Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.

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Stability, Precision, and Near-24-Hour Period of the Human Circadian Pacemaker

1 Non-image forming, irradiance-dependent responses mediated by the human eye include synchronisation of the circadian axis and suppression of pineal melatonin production The retinal photopigment(s) transducing these light responses in humans have not been characterised 2 Using the ability of light to suppress nocturnal melatonin production, we aimed to investigate its spectral sensitivity and produce an action spectrum Melatonin suppression was quantified in 22 volunteers in 215 light exposure trials using monochromatic light (30 min pulse administered at circadian time (CT) 16-18) of different wavelengths (lambda(max) 424, 456, 472, 496, 520 and 548 nm) and irradiances (07-650 microW cm(-2)) 3 At each wavelength, suppression of plasma melatonin increased with increasing irradiance Irradiance-response curves (IRCs) were fitted and the generated half-maximal responses (IR(50)) were corrected for lens filtering and used to construct an action spectrum 4 The resulting action spectrum showed unique short-wavelength sensitivity very different from the classical scotopic and photopic visual systems The lack of fit (r(2) or =073) Of these, the best fit was to the rhodopsin template with lambda(max) 459 nm (r(2) = 074) 5 Our data strongly support a primary role for a novel short-wavelength photopigment in light-induced melatonin suppression and provide the first direct evidence of a non-rod, non-cone photoreceptive system in humans

An action spectrum for melatonin suppression: evidence for a novel non‐rod, non‐cone photoreceptor system in humans

Of the many health-related effects of shift work, disturbed sleep is the most common. This review describes the main observed effects of the three principal shifts (night, morning and afternoon) on patterns of sleep and wakefulness. The mechanism of sleep disruption in relation to circadian rhythms and the specific impact of aspects of shift organization (speed and direction of rotation) are discussed. The most troublesome acute symptoms are difficulty getting to sleep, shortened sleep and somnolence during working hours that continues into successive days off. These are only partially amenable to amelioration by manipulating shift patterns. However, there is no clear indication that chronic sleep problems result from long-term shift work.

/pdf/shift-work-and-disturbed-sleep-wakefulness-10nmtuzswu.pdf

Shift work and disturbed sleep/wakefulness.

The response of the human circadian pacemaker to light was measured in 45 resetting trials. Each trial consisted of an initial endogenous circadian phase assessment, a three-cycle stimulus which included 5 hours of bright light per cycle, and a final phase assessment. The stimulus induced strong (type 0) resetting, with responses highly dependent on the initial circadian phase of light exposure. The magnitude and direction of the phase shifts were modulated by the timing of exposure to ordinary room light, previously thought to be undetectable by the human pacemaker. The data indicate that the sensitivity of the human circadian pacemaker to light is far greater than previously recognized and have important implications for the therapeutic use of light in the management of disorders of circadian regulation.

https://science.sciencemag.org/content/sci/244/4910/1328.full.pdf

Bright light induction of strong (type 0) resetting of the human circadian pacemaker.

A physiological dose of orally administered melatonin shifts circadian rhythms in humans according to a phase-response curve (PRC) that is nearly opposite in phase with the PRCs for light exposure: melatonin delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening. The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel. The human melatonin PRC also provides the strongest evidence to date for a function of endogenous melatonin and its suppression by light in augmenting entrainment of circadian rhythms by the light-dark cycle.

Melatonin shifts human circadian rhythms according to a phase-response curve.

Human circadian rhythms were once thought to be insensitive to light, with synchronization to the 24-hour day accomplished either through social contacts or the sleep-wake schedule. Yet the demonstration of an intensity-dependent neuroendocrine response to bright light has led to renewed consideration of light as a possible synchronizer of the human circadian pacemaker. In a laboratory study, the output of the circadian pacemaker of an elderly woman was monitored before and after exposure to 4 hours of bright light for seven consecutive evenings, and before and after a control study in ordinary room light while her sleep-wake schedule and social contacts remained unchanged. The exposure to bright light in the evening induced a 6-hour delay shift of her circadian pacemaker, as indicated by recordings of body temperature and cortisol secretion. The unexpected magnitude, rapidity, and stability of the shift challenge existing concepts regarding circadian phase-resetting capacity in man and suggest that exposure to bright light can indeed reset the human circadian pacemaker, which controls daily variations in physiologic, behavioral, and cognitive function.

https://science.sciencemag.org/content/sci/233/4764/667.full.pdf

WO Freitag

Papers

Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle.