Circadian Rhythm

The clock's molecular machinery: transcriptional-translational loops with genes BMAL1, CLOCK, PER1-3, CRY1-2 oscillating with ~24-hour period. Their discovery merited the 2017 Nobel Prize in Medicine (Hall, Rosbash, Young).

Peripheral clocks: each organ has its own molecular clock normally synchronised with the central SCN. 'Circadian desynchrony' (social jet lag, shift work, eating outside the optimal window) decouples peripheral clocks from the central one, causing metabolic, immune, and endocrine dysregulation.

Consequences of chronic circadian disruption: Metabolic: insulin resistance, obesity, type 2 diabetes, MAFLD. Cardiovascular: hypertension, higher infarct and arrhythmia incidence. Immune: poorer vaccine response, increased infection susceptibility, chronic inflammation. Cognitive: memory impairment, increased Alzheimer's risk. Oncological: IARC classified night shift work as 'probable carcinogen' (group 2A).

Circadian alignment protocol (chronobiohacking): Morning: direct natural light exposure within first 30 min after waking (effect on melatonin, cortisol, and dopamine much greater than any supplement). Day: meals in an 8-12 h window (TRE), preferentially aligned with daylight. Afternoon: progressive reduction of artificial blue light exposure 2-3 h before sleep. Night: total darkness for sleep (target <0.1 lux in bedroom), cool temperature (18-19°C), consistent timing. Daily consistency: keep the same sleep hours all 7 days of the week (including weekends).