slowing the decline of mRNA levels with each cycle.

The team also found that waveform distortion affects the body clock's ability to synchronize with external cues, such as light and darkness. The analysis showed that with greater waveform distortion, the clock is more stable and less affected by external cues.

This theoretical conclusion coincided with experimental observations in flies and fungi and is important because irregular light-dark cycles have become part of modern life for most people.

"Our results show that waveform distortion is a critical element in how the biological clock remains accurate and synchronized, even as temperature changes," Kurosawa says.

He adds that future research could focus on identifying the molecular mechanisms that slow the decline in mRNA levels and cause the waveform distortion. The researchers also hope to study how this distortion varies between species or even individuals, since age and individual differences can affect the functioning of the biological clock.

“In the long term,” Kurosawa notes, “the degree of waveform distortion in clock genes could become a biomarker for better understanding sleep disorders, jet lag, and the effects of aging on the internal clock. It could also reveal universal patterns of rhythms — not just in biology but in any system with repeating cycles.”