1 Introduction

Circadian rhythms are intrinsic, approximately 24-hour cycles that regulate various physiological and behavioral processes in almost all living organisms, from bacteria to humans. These rhythms are driven by an internal time-keeping system known as the circadian clock, which synchronizes biological functions with the external environment, primarily the light-dark cycle (Sanchez et al., 2021; Zheng et al., 2021; Yang et al., 2023). The circadian clock is crucial for maintaining homeostasis, influencing sleep-wake cycles, feeding behaviors, hormone release, and other vital functions (King and Takahashi, 2000; Bloch et al., 2013). Disruptions in circadian rhythms can lead to adverse health effects, including metabolic disorders, impaired cognitive function, and increased susceptibility to chronic diseases (Goede et al., 2018; Meli, 2018).

The study of circadian rhythms has a rich history, dating back to the early observations of daily leaf movements in plants by Jean-Jacques d'Ortous de Mairan in the 18th century. However, significant advancements were made in the 20th century with the discovery of the suprachiasmatic nucleus (SCN) in the hypothalamus as the master circadian clock in mammals (King and Takahashi, 2000; Sanchez et al., 2021). The identification of core clock genes such as Clock, Bmal1, Period, and Timeless in drosophila and mammals marked a new era in circadian biology, providing a molecular framework for understanding circadian mechanisms (King and Takahashi, 2000; Panda, 2016). The awarding of the Nobel Prize in Physiology or Medicine in 2017 to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for their work on the molecular mechanisms of circadian rhythms underscored the importance of this field (Meli, 2018).

This study provides a comprehensive overview of the mechanisms and functions of circadian rhythms in animals. This study explores the molecular and genetic underpinnings of circadian clocks, their role in regulating physiological processes, and the impact of environmental factors on circadian regulation; additionally, discusses the adaptive significance of circadian rhythms in various animal species and the consequences of circadian disruption on health and fitness. By synthesizing current research findings, this study seeks to highlight the complexity and importance of circadian rhythms, offering insights into potential areas for future investigation.

2 Molecular Mechanisms of Circadian Rhythms

2.1 Core components of the molecular clock

The molecular clock in animals is primarily driven by a set of core clock genes that form a transcription-translation feedback loop (TTFL). In mammals, the basic helix-loop-helix (bHLH) PAS (PER-ARNT-SIM) transcription factors CLOCK and BMAL1 are central to this mechanism. These proteins form a heterodimer that activates the transcription of Period (Per) and Cryptochrome (Cry) genes. The protein products of these genes then inhibit the activity of the CLOCK:BMAL1 complex, thereby closing the feedback loop and generating rhythmic oscillations with a period of approximately 24 hours (King and Takahashi, 2000; Lowrey and Takahashi, 2000; Partch et al., 2014; Takahashi, 2015).

In addition to the core loop, there are auxiliary loops that help stabilize and fine-tune the circadian rhythms. For instance, the nuclear receptors REV-ERBα and RORα form a secondary feedback loop that regulates the expression of Bmal1, adding another layer of control to the circadian system (Isojima et al., 2003; Schmutz et al., 2010). This intricate network of feedback loops ensures the robustness and precision of the circadian clock.

2.2 Genetic regulation of circadian rhythms

The genetic regulation of circadian rhythms involves not only the core clock genes but also a multitude of other genes that interact with the core components. For example, the light-dark cycle, a primary environmental cue, influences the expression of clock genes through photic entrainment pathways. In mammals, light signals received by the retina are transmitted to the suprachiasmatic nucleus (SCN) in the hypothalamus, which acts as the master circadian pacemaker. This signal ultimately leads to the resetting of the core clock mechanism in the SCN by modulating the expression of Per and Cry genes (Lowrey and Takahashi, 2000; Meyer-Bernstein and Sehgal, 2001).

Moreover, post-translational modifications such as phosphorylation, nuclear entry, and degradation of clock proteins are crucial for the proper functioning of the circadian clock. These modifications ensure that the feedback loops operate with the necessary precision and stability. For instance, the phosphorylation of PER proteins by casein kinase 1 (CK1) regulates their stability and nuclear translocation, which is essential for the timely repression of CLOCK:BMAL1 activity (Isojima et al., 2003).

2.3 Feedback loops and their role in maintaining circadian rhythms

Feedback loops are fundamental to the maintenance of circadian rhythms. The primary TTFL involves the activation of Per and Cry genes by the CLOCK:BMAL1 complex, followed by the inhibition of this complex by the PER and CRY proteins. This loop generates the basic oscillatory pattern of the circadian clock (King and Takahashi, 2000; Lowrey and Takahashi, 2000; Takahashi, 2015).

In addition to the primary loop, secondary feedback loops involving nuclear receptors such as REV-ERBα and RORα play a critical role in stabilizing the circadian rhythms. These receptors regulate the expression of Bmal1, thereby influencing the activity of the CLOCK:BMAL1 complex. The interaction between these loops ensures that the circadian clock can adapt to changes in environmental conditions while maintaining its intrinsic rhythmicity (Figure 1) (Isojima et al., 2003; Schmutz et al., 2010).

Furthermore, recent studies have highlighted the importance of non-transcriptional mechanisms in circadian timekeeping. For example, the oxidation of peroxiredoxin proteins has been identified as a transcription-independent rhythmic biomarker, suggesting that post-translational mechanisms also contribute significantly to the maintenance of circadian rhythms (O’Neill et al., 2010). This indicates that the oldest oscillator components may be non-transcriptional in nature and conserved across different kingdoms of life.

The molecular mechanisms of circadian rhythms in animals involve a complex interplay of transcriptional and post-transcriptional processes. The core components of the molecular clock, genetic regulation, and multiple feedback loops work together to generate and maintain the precise 24-hour cycles that are essential for the temporal organization of biological functions.

