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Relógio circadiano durante um vôo


Estou interessado em saber como nosso relógio circadiano responde (e se há mudanças resultantes) quando viajamos através de fusos horários.

ATUALIZAÇÃO 24 de abril

Estou reabrindo esta questão como a declaração na resposta "Quando você viaja para fusos horários diferentes, seu relógio circadiano estará desligado"me confundiu ainda mais. Se for o caso, então procuro obter uma explicação melhor do que essa (com referências sólidas) Obrigado


Quando você viaja para fusos horários diferentes, o relógio circadiano fica desligado (incorreto). O motivo pelo qual seu relógio circadiano estará desligado é porque seu corpo se adaptou ao fuso horário de onde você está. Quando você entra em um novo fuso horário, seu relógio circadiano ainda estará funcionando no antigo fuso horário. Se a diferença de fuso horário for $ pm 12 $ horas, este é um grande ajuste.

No entanto, seu corpo recebe informações do meio ambiente. Ou seja, você pode ver que é luz do dia quando seu corpo tem a impressão de que é noite. O relógio circadiano é controlado pelo relógio principal localizado no hipotálamo. Conforme você recebe essas entradas externas que contrariam seu relógio circadiano, um grupo de células nervosas chamado núcleo supraquiasmágico fará lentamente o ajuste do relógio mestre [1]. Essa redefinição pode levar alguns dias.

Além disso, tem havido um pouco de pesquisa sobre exercícios para reduzir o jet lag. Em um estudo, pesquisadores testaram exercícios ao ar livre com membros da tripulação de vôo e descobriram que o grupo que se exercitou ao ar livre teve uma re-sincronização apressada de seu relógio circadiano [2].

Outro artigo interessante é Jet Lag em Atletas.


Cronobiologia

Cronobiologia é um campo da biologia que examina os processos de tempo, incluindo fenômenos periódicos (cíclicos) em organismos vivos, como sua adaptação aos ritmos relacionados ao sol e à lua. [1] Esses ciclos são conhecidos como ritmos biológicos. Cronobiologia vem do grego antigo χρόνος (chrónos, que significa "tempo") e biologia, que pertence ao estudo ou ciência da vida. Os termos relacionados cronômica e cronomo têm sido usados ​​em alguns casos para descrever os mecanismos moleculares envolvidos nos fenômenos cronobiológicos ou os aspectos mais quantitativos da cronobiologia, particularmente quando a comparação de ciclos entre organismos é necessária.

Os estudos cronobiológicos incluem, mas não estão limitados a, anatomia comparativa, fisiologia, genética, biologia molecular e comportamento de organismos relacionados a seus ritmos biológicos. [1] Outros aspectos incluem epigenética, desenvolvimento, reprodução, ecologia e evolução.


Relógio circadiano e sono

O relógio circadiano controla quase todos os padrões da biologia humana, incluindo atividade das ondas cerebrais, ciclos de sono-vigília, temperatura corporal, secreção de hormônios, pressão sanguínea, regeneração celular, metabolismo e comportamento, que exibem

Periodicidade de 24 horas [3]. Além disso, cognição e desempenho também estão sob controle circadiano [4].

Em mamíferos e humanos, o relógio circadiano consiste em um relógio central e relógios de tecido periférico. O relógio central está localizado nos núcleos supraquiasmáticos (SCN) do hipotálamo, que funciona como o marca-passo mestre, sincronizando ritmos fisiológicos de acordo com o ambiente de ciclismo da Terra. O relógio central opera para sincronizar os relógios nos tecidos periféricos [3, 5].

No nível molecular, os relógios dos mamíferos são compostos de elementos positivos e negativos que impulsionam a ritmicidade da expressão gênica. BMAL1 e CLOCK são dois elementos positivos que se ligam aos promotores do Período (Per1 e Per2) genes e Criptocromo (Cry1 e Cry2) genes e facilitam sua transcrição. Os produtos proteicos PER e CRY se acumulam, dimerizam e atuam como elementos negativos que se ligam a elementos positivos, o que leva à repressão de sua própria transcrição. Esses circuitos positivos e negativos formam um loop de feedback negativo que é essencial para os relógios circadianos eucarióticos [5].

