Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption

doi:10.1016/j.lfs.2017.02.008

Life Sciences

Volume 173, 15 March 2017, Pages 94-106

https://doi.org/10.1016/j.lfs.2017.02.008 Get rights and content

Abstract

Exposure to Artificial Light At Night (ALAN) results in a disruption of the circadian system, which is deleterious to health. In industrialized countries, 75% of the total workforce is estimated to have been involved in shift work and night work. Epidemiologic studies, mainly of nurses, have revealed an association between sustained night work and a 50–100% higher incidence of breast cancer. The potential and multifactorial mechanisms of the effects include the suppression of melatonin secretion by ALAN, sleep deprivation, and circadian disruption.

Shift and/or night work generally decreases the time spent sleeping, and it disrupts the circadian time structure. In the long run, this desynchronization is detrimental to health, as underscored by a large number of epidemiological studies that have uncovered elevated rates of several diseases, including cancer, diabetes, cardiovascular risks, obesity, mood disorders and age-related macular degeneration. It amounts to a public health issue in the light of the very substantial number of individuals involved. The IARC has classified shift work in group 2A of “probable carcinogens to humans” since “they involve a circadian disorganization”. Countermeasures to the effects of ALAN, such as melatonin, bright light, or psychotropic drugs, have been proposed as a means to combat circadian clock disruption and improve adaptation to shift and night work. We review the evidence for the ALAN impacts on health. Furthermore, we highlight the importance of an in-depth mechanistic understanding to combat the detrimental properties of exposure to ALAN and develop strategies of prevention.

Section snippets

Introduction: The internal clock and the circadian system

Circadian rhythms are endogenous rhythms with a periodicity of approximately 24 h (24 ± 4 h). They are widespread and regulate most, if not all, of the major physiological systems in mammals. Circadian rhythms are unquestionably the most studied in the literature though other periods exist that range from milliseconds (i.e. ultradian rhythms, for which the period extends from milliseconds to 20 h) to a year (i.e. infradian rhythms, for which the period extends from 28 h to a year) [1]. Circadian

Light control of melatonin secretion

The circadian system in human beings is a complex entity that starts in the eye and that terminates in the pineal gland, which produces melatonin (5-methoxy-N-acetyltryptamine), a neurohormone essential for functioning of the clock. In humans, melatonin is secreted during the dark phase of the light–dark cycle. Daytime melatonin levels are hence comparatively very low. Light is considered to be the most potent circadian synchronizer for humans, although non-photic time cues, such as meal times,

Artificial light at night disrupts the circadian system

In order to accommodate production demands e.g. machines working 24/24 h, cost saving procedures, or specific issues related to security, approximately 20% of the working population in industrialized countries is engaged in shift and/or night work. This type of employment hence exposes a large number of workers to unusual light-dark cycles. Indeed, in our modern industrialized societies, regular 08 h to 17 h working hours for 5 days a week have become relatively rare (25%) compared to so-called

Shift work, light at night and cancer risk

First hypothesized by Stevens (88), the relationship between exposure to light during shift and/or night work and the occurrence of cancer in workers has been the subject of numerous scientific studies [reviews in e.g. [40], [41], [42]].

Mechanistic approach of ALAN effects in cancer

Various mechanisms have been proposed to explain the effects of light at night on cancer, of which three seem to be essential in impacting various levels of the organism's metabolism: inhibition of night time secretion of melatonin by light, sleep deprivation, and chronodisruption. The reported rise in cancer risk may be a consequence of one -or most probably simultaneous effects- of these three major mechanisms.

Epidemiology

Based on the prospective cohort study of the Nurses' Health Studies, a longer duration of rotating night work was associated with a small yet statistically significant absolute increase in the risk of coronary heart disease [136]. In a systematic review and meta-analysis shift work was significantly associated with myocardial infarction (RR 1.23), ischaemic stroke (RR 1.05), coronary events (RR 1.24) but was not associated with increased rates of mortality (whether vascular cause specific or

Circadian misalignment and diabetes

ALAN appears to favor cardio-metabolic risks [141] which are themselves risk factors for cancers.

Epidemiology

The association of exposure to light at night and being overweight has been found statistically significant [156] in a study using data on countries worldwide (satellite images of night time illumination). Another study of the same kind in South Korea provided epidemiological evidence that ALAN is moderately but significantly associated with obesity and various sleep health issues such as delayed sleep pattern, short sleep duration, insomnia and habitual snoring [157]. Besides, sleeping < 6 h

Epidemiology

Exposure to light at night may impair cognitive performances and induce excessive sleepiness and mood changes associated with the work schedule. Shift work has been associated with impaired cognition and the association was stronger for exposures lasting > 10 years [171]. Shift workers are at higher risks of fatigue, anxiety and depressive symptoms than day workers. This can result in absenteeism and a decline in work productivity [172], [173], [174].