3 Physiological Mechanisms of Circadian Rhythms

3.1 Neural pathways involved in circadian regulation

The central pacemaker of the mammalian circadian timing system is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. This master clock coordinates the timing of oscillators throughout the brain and body, ensuring synchronization with the external environment, primarily through light-dark (LD) cycles (Mohawk et al., 2012; Eckel-Mahan and Sassone-Corsi, 2013; Panda, 2016). The SCN receives photic information from the retina via the retinohypothalamic tract, which transmits signals through neurotransmitters such as glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP) (Eckel-Mahan and Sassone-Corsi, 2013). These signals activate intracellular pathways in SCN neurons, leading to changes in clock gene expression and neuronal activity (Eckel-Mahan and Sassone-Corsi, 2013; Pitsillou et al., 2020). Additionally, the SCN communicates with peripheral clocks through both neuronal and humoral pathways, ensuring that physiological processes are synchronized across the entire organism (Panda, 2016; Pitsillou et al., 2020; Guan and Lazar, 2021). The SCN's ability to integrate external light information and adapt cellular clocks in all tissues is crucial for maintaining circadian rhythms (Pitsillou et al., 2020).

3.2 Hormonal control of circadian rhythms

Hormones play a significant role in the regulation of circadian rhythms, acting as mediators between the central clock and peripheral tissues. The SCN influences the release of various hormones, including melatonin, cortisol, and insulin, which help synchronize peripheral clocks with the central pacemaker (Panda, 2016; Pitsillou et al., 2020; Guan and Lazar, 2021). Melatonin, produced by the pineal gland, is a well-known marker of circadian rhythms and is regulated by the SCN through sympathetic nervous system pathways (Panda, 2016). Cortisol, a glucocorticoid hormone, follows a circadian pattern with peak levels in the early morning, driven by the SCN's influence on the hypothalamic-pituitary-adrenal (HPA) axis (Panda, 2016; Pitsillou et al., 2020). Insulin secretion is also under circadian control, with the SCN modulating pancreatic function to align glucose metabolism with feeding cycles. These hormonal signals ensure that physiological processes such as sleep-wake cycles, metabolism, and immune function are appropriately timed with the external environment (Eckel-Mahan and Sassone-Corsi, 2013; Pitsillou et al., 2020; Guan and Lazar, 2021).

3.3 Interaction between circadian rhythms and metabolic processes

Circadian rhythms are intricately linked with metabolic processes, with the central clock in the SCN coordinating metabolic functions across various tissues. The SCN regulates feeding-fasting cycles, energy expenditure, and glucose homeostasis through its influence on peripheral clocks in organs such as the liver, pancreas, and adipose tissue (Mohawk et al., 2012; Tsang et al., 2013; Guan and Lazar, 2021). Clock genes, such as Period (PER) and Cryptochrome (CRY), play a crucial role in this regulation by modulating the expression of genes involved in metabolic pathways. For instance, the clock component PER2 interacts with nuclear receptors like PPARalpha and REV-ERBalpha, coordinating the expression of genes involved in glucose metabolism and lipid homeostasis (Asher and Schibler, 2011). Disruptions in circadian rhythms can lead to metabolic disorders, highlighting the importance of maintaining synchrony between the central clock and peripheral metabolic processes (Asher and Schibler, 2011; Robles et al., 2017). Recent studies have also shown that redox reactions and transcriptional loops are interconnected, further linking circadian rhythms with metabolic regulation (Figure 2) (Robles et al., 2017). Understanding these interactions is essential for developing therapeutic strategies to address metabolic diseases associated with circadian disruption (Asher and Schibler, 2011; Robles et al., 2017).

The physiological mechanisms of circadian rhythms involve complex interactions between neural pathways, hormonal signals, and metabolic processes. The SCN serves as the central pacemaker, integrating external light information and coordinating peripheral clocks through neuronal and humoral pathways. Hormones such as melatonin, cortisol, and insulin play crucial roles in synchronizing physiological processes with the central clock. Additionally, circadian rhythms are tightly linked with metabolic functions, with clock genes modulating the expression of genes involved in metabolism. Disruptions in these mechanisms can lead to various health issues, emphasizing the importance of maintaining circadian synchrony.

4 Behavioral Functions of Circadian Rhythms

4.1 Sleep-wake cycles and their significance

Circadian rhythms play a crucial role in regulating the sleep-wake cycles of animals. These approximately 24-hour cycles are driven by a master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which coordinates various physiological and behavioral processes, including sleep timing (Sanchez et al., 2021). The integrity of the sleep-wake cycle is essential for maintaining health and homeostasis. Disruptions in these rhythms can lead to various health issues, including metabolic disorders and impaired immune function (Figure 3) (Kennaway, 2005; Sanchez et al., 2021).

The sleep-wake cycle is influenced by rhythmic hormones such as melatonin and cortisol, which are regulated by the circadian clock. Melatonin, often referred to as the "sleep hormone," is secreted in response to darkness and promotes sleep, while cortisol levels peak in the early morning to promote wakefulness (Koop and Oster, 2021). The synchronization of sleep-wake cycles with the external light-dark cycle ensures that animals are active during optimal times for feeding and other activities, thereby enhancing survival and reproductive success (Singh and Kumar, 2018; Koop and Oster, 2021).

4.2 Feeding and foraging behaviors influenced by circadian rhythms

Feeding and foraging behaviors in animals are also under circadian control. The circadian clock regulates the release of hormones such as leptin, ghrelin, insulin, and orexin, which influence hunger and satiety (Koop and Oster, 2021). These hormonal rhythms ensure that feeding occurs at times when food is most likely to be available and when the body is best prepared to metabolize nutrients (Panda, 2016).