O período de funcionamento livre do relógio humano é ligeiramente mais longo do que 24 horas, mas é arrastado para 24 horas pela sincronização com os fatores ambientais do ciclo diário. Esses fatores, como luz e temperatura, agem como zeitgebers (pistas externas que dão tempo) que definem a fase dos ritmos circadianos [6–8]. Entre os zeitgebers, a luz é a principal entrada para o relógio central, que coordena a fisiologia interna com o ambiente externo para otimizar a sobrevivência [9]. A luz brilhante & gt2.500 lux é suficiente para sincronizar o relógio circadiano humano, e a luz é freqüentemente usada no tratamento de distúrbios associados à dessincronização circadiana [10].

O sono é um grande componente do ciclo circadiano diário e é regulado cooperativamente por fatores homeostáticos e circadianos. O despertar normal está associado à atividade neuronal em vários sistemas de despertar ascendentes quimicamente definidos [11]. Os sistemas de excitação ascendente incluem neurônios monoaminérgicos no tronco encefálico e hipotálamo posterior, neurônios colinérgicos no tronco encefálico e prosencéfalo basal e neurônios orexina no hipotálamo lateral. Um importante conjunto de neurônios relacionados ao sono está localizado no hipotálamo pré-óptico, incluindo a área pré-óptica ventrolateral (VLPO) e o núcleo pré-óptico mediano [11].

Os neurônios em cada um dos núcleos monoaminérgicos disparam mais rapidamente durante a vigília do que durante o sono. Os disparos diminuem significativamente durante o sono de movimentos oculares não rápidos (não REM ou NREM) e param totalmente durante o sono REM [5, 12, 13]. Os neurônios de Orexin são similarmente mais ativos durante a vigília do que durante o sono [14]. Muitos neurônios basais do prosencéfalo, incluindo a maioria dos neurônios colinérgicos, estão ativos durante a vigília e o sono REM [5]. Os neurônios VLPO são principalmente ativos durante o sono e contêm os neurotransmissores inibitórios galanina e GABA [15, 16]. A área VLPO inibe as regiões de excitação ascendente e, por sua vez, é inibida por elas, formando assim um sistema mutuamente inibitório semelhante ao que os engenheiros elétricos chamam de “interruptor flip-flop” [17, 18].

A propensão circadiana para o sono aumenta durante o estado de sono, garantindo assim a continuidade do sono, apesar da diminuição da necessidade homeostática dele no final do ciclo do sono. Evidências anatômicas e funcionais indicam que existe uma relação entre o SCN e o sistema sono-vigília. O SCN tem projeções relativamente modestas nos neurônios VLPO e orexina [19-21]. No entanto, o principal débito é direcionado para a zona subparaventricular adjacente e o núcleo dorsomedial do hipotálamo. Lesões específicas de células na zona subparaventricular ventral ou no núcleo dorsomedial do hipotálamo perturbam os ritmos circadianos do sono e da vigília, sugerindo que os neurônios nessas áreas devem transmitir essa influência [22, 23]. A interrupção do tempo de sono-vigília pode levar ao desalinhamento da ritmicidade nas variáveis ​​fisiológicas. A privação do sono causa deterioração e diminuição do desempenho [24]. O sono insuficiente ou mal cronometrado pode reduzir a ritmicidade dos genes controlados pelo relógio [6, 25]. Esses fatos sugerem que o relógio circadiano e o sono se regulam mutuamente nos níveis molecular e fisiológico (Figura 1).

Diagrama de rede do relógio circadiano, sono, fisiologia e comportamento no espaço. No espaço, uma variedade de fatores ambientais estão envolvidos na regulação do relógio circadiano e do sono. O relógio circadiano e o sono se regulam mutuamente. O alinhamento do relógio circadiano e do sono é crítico para a fisiologia, comportamento e desempenho. Por sua vez, o comportamento e o desempenho podem afetar o relógio circadiano e o sono.


O Prêmio Nobel de Medicina vai para o seu corpo & relógio circadiano # 39

Para revisar este artigo, visite Meu perfil e, em seguida, Exibir histórias salvas.

Professor Michael Rosbash, um dos ganhadores do Prêmio Nobel de Medicina. Scott Eisen / Getty Images

Para revisar este artigo, visite Meu perfil e, em seguida, Exibir histórias salvas.

