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Optimal schedules of light exposure for rapidly correcting circadian misalignment.

ABSTRACT: Jet lag arises from a misalignment of circadian biological timing with the timing of human activity, and is caused by rapid transmeridian travel. Jet lag's symptoms, such as depressed cognitive alertness, also arise from work and social schedules misaligned with the timing of the circadian clock. Using experimentally validated mathematical models, we develop a new methodology to find mathematically optimal schedules of light exposure and avoidance for rapidly re-entraining the human circadian system. In simulations, our schedules are found to significantly outperform other recently proposed schedules. Moreover, our schedules appear to be significantly more robust to both noise in light and to inter-individual variations in endogenous circadian period than other proposed schedules. By comparing the optimal schedules for thousands of different situations, and by using general mathematical arguments, we are also able to translate our findings into general principles of optimal circadian re-entrainment. These principles include: 1) a class of schedules where circadian amplitude is only slightly perturbed, optimal for dim light and for small shifts 2) another class of schedules where shifting occurs along the shortest path in phase-space, optimal for bright light and for large shifts 3) the determination that short light pulses are less effective than sustained light if the goal is to re-entrain quickly, and 4) the determination that length of daytime should be significantly shorter when delaying the clock than when advancing it.

SUBMITTER: Serkh K

PROVIDER: S-EPMC3983044 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Optimal schedules of light exposure for rapidly correcting circadian misalignment.

Serkh Kirill K Forger Daniel B DB

PLoS computational biology 20140410 4

Jet lag arises from a misalignment of circadian biological timing with the timing of human activity, and is caused by rapid transmeridian travel. Jet lag's symptoms, such as depressed cognitive alertness, also arise from work and social schedules misaligned with the timing of the circadian clock. Using experimentally validated mathematical models, we develop a new methodology to find mathematically optimal schedules of light exposure and avoidance for rapidly re-entraining the human circadian sy ...[more]

PMID: 24722195

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Project description:BackgroundPhysiological circadian rhythms (CRs) are complex processes with 24-hour oscillations that regulate diverse biological functions. Chronic weekly light/dark (LD) shifting (CR disruption; CRD) in mice results in colonic hyperpermeability. However, the mechanisms behind this phenomenon are incompletely understood. One potential innovative in vitro method to study colonic CRs are colon organoids. The goals of this study were to utilize circadian clock gene Per2 luciferase reporter (Per2::Luc) mice to measure the effects of chronic LD shifting on colonic tissue circadian rhythmicity ex vivo and to determine if organoids made from shifted mice colons recapitulate the in vivo phenotype.MethodsNon-shifted (NS) and shifted (S) BL6 Per2::Luc mice were compared after a 22-week experiment. NS mice had a standard 12h light/12h dark LD cycle throughout. S mice alternated 12h LD patterns weekly, with light from 6am-6pm one week followed by shifting light to 6pm-6am the next week for 22 weeks. Mice were tested for intestinal permeability while colon tissue and organoids were examined for CRs of bioluminescence and proteins of barrier function and cell fate.ResultsThere was no absolute difference in NS vs. S 24h circadian period or phase. However, chronic LD shifting caused Per2::Luc S mice colon tissue to exhibit significantly greater variability in both the period and phase of Per2::Luc rhythms than NS mice colon tissue and organoids. Chronic LD shifting also resulted in increased colonic permeability of the Per2::Luc mice as well as decreased protein markers of intestinal permeability in colonic tissue and organoids from shifted Per2:Luc mice.ConclusionsOur studies support a model in which chronic central circadian disruption by LD shifting alters the circadian phenotype of the colon tissue and results in colon leakiness and loss of colonic barrier function. These CRD-related changes are stably expressed in colon stem cell derived organoids from CRD mice.

Project description:BackgroundCircadian system contributes to the regulation of inflammatory processes, but the role of circadian misalignment as a risk factor for contracting Covid-19 has up to now been poorly studied. The aim of this study was to explore the relationship between circadian misalignment (chronic disturbance of the circadian system) and the risk of Covid-19 infection in a population of subjects suspected of contact or infection with SARS-CoV-2.MethodsCross-sectional single-center study conducted during a period without lockdown in winter 2021. Recruitment took place in a Covid-19 outpatient testing center. Subjects between 18 and 45 years old were included whether they were symptomatic or not, healthcare workers or not, in contact with a Covid-19 case or not. To determine social jetlag, a proxy of circadian misalignment, they were asked about their usual sleep-wake behaviors. Usual sleep duration and sleep-wake timing were explored on workdays and free days. Social jetlag was defined as at least 2 h shift of circadian alignment (defined as the difference between mid-sleep on workdays and mid-sleep on free days, mid-sleep as the median between bedtime and rise time).ResultsOne thousand fourteen subjects were included (sampling rate: 10.8%, 39% men, mean age 28 ± 8) with 56 subjects positive for Covid-19 (positivity rate: 5.5%). Usual mean sleep duration was equivalent in both groups (7h47 versus 7h49, p = 0.733). Social jetlag greater than 2 h comprised 33.3% of subjects in the Covid-19 group versus 20.6% in the control group (p = 0.026). After adjustment on age, gender, BMI and work schedules, subjects presenting with social jetlag greater than 2 h had a 2.07-fold higher likelihood to test positive than subjects who had identical sleep-wake timing on workdays and free days (OR = 2.07, 95%CI = [1.12-3.80], p = 0.024).ConclusionCircadian misalignment not only is present in subjects infected by Covid-19 but could also be responsible for a higher likelihood of being infected. The chronobiological impact on the immune system or a higher likelihood of being exposed to social contacts during nocturnal activities could explain our findings, which need to be confirmed in a future large cohort study. Regular sleep-wake timing could ultimately become a target for preventing Covid-19 infection.

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Optimal schedules of light exposure for rapidly correcting circadian misalignment.

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Optimal schedules of light exposure for rapidly correcting circadian misalignment.

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