In Drosophila, for example, the circadian clock in the brain's pars intercerebralis (PI) region regulates feeding rhythms. Neurons expressing the neuropeptide SIFamide (SIFa) are crucial for maintaining these rhythms, while neurons expressing Drosophila insulin-like peptides (DILPs) influence overall food consumption but not the rhythmicity of feeding (Dreyer et al., 2019). This distinction highlights the complex interplay between circadian and homeostatic mechanisms in regulating feeding behavior.

Moreover, time-restricted feeding, which aligns feeding times with the natural circadian rhythm, has been shown to sustain robust diurnal rhythms and alleviate metabolic diseases in experimental animal models (Panda, 2016). This suggests that maintaining proper circadian timing of feeding can have significant health benefits.

4.3 Reproductive behaviors and circadian regulation

Reproductive behaviors in animals are intricately linked to circadian rhythms. The timing of reproductive events, such as mating, ovulation, and parental care, is often synchronized with the light-dark cycle to optimize reproductive success. For instance, the coordination of ovulation and receptivity in females with the activity and wakefulness of males ensures that mating occurs at the most favorable times (Singh and Kumar, 2018).

Circadian rhythms also influence the expression of genes involved in reproductive processes. In Drosophila, the circadian clock in the fat body regulates the rhythmic expression of genes related to metabolism, detoxification, immune response, and steroid hormone regulation. Disruptions in these rhythms, such as through aberrant feeding patterns, can lead to reduced reproductive fitness (Xu et al., 2011).

Furthermore, the presence of clock genes in reproductive tissues suggests that these genes play a significant role in optimizing fertility. Studies in laboratory animals have shown that disruptions in circadian rhythms can adversely affect reproductive outcomes, emphasizing the importance of maintaining proper circadian timing for reproductive health (Kennaway, 2005).

In summary, circadian rhythms are fundamental to the regulation of various behavioral functions in animals, including sleep-wake cycles, feeding and foraging behaviors, and reproductive activities. These rhythms ensure that physiological processes are synchronized with the external environment, thereby enhancing survival and reproductive success. Disruptions in circadian rhythms can lead to significant health and reproductive issues, highlighting the importance of maintaining proper circadian timing in animals.

5 Environmental Influences on Circadian Rhythms

5.1 Light as a primary environmental cue

Light is the most significant environmental cue for regulating circadian rhythms in animals. The circadian system relies heavily on light to synchronize internal clocks with the external environment. In mammals, the central circadian clock located in the suprachiasmatic nuclei (SCN) of the brain is primarily entrained by light signals perceived by the retina. These signals are transmitted to the SCN, which then coordinates peripheral clocks throughout the body to maintain synchrony with the day-night cycle (Dibner et al., 2010; Ashton et al., 2022). The molecular mechanisms underlying this photic entrainment involve complex pathways that integrate photoreception with the transcriptional-translational feedback loops of the circadian clock (Ashton et al., 2022).

Research has shown that light not only influences the timing of circadian rhythms but also affects rhythmic brain function and behavior. For instance, nocturnal rodents exhibit significant changes in brain activity and behavior in response to light exposure, highlighting the critical role of light in modulating circadian rhythms (Gall, 2022). Additionally, disruptions in light exposure, such as light at night, can lead to chronodisruption, which has been linked to various health issues, including neurodegenerative diseases (Gall, 2022).

5.2 Seasonal changes and circadian adjustments

Seasonal changes in day length and temperature necessitate adjustments in circadian rhythms to ensure optimal physiological and behavioral responses. Animals have evolved mechanisms to adapt their circadian clocks to these seasonal variations. For example, the circadian clock in Drosophila is highly plastic, allowing it to adjust to changes in day length and temperature, thereby maintaining proper phase relationships with the environment (Dubruille and Emery, 2008).

In mammals, the circadian clock also plays a crucial role in regulating annual rhythms, such as seasonal reproduction and hibernation. These annual rhythms are influenced by environmental factors like photoperiod and temperature, which affect gene expression, hormone levels, and cellular morphology (Yang et al., 2023). Melatonin, a hormone regulated by the circadian clock, is a key signal for recognizing changes in photoperiod and orchestrating seasonal physiological changes (Yang et al., 2023).

Studies on the blue mussel, Mytilus edulis, have demonstrated that both light and temperature cycles significantly influence the expression of circadian clock genes. These environmental cues help synchronize the mussel's reproductive rhythms with seasonal changes, highlighting the importance of environmental factors in regulating circadian and seasonal rhythms (Chapman et al., 2020).

5.3 The impact of temperature and other abiotic factors

Temperature is another critical abiotic factor that influences circadian rhythms. In many species, temperature cycles can entrain circadian clocks, similar to light. For instance, in Mytilus edulis, temperature cycles have been shown to induce significant changes in the expression of clock genes, even in the absence of light cues (Chapman et al., 2020). This indicates that temperature can serve as a potent zeitgeber, or time cue, for circadian rhythms.

Moreover, environmental chemicals, including natural and anthropogenic compounds, can disrupt circadian rhythms. These circadian disrupters, such as steroid hormones, metals, and pesticides, have been shown to affect the circadian system at both molecular and physiological levels. For example, in zebrafish, exposure to these chemicals can lead to behavioral alterations and disruptions in circadian gene expression (Zheng et al., 2021). Understanding the impact of these abiotic factors is crucial for predicting the consequences of environmental changes on circadian rhythms and overall health.

In summary, environmental factors such as light, seasonal changes, temperature, and chemical pollutants play significant roles in modulating circadian rhythms in animals. These factors influence the synchronization of internal clocks with the external environment, ensuring that physiological and behavioral processes are optimally timed. Continued research in this area is essential for understanding the complex interactions between environmental cues and circadian systems, and for addressing the potential health impacts of circadian disruptions.

