High sensitivity and interindividual variability in the response of the human circadian system to evening light

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BrianR
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High sensitivity and interindividual variability in the response of the human circadian system to evening light

Post by BrianR »

https://www.pnas.org/content/pnas/early ... 6.full.pdf
Interesting short sleep-related paper demonstrating responses to evening light. Not surprisingly, response varied significantly across the population.

It would be nice to be able to take an inexpensive test to determine personal melatonin response.

High sensitivity and interindividual variability in the response of the human circadian system to evening light
Andrew J. K. Phillipsa, Parisa Vidafara, Angus C. Burnsa, Elise M. McGlashana, Clare Andersona, Shantha M. W. Rajaratnama, Steven W. Lockleya, and Sean W. Caina
doi: 10.1073/pnas.1901824116


Abstract
Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light— stimuli at extreme ends of the circadian system’s dose–response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30–300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting.

We characterized individual-level dose–response curves to light-induced melatonin suppression using a withinsubjects protocol. Fifty-five participants (aged 18–30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10– 2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock’s role in human health and disease.
10.1073-pnas.1901824116 Figure 2.png
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Plumster
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Re: High sensitivity and interindividual variability in the response of the human circadian system to evening light

Post by Plumster »

It would be nice to be able to take an inexpensive test to determine personal melatonin response.
Rhonda Patrick's inexpensive "Circadian Report" will let you know if you have the MTNR1A gene, indicating if you are more sensitive to nocturnal light. (I am.)
https://www.foundmyfitness.com/genetics
e3/4 MTHFR C677T/A1298C COMT V158M++ COMT H62H++ MTRR A66G ++ HLA DR
BrianR
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Re: High sensitivity and interindividual variability in the response of the human circadian system to evening light

Post by BrianR »

Interesting, particularly for the AD association. From a FoundMyFitness genetic report done last year (my SNP variant is apparently (C:C)
MTNR1A rs12506228(C;C)
There is a common polymorphism located downstream of melatonin receptor type 1A gene ( MTNR1A) that codes for the MT1 melatonin receptor. Melatonin is a hormone produced primarily by the pineal gland in the brain. Melatonin, which is secreted in high levels at night, decreases with age and is particularly low in Alzheimer’s disease (AD) patients. Along with dementia, sleep disturbances and altered circadian rhythms are commonly observed in AD patients.

This genotype, rs12506228(C;C) is associated with normal risk for late-onset Alzheimer’s disease (AD).
However, those with the A allele may have an increased risk for late-onset AD. In a study of 512 Finnish individuals, aged 85+ years, subjects were assessed for AD and followed for 10 years. The A allele was significantly associated with clinical signs of AD, such as dementia. When brain tissue was examined post- mortem, A allele carriers had more amyloid-beta plaques and neurofibrillary tangles (hallmark signs of AD) than those without the A allele. In fact, all (A;A) subjects had severe amyloid-beta plaques and neurofibrillary tangles upon autopsy. This association was confirmed in a second case-control cohort of 673 AD patients and 686 controls (participants over age 75). This association was not observed in a case-control study of younger individuals (average age 70).

SNPs Involved
rs12506228(C;C)
Plumster
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Re: High sensitivity and interindividual variability in the response of the human circadian system to evening light

Post by Plumster »

Good for you, Brian! Here's mine, (C, A), and less fortunate:
Slight increased risk for late- onset alzheimer’s disease

More information
There is a common polymorphism located downstream of melatonin receptor type 1A gene ( MTNR1A) that codes for the MT1 melatonin receptor. Melatonin is a hormone produced primarily by the pineal gland in the brain. Melatonin, which is secreted in high levels at night, decreases with age and is particularly low in Alzheimer’s disease (AD) patients. Along with dementia, sleep disturbances and altered circadian rhythms are commonly observed in AD patients.

This genotype, rs12506228(A;C) is associated with a slight increased risk for late-onset Alzheimer’s disease (AD).
512 Finnish individuals, aged 85+ years, were assessed for AD and followed for 10 years . The A allele was significantly associated with clinical signs of AD, such as dementia. When brain tissue was examined post- mortem, A allele carriers had more amyloid-beta plaques and neurofibrillary tangles (hallmark signs of AD) than those without the A allele. In fact, all (A;A) subjects had severe amyloid-beta plaques and neurofibrillary tangles upon autopsy. This association was confirmed in a second case-control cohort of 673 AD patients and 686 controls (participants over age 75). This association was not observed in a case-control study of younger individuals (average age 70).
In vitro experiments in mouse cell lines containing the human MTNR1A gene, when either silenced or overexpressed, showed that decreasing MT1 receptors led to increased amyloidogenic proteins, while increasing MT1 receptors decreased this effect.

A genome wide association study in Finnish shift workers, found that this polymorphism was associated with an intolerance to shift work. Individuals with the A allele experienced more symptoms such as persistent fatigue than non A allele carriers when exposed to shift work. The A allele was associated with reduced MTNR1A gene expression, and therefore, fewer melatonin receptors in the brain. The authors suggest that carriers of the A allele may be more sensitive to nocturnal light than non-carriers.

These studies would suggest that a lifestyle that does not disrupt the circadian rhythm would be beneficial to individuals with this polymorphism. Furthermore, since individuals with this genotype may have fewer
melatonin receptors thus increasing sensitivity to nighttime light, avoiding blue light 3-5 hours before bedtime may help improve sleep latency and quality. Sleep has been shown in a mouse model , to promote the clearing of amyloid-beta peptides from the brain via glymphatic system activation. Whereas lack of sleep for just one night boosted levels of amyloid beta (biomarker linked to Alzheimer's) by 25-30% in humans.
e3/4 MTHFR C677T/A1298C COMT V158M++ COMT H62H++ MTRR A66G ++ HLA DR
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