Why Do Humans Are More Active During the Day Than at Night? Solving the Mystery of Our Daily Rhythm: The "Robust Cellular Clock" That Supports Human Diurnality

Why Do Humans Are More Active During the Day Than at Night? Solving the Mystery of Our Daily Rhythm: The "Robust Cellular Clock" That Supports Human Diurnality

Many of us share the feeling that staying up late can easily lead to poor health, while being active in the morning sunlight helps us feel balanced. But why are humans diurnal, waking during the day and sleeping at night? Tracing back through evolutionary history, early mammals are believed to have been active mainly at night to avoid the dinosaurs that roamed during the day. Despite this, some lineages, including humans, have independently transitioned back to being diurnal multiple times. A study strongly suggesting that the answer lies not in the "brain" but in the "cells" has been reported.


The difference between diurnal and nocturnal couldn't be fully explained by brain wiring

At the center of the circadian rhythm is the "master clock" in the brain. However, the fundamental operation of this master clock does not significantly differ between nocturnal and diurnal animals. This has made the question of "how the transition to diurnality occurred" a challenging one. The recent study suggests that the decisive difference lies not in the brain circuits but in how "individual cells," including those in the periphery, respond to fluctuating internal environmental signals throughout the day.


Small fluctuations within the body drive the cellular clock

Within our bodies, there are slight fluctuations in temperature, fluid balance (osmotic pressure), and nutritional status over a 24-hour period. The research team considered that these physical and chemical "minute diurnal variations" influence chemical reactions and protein synthesis/modification within cells, providing clues for cells to interpret whether it is "day or night."


What's interesting here is that even when given the same "temperature diurnal cycle," cells from diurnal animals and those from nocturnal animals can shift their circadian clocks (phase shifts) in opposite directions. In other words, the "meaning" that cells derive from the same external stimulus differs between diurnal and nocturnal types.


The key players are mTOR and WNK—The "metabolic command center" links to time-of-day preference

The study highlights two signaling pathways as central to creating differences. One is mTOR (mechanistic target of rapamycin), the cell's "metabolic command center" that oversees protein synthesis and other processes according to nutritional and energy states. The other is WNK (with-no-lysine), known as a network involved in adjusting ion and osmotic balance. It was observed that human and mouse cells change protein synthesis and enzyme activity "differently/sometimes in opposite directions" in response to temperature changes, suggesting differences in the sensitivity of mTOR and WNK are behind this.


The point here is that focusing solely on the "circadian clock" can lead to oversights. The gears of the clock themselves are not different between diurnal and nocturnal types; rather, the way the "metabolic and fluid sensor systems" input to the gears reacts differently. As a result, even with the same diurnal variations, individuals that find it advantageous to be active during the day and those that find it advantageous to be active at night emerge.


Diurnal cells are "resistant to temperature fluctuations"—a robust cellular clock

Furthermore, a key point of the paper is that diurnal cells are reported to be "less affected (robust)" in terms of protein synthesis, phosphorylation, and circadian clock timing in response to temperature changes. In other words, the diurnal cellular clock may be designed to be less susceptible to fluctuations in temperature and osmotic pressure.


This "robustness" makes sense in the transition to diurnality. During the day, external temperatures and activity levels are more prone to fluctuation, and eating, exercise, and stress responses are more likely to occur. If one is to be active during such a noisy time, a mechanism that prevents the basic functions of cells from being swayed by fluctuations becomes advantageous.


Traces of genetic evolution: mTOR and related networks "evolved rapidly"

The research team also conducted comparative genomic analysis and reported that in diurnal mammals, gene groups within networks such as mTOR and WNK show "faster evolution than usual." This suggests that the transition to diurnality required not just a change in behavioral preference but a "genetic-level tuning" of the basic physiology of cells.


And the decisive factor: Suppressing mTOR in nocturnal mice shifts them towards "diurnality"

Even this is stimulating enough, but there is an even more in-depth experiment. When mTOR activity was suppressed in nocturnal mice, their cells, tissues, and behavior shifted towards diurnality. The article introduces that a diet-based intervention lowered mTOR function, resulting in activity times shifting towards the day.


Of course, it is dangerous to simplistically conclude that "mice were completely converted to diurnality." Behavior involves multiple factors such as light, predators, sociality, and energy efficiency. Nevertheless, the significance of demonstrating through experiments that tuning metabolic signals within cells can influence an animal's "preference for activity time" is substantial.


Implications for medicine: Supporting "circadian medicine" that leverages time

One reason this research is garnering attention is its connection to medicine. The effectiveness and side effects of drugs can vary depending on the time of day, and circadian medicine, which optimizes the "when" of treatment, is gaining attention. mTOR is an important target in drug discovery, cancer research, and metabolic research, and it could serve as a bridge connecting chronobiology and clinical practice. MRC's explanation also explicitly suggests implications for areas where treatment timing affects efficacy.


On the other hand, there are also points of caution. mTOR is multifunctional, and it's not simply a matter of "suppressing it for health." The impact of interventions on other physiological functions and their long-term safety are separate issues. The value of the research lies not in proposing easy health methods but in concretizing the mechanism by which "basic cellular pathways are linked to time-of-day behavior."


An unexpected connection to climate change: "Shifts in activity time" could shake ecosystems

The article and UKRI's announcement also raise climate change as another implication. If temperatures change, the diurnal signals received by cells could also alter. Moreover, if the correspondence between food (prey) availability and the external environment collapses, mammals might shift their activity times. If many species shift their activity times, the relationships of predation, pollination, competition, etc., could change in a chain reaction, impacting the balance of ecosystems—such concerns are being raised.


Reactions on social media: In expert communities, it's a "textbook case" and "effective for circadian medicine"

So how was this story received on social media? Rather than going viral on a large scale, it seems that reactions are first emerging within the researcher and adjacent field communities.


For example, one of the authors introduced the research on LinkedIn, conveying the idea that "the difference between day and night is engraved at the cellular level" and cautioning about extrapolating research across species. They also touched on the ambition to use microfluidic technology, which can precisely control the cellular environment over time, to bring realistic diurnal variations into experimental systems.


In the comments section, there are voices such as: ① "It's important because the discussion about timing affecting drug efficacy is heating up," ② "It really seems like it could be in textbooks," and ③ "Could it lead to interventions for insomnia and wakefulness?" All of these indicate a focus not just on trivia but on circadian medicine, translational research (the difficulty of transferring insights from animals to humans), and intervention possibilities.


Can "night owls" change?—Key takeaways for readers

Many people reading this article might first wonder, "So can a night owl's nature be changed with mTOR?" However, research does not immediately provide "lifestyle techniques." The claim here is rather an update to the worldview that the factors determining diurnal and nocturnal tendencies are deeply rooted not only in light stimuli and the brain's clock but also in the design of cells' metabolic and fluid sensors.


In other words, human rhythms are not something that can be managed by "willpower" alone or discussed solely in terms of "sleep duration." Body temperature, nutrition, osmotic pressure, protein synthesis—these "subtle yet fundamental cellular activities" ultimately outline the behavior of "when to be active." Evolutionary choices have accumulated there, making us creatures of the day.


And now, we have entered an era of rapidly changing environments. If temperature and the seasonality of food change, the assumptions of diurnal readings by cells may also waver. Understanding the mechanism of the day-night switch can provide clues not only for human health but also for the future of ecosystems. The fact that the "normalcy of waking up during the day" actually relies on a very precise and environmentally sensitive mechanism might be the most significant takeaway from this study.


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