6 Adaptive Functions of Circadian Rhythms

6.1 Survival advantages of circadian rhythms

Circadian rhythms confer significant survival advantages to animals by optimizing their physiological and behavioral processes to align with the external environment. These rhythms enable animals to anticipate and prepare for regular environmental changes, such as the day-night cycle, thereby enhancing their ability to forage, reproduce, and avoid predators at the most opportune times. For instance, animals have evolved to forage for food during times when it is most abundant and to be active when predators are least active, thereby reducing the risk of predation (Kriegsfeld et al., 2002; Riede et al., 2017). This synchronization of internal physiological events with external cues ensures that energy-intensive processes are distributed throughout the day, preventing the simultaneous peak of all energetic demands and thus promoting efficient energy use (Kriegsfeld et al., 2002). The evolutionary adaptation of circadian rhythms to environmental cycles underscores their critical role in enhancing the fitness and survival of organisms (Yerushalmi and Green, 2009).

6.2 Circadian rhythms in predator-prey interactions

Circadian rhythms play a crucial role in predator-prey interactions by influencing the timing of activity and rest periods in both predators and prey. Predators often time their hunting activities to coincide with periods when their prey is most vulnerable, while prey species adjust their activity patterns to avoid peak predation times. For example, nocturnal predators hunt at night when their prey is less vigilant, whereas diurnal prey species are active during the day to minimize encounters with nocturnal predators (Kriegsfeld et al., 2002; Riede et al., 2017). This temporal partitioning of activity reduces direct encounters between predators and prey, thereby enhancing the survival chances of both. Additionally, some species exhibit plasticity in their circadian rhythms, allowing them to shift their activity patterns in response to changes in predation pressure or environmental conditions, further highlighting the adaptive significance of these rhythms in predator-prey dynamics (Bloch et al., 2013; Riede et al., 2017).

6.3 Adaptations in circadian rhythms to ecological niches

Circadian rhythms are highly adaptable and can be fine-tuned to match the specific ecological niches that different species inhabit. This adaptability is evident in the diverse activity patterns observed across species living in various habitats, from polar regions with extreme photoperiods to tropical environments with consistent day-night cycles. For instance, animals in polar regions, where the day-night cycle can be absent for extended periods, often exhibit arrhythmic or ultradian activity patterns to cope with the constant environmental conditions (Bloch et al., 2013; Bertolini et al., 2019). High-latitude species, such as certain Drosophila species, have evolved specific clock adaptations that allow them to remain active under constant darkness, demonstrating the flexibility of circadian systems in response to ecological demands (Bertolini et al., 2019). Similarly, herbivores and social animals may exhibit around-the-clock activity patterns during specific life-history stages, such as migration or reproduction, to maximize their fitness in their respective environments (Bloch et al., 2013).

The molecular mechanisms underlying these adaptations involve complex interactions between genetic and environmental factors. For example, the circadian clock network in high-latitude Drosophila species has evolved to support arrhythmic behavior under constant darkness, a trait that is advantageous for survival in polar regions. This plasticity in circadian rhythms allows animals to optimize their physiological and behavioral processes to the unique challenges of their habitats, thereby enhancing their overall fitness and survival (Harmer et al., 2001; Pilorz et al., 2018).

In summary, the adaptive functions of circadian rhythms are multifaceted, encompassing survival advantages, predator-prey interactions, and ecological niche adaptations. These rhythms enable animals to synchronize their internal processes with external environmental cues, optimize their energy use, and adjust their behavior to minimize predation risk and maximize resource acquisition. The evolutionary flexibility of circadian systems underscores their critical role in the survival and fitness of organisms across diverse ecological contexts.

7 Circadian Rhythms in Different Animal Taxa

7.1 Mammals

Circadian rhythms in mammals are governed by a complex interplay of genetic and biochemical mechanisms. The core of the mammalian circadian clock consists of a set of genes, including Clock, Bmal1, Period, and Cryptochrome, which form a transcription-translation feedback loop. This loop is responsible for generating and maintaining the near-24-hour cycles of physiological and behavioral processes (King and Takahashi, 2000; Van Gelder, 2003). The mammalian circadian system is highly adaptive, allowing organisms to synchronize their internal clocks with external environmental cues, such as light and temperature (Harmer et al., 2001; Pilorz et al., 2018).

In mammals, circadian rhythms regulate a wide array of physiological functions, including sleep-wake cycles, hormone secretion, metabolism, and immune responses (Panda, 2016; Pilorz et al., 2018). Disruption of these rhythms, often due to modern lifestyle factors like shift work and exposure to artificial light, has been linked to various health issues, including metabolic disorders, cardiovascular diseases, and mental health conditions (Panda, 2016; Cao, 2023). Experimental studies using animal models, such as mice and hamsters, have been instrumental in elucidating the molecular mechanisms underlying circadian rhythms and their impact on health (Cao, 2023).

7.2 Birds

Birds exhibit circadian rhythms that are crucial for regulating their daily activities, such as feeding, singing, and migration. These rhythms are primarily influenced by the light-dark cycle, which acts as a powerful zeitgeber (time-giver) to synchronize their internal clocks with the external environment (Singh and Kumar, 2018). The avian circadian system shares similarities with that of mammals, including the presence of clock genes and feedback loops that generate rhythmic patterns of gene expression (Harmer et al., 2001).

One of the most fascinating aspects of avian circadian rhythms is their role in seasonal behaviors, such as migration and reproduction. Changes in photoperiod (day length) trigger physiological and behavioral adaptations that prepare birds for long-distance migration or breeding (Singh and Kumar, 2018). For instance, the timing of migration is tightly regulated by circadian clocks, ensuring that birds embark on their journeys at the most favorable times of the year. Additionally, circadian rhythms in birds are known to influence their reproductive cycles, coordinating ovulation and mating behaviors to optimize reproductive success (Singh and Kumar, 2018).

