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1. Circadian rhythms regulate every aspect of our biology and health

Our bodies need the correct materials in the right place, in the right amount, at the right time of day, and a clock anticipates and delivers these different needs.

Ubiquitous biological clocks. Circadian rhythms are 24-hour cycles that regulate nearly all physiological processes in humans and other organisms. These rhythms are generated by a master clock in the brain's suprachiasmatic nuclei (SCN), as well as peripheral clocks in organs and tissues throughout the body. The SCN coordinates these peripheral clocks to optimize biological functions.

Evolutionary adaptation. Circadian rhythms evolved as an adaptation to the Earth's 24-hour light-dark cycle. They allow organisms to anticipate and prepare for predictable daily changes in the environment. For example, human body temperature, cortisol levels, and cognitive performance all show daily rhythms that align with typical wake and sleep times.

Health implications. Proper circadian timing is crucial for health. Disruption of circadian rhythms has been linked to numerous health problems, including:

• Metabolic disorders
• Cardiovascular disease
• Cancer
• Mood disorders
• Cognitive decline

2. Light is the primary zeitgeber for synchronizing our body clocks

Although light is the dominant signal to entrain the clock, exercise and eating at specific times can also influence entrainment.

Light detection. The eyes contain specialized photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGCs) that detect environmental light and send signals directly to the SCN. These cells are most sensitive to blue light, which is prevalent at dawn and dusk.

Entrainment mechanism. Light exposure at different times of day has varying effects on the circadian system:

• Morning light advances the clock (shifts it earlier)
• Evening light delays the clock (shifts it later)
• Midday light has minimal effect

Modern lighting challenges. Artificial lighting, especially from screens at night, can disrupt natural circadian entrainment. While the effects of typical screen use are often overstated, excessive evening light exposure can delay sleep timing. Strategies to mitigate this include:

• Increasing daytime light exposure, especially in the morning
• Dimming lights and using warmer color temperatures in the evening
• Using blue light filters on devices at night

3. Sleep and circadian rhythm disruption (SCRD) has profound health consequences

We are, of course, not able to do what we want at whatever time we choose. Our biology is governed by a 24-hour biological clock that advises us when it is the best time to sleep, eat, think, and undertake a myriad of other essential tasks.

Widespread problem. SCRD is increasingly common in modern societies due to factors like artificial lighting, shift work, and jet lag. It affects people of all ages, from teenagers to the elderly.

Health impacts. The consequences of chronic SCRD include:

• Increased risk of obesity, diabetes, and cardiovascular disease
• Impaired cognitive function and increased accident risk
• Higher rates of certain cancers
• Weakened immune function
• Mental health issues like depression and anxiety

Mechanisms. SCRD disrupts the normal functioning of many biological systems:

• Hormonal imbalances (e.g., cortisol, melatonin)
• Metabolic dysregulation
• Inflammatory responses
• Impaired cellular repair processes

4. Night shift work and jet lag are major disruptors of circadian rhythms

No matter how many years a shift worker spends on permanent night shifts, nearly all (97 per cent) of night shift workers remain synchronized to daytime.

Shift work challenges. Night shift workers face severe circadian misalignment:

• Forced to be awake when their bodies are primed for sleep
• Trying to sleep when their circadian system promotes wakefulness
• Exposure to light at night further disrupts entrainment

Health consequences. Long-term night shift work is associated with:

• Increased risk of cardiovascular disease, diabetes, and certain cancers
• Higher rates of workplace accidents and errors
• Psychological distress and social isolation

Jet lag effects. Rapid travel across time zones causes temporary circadian misalignment:

• Symptoms include fatigue, insomnia, digestive issues, and cognitive impairment
• Recovery typically takes about one day per time zone crossed
• Eastward travel is generally more difficult than westward travel

Mitigation strategies. While not perfect, some approaches can help:

• Strategic light exposure and avoidance
• Melatonin supplementation (with caveats)
• Careful scheduling of sleep, meals, and activity

5. Proper timing of eating and exercise is crucial for metabolic health

When we encounter light around dusk and in the early evening this will delay the clock in the SCN, and the effect is to make us go to bed later and get up later the next day. By contrast, early-morning light will have the opposite effect, advancing the clock, making us go to bed and get up earlier.

Chrononutrition. The timing of food intake significantly affects metabolism:

• Eating later in the day is associated with poorer glucose tolerance and weight gain
• Skipping breakfast can worsen glucose control
• Time-restricted feeding (limiting food intake to a shorter daily window) may have metabolic benefits

Exercise timing. The effects of exercise vary throughout the day:

• Morning exercise may be best for fat burning
• Afternoon/evening exercise typically allows for peak athletic performance
• Very late evening exercise can potentially disrupt sleep

Circadian regulation. Both eating and exercise can act as zeitgebers to help entrain peripheral clocks:

• Morning exercise can help advance circadian timing
• Consistent meal timing can help regulate metabolic rhythms

Individual differences. Chronotype (natural tendency towards morningness or eveningness) can influence optimal timing for both eating and exercise. What works best may vary between individuals.

