Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

Abstract

Both obesity and breast cancer are already recognized worldwide as the most common syndromes in our modern society. Currently, there is accumulating evidence from epidemiological and experimental studies suggesting that these syndromes are closely associated with circadian disruption. It has been suggested that melatonin (MLT) and the circadian clock genes both play an important role in the development of these syndromes. However, we still poorly understand the molecular mechanism underlying the association between circadian disruption and the modern health syndromes. One promising candidate is epigenetic modifications of various genes, including clock genes, circadian-related genes, oncogenes, and metabolic genes. DNA methylation is the most prominent epigenetic signaling tool for gene expression regulation induced by environmental exposures, such as artificial light-at-night (ALAN). In this review, we first provide an overview on the molecular feedback loops that generate the circadian regulation and how circadian disruption by ALAN can impose adverse impacts on public health, particularly metabolic disorders and breast cancer development. We then focus on the relation between ALAN-induced circadian disruption and both global DNA methylation and specific loci methylation in relation to obesity and breast cancer morbidities. DNA hypo-methylation and DNA hyper-methylation, are suggested as the most studied epigenetic tools for the activation and silencing of genes that regulate metabolic and monostatic responses. Finally, we discuss the potential clinical and therapeutic roles of MLT suppression and DNA methylation patterns as novel biomarkers for the early detection of metabolic disorders and breast cancer development.

The emergence of melatonin in oncology: Focus on colorectal cancer

“…The relationship between melatonin and disease is apparent in: (a) affecting its endogenous melatonin levels, particularly the inhibition of the secretory nocturnal peak by excessive lighting at dark time in response to ocular signals, the so‐called “light‐at‐night idea” or LAN hypothesis of Stevens; or (b) disrupting its membrane receptor‐mediated signaling and/or receptor‐independent activities. Concomitantly, the link between circadian alterations (eg, rotating shift work or LAN), (epi)genetic changes, metabolic disorders, immune weakening, altered pattern of the human plasma proteome during circadian misalignment, and the aggravation of cancer risk is a highly discussed health issue, which consequently has generated ample epidemiologic and experimental literature . In this sense, recent additional studies have enriched the epidemiological evidence linking shift work and augmented CRC risk.…”

For everything there is a season: biological rhythms in psychiatry

“…4 Several reviews offer a detailed discussion of the networks that link zeitgebers and circadian patterns. 3,[5][6][7] Essentially, in one of the best characterised pathways, signals about light levels from the retina reach the suprachiasmatic nucleus (SCN), a small cluster of cells in the anterior hypothalamus. The SCN synchronises the body with the environmental light-dark cycle.…”

“…3 For instance, the SCN stimulates synthesis and release of melatonin from the pineal gland during the night. 5 The SCN is remarkably sensitive. Single exposures to bright light lasting just 15 seconds and two minutes can alter circadian patterns (median phase shifts of -34.8 and -45.4 minutes respectively) compared with dim ambient light.…”

“…Photosensitive retinal ganglion cells, which transmit signals about ambient light to the SCN, are especially sensitive to these wave lengths. 5,7 Even low levels of light from devices can, for example, delay sleep, reduce melatonin synthesis and impair next day alertness. 7 Not surprisingly, the increased light that is part of modern life generally disrupts sleep -such as delaying onset and shortening duration 7 -and may increase the risk of some psychiatric disorders.…”

“…1 Disrupted circadian patterns seem to be associated with, for instance, lowered alertness and performance, and an increased risk of obesity, cardiovascular, sleep-wake, psychiatric, immunological and metabolic disorders as well as certain cancers. [3][4][5] Indeed, sleep deprivation associated with the transition from day to night shifts can impair performance more than the legal blood alcohol limit. 7 'Social jet lag', for example, refers to the difference between the time that your alarm makes you crawl out of bed and your natural wake time.…”