7.3 Invertebrates

Invertebrates, including insects and marine organisms, also exhibit circadian rhythms that regulate various aspects of their physiology and behavior. The molecular mechanisms underlying these rhythms are remarkably conserved across different species, with core clock genes such as Clock, Bmal1, Period, and Timeless playing central roles (King and Takahashi, 2000; Van Gelder, 2003). In Drosophila, for example, the circadian clock consists of interlocked feedback loops involving these genes, which generate rhythmic patterns of gene expression and behavior (Van Gelder, 2003).

Circadian rhythms in invertebrates are essential for coordinating activities such as feeding, mating, and locomotion. In Drosophila, the circadian clock regulates daily patterns of activity and rest, ensuring that the flies are active during the day and rest at night (Van Gelder, 2003). Similarly, marine invertebrates, such as the pico-eukaryotic alga Ostreococcus tauri, possess circadian clocks that regulate their photosynthetic activities and other metabolic processes (O’Neill et al., 2010). Interestingly, recent studies have shown that non-transcriptional mechanisms, such as protein oxidation, also play a significant role in sustaining circadian rhythms in these organisms, highlighting the evolutionary conservation of circadian timekeeping mechanisms (O’Neill et al., 2010).

In summary, circadian rhythms are a fundamental feature of animal life, regulating a wide range of physiological and behavioral processes across different taxa. The molecular mechanisms underlying these rhythms are highly conserved, yet they exhibit remarkable flexibility to adapt to the specific needs and environmental conditions of each species. Understanding these mechanisms provides valuable insights into the evolutionary significance of circadian rhythms and their impact on animal health and behavior.

8 Case Studies

8.1 Circadian rhythms in nocturnal animals

Nocturnal animals exhibit unique adaptations in their circadian rhythms to thrive in environments with minimal light. The master clock in the suprachiasmatic nucleus (SCN) of the hypothalamus plays a crucial role in synchronizing these rhythms with the external light-dark cycle. Interestingly, the SCN's responsiveness to light is maximal during the night for both nocturnal and diurnal species, indicating a shared mechanism despite their opposite activity patterns (Mistlberger and Skene, 2004).

In nocturnal mammals, behavioral arousal during their resting period can act as a potent non-photic synchronizing cue, affecting the SCN's function. This feedback mechanism involves several brain nuclei and neurotransmitters, ultimately altering the molecular function of SCN pacemaker cells. The circadian system's sensitivity to arousal stimuli varies between nocturnal and diurnal species, with nocturnal animals showing reduced light resetting when aroused during their sleep period (Mistlberger and Skene, 2004).

Moreover, some nocturnal animals can exhibit prolonged intervals of activity with attenuated or no overt circadian rhythms without apparent ill effects. This phenomenon is particularly observed in herbivores, animals in polar regions, and during specific life-history stages such as migration or reproduction. The underlying mechanisms suggest that some circadian pacemakers continue to measure time even in the absence of overt rhythms, indicating a potential for chronobiological plasticity (Bloch et al., 2013).

8.2 Impact of circadian disruption in captive animals

Circadian disruption in captive animals can lead to significant physiological and behavioral changes. For instance, studies on mice have shown that sleep restriction can lead to an 80% reduction in circadian transcripts in the brain and profound disruption of the liver transcriptome. These changes include a significant reduction in the circadian regulation of transcription and translation, as well as core clock genes in peripheral tissues (Goede et al., 2018).

In zebra finches, constant light exposure (LL) during development resulted in weight gain, lipid accumulation in the liver, and disrupted circadian gene expression. Despite these disruptions, some birds maintained rhythmic activity, indicating a dissociation between behavior and clock gene rhythms. This suggests that diurnal animals might employ different mechanisms to adapt to constant light environments, which could have implications for understanding metabolic adaptations in urban settings (Prabhat et al., 2020).

Animal models have been instrumental in elucidating the mechanisms of circadian disruption. For example, studies on rodents have shown that timed light exposure can phase-shift locomotor rhythms, with younger male animals being the primary subjects of these studies. This research has highlighted the importance of considering biological variables such as age and sex in understanding photic resetting and its implications for circadian timekeeping (Lee et al., 2021).

8.3 Human influence on animal circadian rhythms

Human activities, particularly in urban environments, have a profound impact on animal circadian rhythms. Increased nighttime illumination and altered light-dark cycles can disrupt the natural circadian rhythms of animals, leading to various health and behavioral issues. For instance, environmental chemicals such as steroid hormones, metals, and pesticides have been shown to disrupt circadian rhythms in fish, affecting their behavior and physiological processes (Zheng et al., 2021). Urban environments with constant light exposure can lead to circadian disruption in animals, as seen in zebra finches exposed to LL. These birds exhibited disrupted circadian gene expression and metabolic changes, highlighting the potential consequences of artificial light on animal health (Prabhat et al., 2020).

Moreover, social stimuli can act as zeitgebers (time cues) for entraining circadian rhythms in mammals. While light is the dominant stimulus, social interactions can also influence circadian behavioral programs by regulating the phase and period of circadian clocks. In humans, social zeitgebers appear weaker compared to light, but they can still affect circadian timing by controlling sleep-wake states and inducing phase shifts through exercise sessions (Mistlberger and Skene, 2004).

In conclusion, the study of circadian rhythms in animals, particularly in the context of nocturnal behavior, captive environments, and human influence, provides valuable insights into the mechanisms and functions of these rhythms. Understanding these interactions is crucial for developing strategies to mitigate the adverse effects of circadian disruption on animal health and behavior.

9 Future Directions in Circadian Rhythm Research

9.1 Emerging technologies in circadian research

The field of circadian rhythm research is poised for significant advancements with the advent of emerging technologies. One promising area is the use of high-throughput sequencing and bioinformatics tools to map circadian gene expression across different tissues and species. For instance, recent studies have utilized comprehensive experimental approaches and computational methods to analyze periodic functional genomics data, revealing dynamic chromatin interactions as a novel regulatory layer underlying circadian gene transcription and behavior (Yeung et al., 2018). Additionally, the development of advanced imaging techniques and real-time monitoring systems allows for the precise tracking of circadian rhythms in live animals, providing deeper insights into the temporal dynamics of circadian regulation (Eckel-Mahan and Sassone-Corsi, 2015).