6. Adolescents have a biologically later chronotype that clashes with early school start times

Adolescents, therefore, get less sleep but probably need just as much sleep as before puberty.

Biological shift. During puberty, adolescents experience a delay in their circadian timing:

• Melatonin release occurs later in the evening
• Natural tendency to fall asleep and wake up shifts later

Societal mismatch. Early school start times conflict with this biological shift:

• Many teens are forced to wake up during their biological night
• This leads to chronic sleep deprivation and "social jet lag"

Consequences. Insufficient and mistimed sleep in adolescents is associated with:

• Poorer academic performance
• Increased risk of depression and anxiety
• Higher rates of car accidents
• Obesity and metabolic issues

Potential solutions. Addressing this mismatch could involve:

• Delaying school start times (which has shown benefits in some studies)
• Educating teens about sleep hygiene and circadian rhythms
• Increasing morning light exposure to help advance circadian timing

7. Aging affects sleep patterns and circadian rhythms

As we age, we also become more morning types and our sleep duration reduces. It seems that the circadian driver of sleep and the processes that give rise to our sleep pressure become 'sloppier' and less able to control the sleep/wake cycle with its earlier precision.

Age-related changes. Common sleep alterations in older adults include:

• Earlier sleep timing (shift towards morningness)
• Reduced total sleep time
• More fragmented sleep with increased awakenings
• Less slow-wave sleep and REM sleep

Circadian alterations. The circadian system also changes with age:

• Reduced amplitude of circadian rhythms
• Earlier timing of circadian-controlled processes
• Decreased sensitivity to light for entrainment

Health implications. These changes can contribute to:

• Increased daytime sleepiness
• Higher risk of falls and accidents
• Cognitive decline and mood disorders

Management strategies. Approaches to improve sleep in older adults:

• Maintain consistent sleep-wake schedules
• Increase daytime light exposure and physical activity
• Address medical conditions that may disrupt sleep (e.g., nocturia, sleep apnea)

8. The immune system has strong circadian regulation

We now appreciate that every aspect of the immune response is being regulated by the circadian system.

Daily rhythms. Many aspects of immune function show circadian variation:

• Levels of immune cells in the blood
• Production of inflammatory mediators
• Susceptibility to infection

Circadian control. The circadian system regulates immune function through:

• Direct innervation of immune organs by the autonomic nervous system
• Hormonal signals (e.g., cortisol)
• Intrinsic clocks within immune cells

Implications. Understanding these rhythms has potential clinical applications:

• Timing vaccinations for optimal immune response
• Scheduling cancer treatments to minimize side effects
• Managing inflammatory conditions like rheumatoid arthritis

SCRD and immunity. Disruption of circadian rhythms can impair immune function:

• Increased susceptibility to infections
• Altered inflammatory responses
• Potential link to autoimmune disorders

9. Many medications are more effective when timed with circadian rhythms

As discussed above, although drugs are being developed that restore circadian rhythms to cells to decrease tumour growth, the current non-surgical approaches to attack cancer deploy a range of anti-cancer drugs or use some form of radiation.

Chronopharmacology. The effectiveness and side effects of many drugs vary with circadian timing:

• Blood pressure medications are often more effective when taken at night
• Some cancer treatments have reduced side effects when timed appropriately

Mechanisms. Circadian variation in drug effects can be due to:

• Changes in drug absorption, metabolism, or excretion
• Fluctuations in the expression or activity of drug targets
• Circadian rhythms in the biological processes being treated

Clinical applications. Timing considerations for various treatments:

• Statins: Some are more effective when taken in the evening
• Aspirin for cardiovascular protection: May be best taken at night
• Chemotherapy: Timing can potentially reduce side effects and improve efficacy

Challenges. Implementing chronotherapy in clinical practice faces obstacles:

• Individual variation in circadian timing
• Practical issues with medication scheduling
• Limited awareness among healthcare providers

10. New circadian-based therapies show promise for treating disorders

Currently research is being undertaken in laboratories around the world to develop new drugs to address SCRD that are based upon our recent and emerging knowledge of how circadian rhythms are generated and regulated at a molecular level.

Targeting the clock. Emerging therapies aim to:

• Restore disrupted circadian rhythms
• Enhance the amplitude of circadian oscillations
• Shift the timing of circadian rhythms

Potential applications. Circadian-based treatments could help with:

• Sleep disorders (e.g., non-24-hour sleep-wake disorder in the blind)
• Metabolic disorders
• Mood disorders
• Neurodegenerative diseases

Approaches. Various strategies are being explored:

• Small molecule drugs targeting clock proteins
• Light therapy optimization
• Timed delivery of existing medications

Challenges. Developing effective circadian therapies involves:

• Understanding individual variation in circadian biology
• Balancing efficacy with potential side effects
• Integrating treatments into patients' daily lives

Last updated: September 8, 2024