A subsample of individuals (21–73 years old),

Phototoxicity

Age related macular degeneration (AMD), the leading cause of blindness in subjects older than 65 years of age, is a complex neurodegenerative visual disorder caused by the loss of retinal pigmented epithelium (RPE) cells and the light-sensitive photoreceptor cells that they support. The severe visual loss affects around 12% of the population of industrialized countries. Among the potential risk factors that have been documented in this multifactorial disorder, genetic factors are major with the

Methodological limitations of the studies

Some inconsistencies in results of the different studies devoted to the effects of ALAN on cancer risk are related to the fact that the definition of shift work and night work is itself different from a country to another which leads to differences in exposure classification and exposure contrast across studies and makes it difficult to compare and interpret results, and conduct meta-analyses [187]. Shift work and night work are characterized by a specific set of factors, and these should be

Preventive measures to combat circadian disruption and alleviate circadian misalignment

One of the long-term aims of researchers is to counter circadian misalignment and reduce its resulting deleterious effects on health. Testing has involved agents that are likely to resynchronize the clock, such as light and melatonin, as well as specific psychotropic medications with the aim of improving sleep, or conversely to enhance alertness, depending on the work requirements [188].

Conclusions and future perspectives

Approximately 75% of the active population in industrialized countries, work atypical hours; that is to say outside of the so-called normal let us say 08 h to 17 h business hours. By exposing workers to artificial light at night, shift and/or night work decreases the time spent sleeping, and it disrupts the circadian structure, the sleep cycle, social life, and meal times. This results in a perturbation of the functioning of the biological clock that is often called “social jet lag” because of

Conflict of interest

The authors declare that they have no conflict of interest.

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Review articleAssociation between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption

Abstract

Section snippets

Introduction: The internal clock and the circadian system

Light control of melatonin secretion

Artificial light at night disrupts the circadian system

Shift work, light at night and cancer risk

Mechanistic approach of ALAN effects in cancer

Epidemiology

Circadian misalignment and diabetes

Epidemiology

Epidemiology

Phototoxicity

Methodological limitations of the studies

Preventive measures to combat circadian disruption and alleviate circadian misalignment

Conclusions and future perspectives

Conflict of interest

Brain Res. Cogn. Brain Res.

Brain Res. Cogn. Brain Res.

Neuron

Methods Enzymol.

Curr. Biol.

J. Physiol. Paris

Sleep Med. Rev.

Life Sci.

Exp. Gerontol.

Lancet Oncol.

Eur. J. Cancer

Life Sci.

Eur. J. Cancer

Cancer Epidemiol.

Lancet

Cancer Lett.

Properties, entrainment, and physiological functions of mammalian peripheral oscillators

J. Biol. Rhythm.

Peripheral circadian oscillators in mammals

Handb. Exp. Pharmacol.

Advances in understanding the peripheral circadian clocks

FASEB J.

Melatonin biosynthesis in the mammalian pineal gland

Experientia

Human tau in an ultradian light-dark cycle

J. Biol. Rhythm.

Sex difference in the near-24-hour intrinsic period of the human circadian timing system

Proc. Natl. Acad. Sci. U. S. A.

Photic influences on the developing mammal

Characteristics of circadian clocks

Clinical implications of the melatonin phase response curve

J. Clin. Endocrinol. Metab.

Millisecond flashes of light phase delay the human circadian clock during sleep

J. Biol. Rhythm.

Sensitivity of thehuman circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

J. Physiol.

Human responses to bright light of different durations

J. Physiol.

Phototransduction by retinal ganglion cells that set the circadian clock

Science

Damage of photoreceptor- derived cells in culture induced by light emitting diode-derived blue light

Sci. Rep.

Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness

Proc. Natl. Acad. Sci. U. S. A.

Disruption of the circadian system by environmental factors: effects of hypoxia, magnetic fields and general anesthetic agents

Adv. Drug Deliv. Rev.

Synchronisation et dyschronisme des rythmes circadiens humains

Pathol. Biol.

Interindividual differences in the flexibility of human temporal organization: pertinence to jet lag and shiftwork

Chronobiol. Int.

Shift work: coping with the biological clock

Occup. Med. (Lond.)

The effects of extended working hours on health and social well being: a comparative analysis of four independent samples

Chronobiol. Int.

Circadian time organization of professional firemen: desynchronization-tau differing from 24.0 hours-documented by longitudinal self-assessment of 16 variables

Chronobiol. Int.

Chronobiologic perspectives of black time - accident risk is greatest at night: an opinion paper

Chronobiol. Int.

Jet lag

BMJ Clin. Evid.

Circadian rhythm abnormalities in totally blind people: incidence and clinical significance

J. Clin. Endocrinol. Metab.

Euchronism, allochronism, and dyschronism: is internal desynchronization of human circadian rhythms a sign of illness?

Review article
Association between light at night, melatonin secretion, sleep deprivation, and the internal clock: Health impacts and mechanisms of circadian disruption