Another exciting technological advancement is the use of CRISPR-Cas9 gene editing to manipulate circadian genes in animal models. This technology enables researchers to create specific gene knockouts or modifications, thereby elucidating the roles of individual genes in the circadian system (King and Takahashi, 2000). Furthermore, the integration of machine learning algorithms with circadian data sets can help identify previously unrecognized patterns and interactions, offering new avenues for understanding the complexity of circadian networks (Yeung et al., 2018).

9.2 Potential applications in animal conservation and management

Circadian rhythm research holds significant potential for applications in animal conservation and management. Understanding the circadian biology of endangered species can inform conservation strategies by optimizing breeding programs and habitat management to align with the natural rhythms of these animals. For example, knowledge of circadian rhythms can be used to schedule feeding, mating, and other activities to coincide with the animals' peak activity periods, thereby enhancing their overall health and reproductive success (Bloch et al., 2013).

Moreover, circadian research can aid in the management of captive animals by improving their welfare. By mimicking natural light-dark cycles and other environmental cues, zookeepers and wildlife managers can create conditions that support the animals' circadian rhythms, reducing stress and promoting natural behaviors (Matveyenko, 2018). Additionally, understanding the circadian mechanisms underlying migration and hibernation can help in the development of strategies to support these critical life-history stages in wild populations (Bloch et al., 2013).

9.3 Unresolved questions and research gaps

Despite significant progress, several unresolved questions and research gaps remain in the field of circadian rhythm research. One major question is the extent to which circadian rhythms are conserved across different species and how these rhythms have evolved to adapt to specific environmental niches. While some clock components are conserved, their functions can vary widely, reflecting the diverse ecological contexts in which different species operate (Harmer et al., 2001).

Another critical research gap is the understanding of how circadian disruptions contribute to various diseases. Although there is substantial evidence linking circadian misalignment to metabolic disorders, depression, and other health issues, the underlying mechanisms remain poorly understood (Kronfeld-Schor and Einat, 2012). Further research is needed to elucidate the pathways through which circadian disruptions impact physiological processes and to develop interventions that can mitigate these effects.

Additionally, there is a need for more comprehensive studies on the interaction between circadian rhythms and other biological systems, such as the immune system and the microbiome. These interactions are likely to play crucial roles in maintaining overall health and resilience to environmental stressors (Matveyenko, 2018). Finally, the development of better animal models that more closely mimic human circadian rhythms could enhance our understanding of circadian-related diseases and improve the translational potential of circadian research (Kronfeld-Schor and Einat, 2012).

In conclusion, the future of circadian rhythm research is bright, with emerging technologies offering new tools for discovery, and potential applications in conservation and animal management promising to enhance both animal welfare and ecological sustainability. However, addressing the unresolved questions and research gaps will require continued interdisciplinary collaboration and innovative approaches.

10 Concluding Remarks

Circadian rhythms are intrinsic, near-24-hour cycles that regulate various physiological and behavioral processes in animals. These rhythms are generated by a complex interplay of genetic and molecular mechanisms, primarily involving transcription-translation feedback loops. Key genes such as Clock, Bmal1, Period, and Timeless play crucial roles in maintaining these rhythms. The central circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus, acts as a master pacemaker, coordinating peripheral clocks throughout the body. Circadian rhythms are not only influenced by light-dark cycles but also by social cues and environmental factors, which can synchronize or disrupt these rhythms. Additionally, circadian rhythms have significant implications for metabolism, reproduction, and overall health, with disruptions linked to various metabolic diseases.

The study of circadian rhythms extends beyond understanding daily cycles; it provides insights into the fundamental principles of biological timekeeping and its evolutionary significance. The conservation of circadian mechanisms across species, from Drosophila to mammals, underscores the importance of these rhythms in adapting to environmental changes. Circadian rhythms orchestrate a wide range of physiological processes, including sleep-wake cycles, feeding behavior, hormone secretion, and metabolic functions, thereby optimizing energy use and enhancing survival and reproductive success. The interplay between circadian and circannual rhythms further highlights the adaptive strategies organisms employ to cope with seasonal variations, emphasizing the role of environmental cues in shaping biological rhythms.

Understanding circadian rhythms in animals offers profound implications for both basic and applied sciences. Future research should focus on elucidating the molecular and genetic underpinnings of circadian clocks in diverse species and their interactions with environmental and social factors. Investigating the mechanisms of circadian disruption and its link to metabolic and other chronic diseases could pave the way for novel therapeutic strategies. Additionally, exploring the role of circadian rhythms in different life-history stages and ecological contexts will provide a more comprehensive understanding of their adaptive value. As we continue to unravel the complexities of circadian biology, interdisciplinary approaches integrating molecular genetics, physiology, and ecology will be crucial in advancing our knowledge and addressing the broader implications for health and disease management.

Acknowledgements

The authors extend sincere thanks to two anonymous peer reviewers for their feedback on the manuscript.

Conflict of Interest Disclosure

The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

References 

Asher G., and Schibler U., 2011, Crosstalk between components of circadian and metabolic cycles in mammals, Cell Metabolism, 13(2): 125-137.

https://doi.org/10.1016/j.cmet.2011.01.006
PMid:21284980

Ashton A., Foster R., and Jagannath A., 2022, Photic entrainment of the circadian system, International Journal of Molecular Sciences, 23(2): 729.

https://doi.org/10.3390/ijms23020729
PMid:35054913 PMCid:PMC8775994

Bertolini E., Schubert F., Zanini D., Sehadová H., Helfrich-Förster C., and Menegazzi P., 2019, Life at high latitudes does not require circadian behavioral rhythmicity under constant darkness, Current Biology, 29(22): 3928-3936, e3.

https://doi.org/10.1016/j.cub.2019.09.032
PMid:31679928

Bloch G., Barnes B., Gerkema M., and Helm B., 2013, Animal activity around the clock with no overt circadian rhythms: patterns, mechanisms and adaptive value, Proceedings of the Royal Society B: Biological Sciences, 280(1765): 20130019.

https://doi.org/10.1098/rspb.2013.0019
PMid:23825202 PMCid:PMC3712434

Cao T., 2023, A review of animal models of the circadian cycle, Theoretical and Natural Science, 8: 226-229.

https://doi.org/10.54254/2753-8818/8/20240392

Chapman E., Bonsor B., Parsons D., and Rotchell J., 2020, Influence of light and temperature cycles on the expression of circadian clock genes in the mussel Mytilus edulis, Marine Environmental Research, 159: 104960.

https://doi.org/10.1016/j.marenvres.2020.104960
PMid:32250881

Dibner C., Schibler U., and Albrecht U., 2010, The mammalian circadian timing system: organization and coordination of central and peripheral clocks, Annual Review of Physiology, 72(1): 517-549.

https://doi.org/10.1146/annurev-physiol-021909-135821
PMid:20148687

Dreyer A., Martin M., Fulgham C., Jabr D., Bai L., Beshel J., and Cavanaugh D., 2019, A circadian output center controlling feeding: fasting rhythms in Drosophila, PLoS Genetics, 15(11): e1008478.

https://doi.org/10.1371/journal.pgen.1008478
PMid:31693685 PMCid:PMC6860455

Dubruille R., and Emery P., 2008, A plastic clock: how circadian rhythms respond to environmental cues in Drosophila, Molecular Neurobiology, 38: 129-145.

https://doi.org/10.1007/s12035-008-8035-y
PMid:18751931

Eckel-Mahan K., and Sassone-Corsi P., 2013, Metabolism and the circadian clock converge, Physiological reviews, 93(1): 107-135.

https://doi.org/10.1152/physrev.00016.2012
PMid:23303907 PMCid:PMC3781773

Eckel-Mahan K., and Sassone-Corsi P., 2015, Phenotyping circadian rhythms in mice, Current Protocols in Mouse Biology, 5(3): 271-281.

https://doi.org/10.1002/9780470942390.mo140229
PMid:26331760 PMCid:PMC4732881

Gall C., 2022, The effects of light and the circadian system on rhythmic brain function, International Journal of Molecular Sciences, 23(5): 2778.

https://doi.org/10.3390/ijms23052778
PMid:35269920 PMCid:PMC8911243

Goede P., Wefers J., Brombacher E., Schrauwen P., and Kalsbeek A., 2018, Circadian rhythms in mitochondrial respiration, Journal of Molecular Endocrinology, 60(3): R115-R130.

https://doi.org/10.1530/JME-17-0196
PMid:29378772 PMCid:PMC5854864

Guan D., and Lazar M., 2021, Interconnections between circadian clocks and metabolism, The Journal of Clinical Investigation, 131(15): e148278.

https://doi.org/10.1172/JCI148278
PMid:34338232 PMCid:PMC8321578

Harmer S., Panda S., and Kay S., 2001, Molecular bases of circadian rhythms, Annual Review of Cell and Developmental Biology, 17(1): 215-253.

https://doi.org/10.1146/annurev.cellbio.17.1.215
PMid:11687489

Isojima Y., Okumura N., and Nagai K., 2003, Molecular mechanism of mammalian circadian clock, Journal of Biochemistry, 134(6): 777-784.

https://doi.org/10.1093/jb/mvg219
PMid:14769864

Kennaway D., 2005, The role of circadian rhythmicity in reproduction, Human Reproduction Update, 11(1): 91-101.

https://doi.org/10.1093/humupd/dmh054
PMid:15569698

King D., and Takahashi J., 2000, Molecular genetics of circadian rhythms in mammals, Annual Review of Neuroscience, 23(1): 713-742.

https://doi.org/10.1146/annurev.neuro.23.1.713
PMid:10845079

Koop S., and Oster H., 2021, Eat, sleep, repeat-endocrine regulation of behavioural circadian rhythms, The FEBS Journal, 289(21): 6543-6558.

https://doi.org/10.1111/febs.16109
PMid:34228879

Kriegsfeld L., LeSauter J., Hamada T., Pitts S., and Silver R., 2002, Circadian rhythms in the endocrine system, Hormones, Brain and Behavior, 2002: 33-91.

https://doi.org/10.1016/B978-012532104-4/50020-2

Kronfeld-Schor N., and Einat H., 2012, Circadian rhythms and depression: human psychopathology and animal models, Neuropharmacology, 62(1): 101-114.

https://doi.org/10.1016/j.neuropharm.2011.08.020
PMid:21871466

Lee R., Tapia A., Kaladchibachi S., Grandner M., and Fernandez F., 2021, Meta-analysis of light and circadian timekeeping in rodents, Neuroscience & Biobehavioral Reviews, 123: 215-229.

https://doi.org/10.1016/j.neubiorev.2020.12.024
PMid:33513413

Lowrey P., and Takahashi J., 2000, Genetics of the mammalian circadian system: photic entrainment, circadian pacemaker mechanisms, and posttranslational regulation, Annual Review of Genetics, 34(1): 533-562.

https://doi.org/10.1146/annurev.genet.34.1.533
PMid:11092838

Matveyenko A., 2018, Consideration for circadian physiology in rodent research, Physiology, 33(4): 250-251.

https://doi.org/10.1152/physiol.00012.2018
PMid:29873599

Meli A., 2018, Circadian clock: each tissue has its own rhythm, Cardiovascular Research, 114(8): e57-e59.

