Circadian Rhythm: The 24-Hour Biological Clock
The circadian clock runs at ~24.2 hours endogenously; the suprachiasmatic nucleus resets it daily via retinal light input; disruption of this rhythm increases metabolic disease risk by 20–40%.
| Measure | Value | Unit | Notes |
|---|---|---|---|
| Endogenous period (tau) | 24.2 | hours | Czeisler et al. 1999; range 23.5–24.7h across individuals |
| Core temperature nadir | ~4–6am | clock time | Lowest body temperature; worst cognitive performance; coincides with peak melatonin |
| Cortisol peak | 30–60 min after waking | post-waking | Cortisol awakening response; strongest circadian signal for morning type |
| Melatonin onset (DLMO) | ~2h before habitual sleep | pre-sleep | Dim-light melatonin onset; clinical marker of circadian phase |
| Circadian misalignment metabolic risk | 20–40 | % increased risk | Metabolic syndrome, insulin resistance, cardiovascular risk with shift work |
| Light to SCN reset per day | 1–2 | hours maximum | The circadian clock can advance/delay ~1–2h per day via photic entrainment |
The Circadian Clock System
All known life on Earth that has been tested — bacteria, fungi, plants, flies, fish, and humans — maintains an endogenous timekeeping mechanism with a period close to 24 hours. In humans, this biological clock runs at approximately 24.2 hours (Czeisler et al., 1999) and must be reset daily by environmental time cues, primarily the light-dark cycle.
The circadian system evolved to align physiology and behavior with the predictable 24-hour solar cycle. It drives not just the sleep-wake cycle but virtually every physiological parameter: body temperature, hormone secretion, immune function, cell division timing, metabolic rate, blood pressure, and cognitive performance all follow circadian rhythms.
Molecular Mechanism
The core molecular oscillator involves a transcription-translation feedback loop:
- CLOCK:BMAL1 heterodimer activates transcription of PER (Period) and CRY (Cryptochrome) genes
- PER and CRY proteins accumulate, then form complexes that enter the nucleus
- PER:CRY complexes inhibit CLOCK:BMAL1, repressing their own transcription
- PER and CRY are degraded (via CKIε/δ phosphorylation and ubiquitin-proteasome pathway)
- Inhibition lifts, and the cycle begins again — taking ~24 hours
This cell-autonomous oscillator operates in virtually every cell in the body, not just the SCN. The SCN acts as the master pacemaker, synchronizing peripheral clocks through neural signals (autonomic nervous system), hormonal signals (cortisol, glucocorticoids), and temperature rhythms.
Circadian Regulation of Sleep
The two-process model (Borbély, 1982) describes sleep timing as the interaction of:
- Process C: the circadian “wake-promoting” signal from the SCN, which rises during the day and falls at night
- Process S: the homeostatic sleep pressure signal (adenosine accumulation)
Sleep onset occurs when circadian wake-promotion falls sufficiently and sleep pressure is high enough. The circadian system also actively promotes wakefulness in the late afternoon (“wake maintenance zone”) — explaining why people feel alert before bedtime despite many hours awake.
Consequences of Circadian Disruption
Shift work, jet lag, and irregular sleep schedules cause circadian misalignment — the biological clock is out of phase with the environmental and behavioral schedule. Scheer et al. (2009) demonstrated that even 10 days of circadian misalignment in controlled laboratory conditions caused:
- 20–40% increased postprandial glucose and insulin resistance
- Elevated blood pressure
- Reduced leptin (appetite-suppressing hormone)
- Mood disturbance
Epidemiological studies of shift workers show 40% increased risk of type 2 diabetes, 35% increased cardiovascular disease risk, and 50% increased risk of breast cancer compared to day workers, after controlling for confounders.
Related Pages
Sources
- Czeisler CA et al. — Stability, precision, and near-24-hour period of the human circadian pacemaker. Science (1999)
- Pittendrigh CS — Circadian rhythms and the circadian organization of living systems. Cold Spring Harb Symp (1960)
- Moore RY & Eichler VB — Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res (1972)
- Scheer FA et al. — Adverse metabolic and cardiovascular consequences of circadian misalignment. PNAS (2009)
Frequently Asked Questions
What controls circadian rhythm?
The primary circadian pacemaker is the suprachiasmatic nucleus (SCN), a pair of hypothalamic structures containing ~20,000 neurons. The SCN's self-sustaining molecular oscillator (CLOCK/BMAL1 transcription factors, PER/CRY negative feedback) runs at ~24.2 hours and is synchronized to exactly 24 hours by daily light exposure via the retinohypothalamic tract.
Can circadian rhythm be permanently damaged?
Severe and prolonged circadian disruption (as in long-term shift work) is associated with lasting metabolic and cognitive impairments, but the molecular oscillator itself is robust. Re-entrainment to a regular light-dark cycle can restore normal rhythms over 1–2 weeks, though some shift workers retain elevated metabolic risk even after stopping shift work.
How does light reset the circadian clock?
Light exposure activates intrinsically photosensitive retinal ganglion cells (ipRGCs) containing the photopigment melanopsin (peak sensitivity 480nm blue light). These cells project via the retinohypothalamic tract to the SCN, driving immediate-early gene expression and shifting the molecular clock phase. Morning light advances the clock; evening light delays it.