https://doi.org/10.1093/cvr/cvy098
PMid:30052895

Meyer-Bernstein E., and Sehgal A., 2001, Book review: molecular regulation of circadian rhythms in drosophila and mammals, The Neuroscientist, 7(6): 496-505.

https://doi.org/10.1177/107385840100700606
PMid:11765127

Mistlberger R., and Skene D., 2004, Social influences on mammalian circadian rhythms: animal and human studies, Biological Reviews, 79(3): 533-556.

https://doi.org/10.1017/S1464793103006353
PMid:15366762

Mohawk J., Green C., and Takahashi J., 2012, Central and peripheral circadian clocks in mammals, Annual Review of Neuroscience, 35(1): 445-462.

https://doi.org/10.1146/annurev-neuro-060909-153128
PMid:22483041 PMCid:PMC3710582

O’Neill J., Ooijen G., Dixon L., Troein C., Corellou F., Bouget F., Reddy A., and Millar A., 2010, Circadian rhythms persist without transcription in a eukaryote, Nature, 469(7331): 554-558.

https://doi.org/10.1038/nature09654
PMid:21270895 PMCid:PMC3040569

Panda S., 2016, Circadian physiology of metabolism, Science, 354(6315): 1008-1015.

https://doi.org/10.1126/science.aah4967
PMid:27885007 PMCid:PMC7261592

Partch C., Green C., and Takahashi J., 2014, Molecular architecture of the mammalian circadian clock, Trends in Cell Biology, 24(2): 90-99.

https://doi.org/10.1016/j.tcb.2013.07.002
PMid:23916625 PMCid:PMC3946763

Pilorz V., Helfrich-Förster C., and Oster H., 2018, The role of the circadian clock system in physiology, Pflügers Archiv-European Journal of Physiology, 470: 227-239.

https://doi.org/10.1007/s00424-017-2103-y
PMid:29302752

Pitsillou E., Liang J., Hung A., and Karagiannis T., 2020, The circadian machinery links metabolic disorders and depression: a review of pathways, proteins and potential pharmacological interventions, Life Sciences, 265: 118809.

https://doi.org/10.1016/j.lfs.2020.118809
PMid:33249097

Prabhat A., Malik I., Jha N., Bhardwaj S., and Kumar V., 2020, Developmental effects of constant light on circadian behaviour and gene expressions in zebra finches: insights into mechanisms of metabolic adaptation to aperiodic environment in diurnal animals, Journal of Photochemistry and Photobiology. B, Biology, 211: 111995.

https://doi.org/10.1016/j.jphotobiol.2020.111995
PMid:32836050

Riede S., Vinne V., and Hut R., 2017, The flexible clock: predictive and reactive homeostasis, energy balance and the circadian regulation of sleep–wake timing, Journal of Experimental Biology, 220(5): 738-749.

https://doi.org/10.1242/jeb.130757
PMid:28250173

Robles M., Humphrey S., and Mann M., 2017, Phosphorylation Is a Central Mechanism for Circadian Control of Metabolism and Physiology, Cell metabolism, 25(1): 118-127.

https://doi.org/10.1016/j.cmet.2016.10.004
PMid:27818261

Sanchez R., Kalume F., and Iglesia H., 2021, Sleep timing and the circadian clock in mammals: past, present and the road ahead, Seminars in Cell & Developmental Biology, 126: 3-14.

https://doi.org/10.1016/j.semcdb.2021.05.034
PMid:34092510 PMCid:PMC8800593

Schmutz I., Ripperger J., Baeriswyl-Aebischer S., and Albrecht U., 2010, The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors, Genes & Development, 24(4): 345-357.

https://doi.org/10.1101/gad.564110
PMid:20159955 PMCid:PMC2816734

Singh S., and Kumar S., 2018, Circadian rhythm and their significance in relation to physiological functions of animals: a review, Journal of Entomology and Zoology Studies, 6: 1861-1866.

Takahashi J., 2015, Molecular components of the circadian clock in mammals, Diabetes, 17: 6-11.

https://doi.org/10.1111/dom.12514
PMid:26332962 PMCid:PMC4560116

Tsang A., Barclay J., and Oster H., 2013, Interactions between endocrine and circadian systems, Journal of Molecular Endocrinology, 52(1): R1-R16.

https://doi.org/10.1530/JME-13-0118
PMid:23997239

Van Gelder R.N. , 2003, Circadian rhythms in animals: a canonical connections map, Science Signaling, 2003(194): cm8.

https://doi.org/10.1126/stke.2003.194.cm8

Xu K., Diangelo J., Hughes M., Hogenesch J., and Sehgal A., 2011, The circadian clock interacts with metabolic physiology to influence reproductive fitness, Cell Metabolism, 13(6): 639-654.

https://doi.org/10.1016/j.cmet.2011.05.001
PMid:21641546 PMCid:PMC3152999

Yang Y., Chu M., and Liu Q., 2023, The mechanism of circadian clock and its influence on animal circannual rhythm, Yi chuan=Hereditas, 45(5): 409-424.

https://doi.org/10.16288/j.yczz.23-008

Yerushalmi S., and Green R., 2009, Evidence for the adaptive significance of circadian rhythms, Ecology Letters, 12(9): 970-981.

https://doi.org/10.1111/j.1461-0248.2009.01343.x
PMid:19566794

Yeung J., and Naef F., 2018, Rhythms of the genome: circadian dynamics from chromatin topology, tissue-specific gene expression, to behavior, Trends in Genetics, 34(12): 915-926.

https://doi.org/10.1016/j.tig.2018.09.005
PMid:30309754

Zheng X., Zhang K., Zhao Y., and Fent K., 2021, Environmental chemicals affect circadian rhythms: an underexplored effect influencing health and fitness in animals and humans, Environment International, 149: 106159.

https://doi.org/10.1016/j.envint.2020.106159
PMid:33508534