Hoje, o comitê do Nobel deu início à temporada de 2017 ao conceder o Prêmio Nobel de Fisiologia ou Medicina a três cientistas por suas descobertas dos mecanismos moleculares que controlam os ritmos circadianos. Os americanos - Jeffrey C. Hall, Michael Rosbash e Michael W. Young - usaram as moscas da fruta para isolar um gene que dita o tique-taque do relógio biológico dentro de todos os organismos vivos. Seu trabalho, embora tenha décadas, foi crucial para entender como a luz que emana das telas pode afetar o bem-estar dos humanos, pois leva as pessoas cada vez mais fora de sincronia com seus cronometristas internos.

A ciência mais recente e mais brilhante dominou as previsões no anúncio de segunda-feira. Crispr, o sistema de edição de genes transformacional sendo aproveitado para fazer safras resistentes ao clima, biocombustíveis mais abundantes e terapias de ponta, foi abandonado este ano. Assim como o trabalho pioneiro no campo promissor da imuno-oncologia, em que o sistema imunológico do corpo é iniciado para lutar contra o câncer sem a necessidade de quimioterapia tóxica ou radiação.

No final, o comitê do Prêmio Nobel reconheceu o trabalho menos moderno, mas cada vez mais relevante de Hall, Rosbash e Young por explicar algo tão fundamental como “como as plantas, animais e humanos adaptam seu ritmo biológico para que seja sincronizado com o da Terra revoluções. ”

Isso mesmo: os ciclos lunares não são apenas para astrólogos e espiritualistas portadores de cristais. Todos os organismos operam em um circuito de 24 horas que governa funções críticas, como pressão sanguínea, frequência cardíaca, temperatura corporal, níveis hormonais, metabolismo, sono e até comportamento - tudo no tempo com mudanças entre dia e noite. Mas foi só em 1984 que Hall, Rosbash e Young identificaram um gene que parecia controlar esse ritmo circadiano. Trabalhando com moscas da fruta, eles descobriram que os insetos sem esse gene também perdiam a capacidade de autorregular essas funções biológicas. Substituir a função do gene deu a eles seu sulco de volta.


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Envelhecimento: religando o relógio circadiano

A robustez do relógio circadiano se deteriora com o envelhecimento. Dois novos estudos mostram que o envelhecimento reprograma o transcriptoma circadiano de uma maneira dependente do tipo de célula e que essa reconfiguração pode ser revertida pela restrição calórica.

O assunto da restrição calórica (CR) é de amplo interesse porque é a intervenção mais robusta para estender a vida útil dos mamíferos. Mais impressionante, reverte o declínio fisiológico associado ao envelhecimento e melhora um amplo espectro de doenças 1,2. Acreditava-se que esse regime alimentar traz benefícios à saúde por meio de um efeito passivo de redução da taxa metabólica. No entanto, avanços recentes na pesquisa do envelhecimento favorecem a visão de que os efeitos orgânicos da RC em mamíferos são processos ativamente regulados 3,4. Dois estudos recentes de Sato et al. 5 e Solanas et al. 6 revelam que o envelhecimento reprograma o transcriptoma circadiano de uma maneira dependente do tipo de célula e que essa reconfiguração pode ser revertida pela administração da dieta RC. Esses achados fornecem 'impressões digitais' moleculares de alta resolução da resposta circadiana ao envelhecimento fisiológico e RC e adicionam novas evidências para o conceito emergente de que as condições associadas ao envelhecimento podem ser revertidas 7,8,9.


Hackeando o relógio biológico

Os antigos egípcios usavam relógios de água para medir a passagem do tempo. Os relógios mecânicos começaram a bater na Europa do século 14 e os relógios de bolso, no século 17. A Timex foi fundada em 1854 e a Rolex em 1905. Hoje, você pode usar um smartphone para acompanhar sua programação. Mas antes de todos esses cronômetros, havia células vivas - eles próprios cronometristas impecáveis.

As células do corpo humano seguem ciclos que se repetem em qualquer lugar de uma vez por segundo, no caso de um batimento cardíaco, a uma vez por mês, para o ciclo reprodutivo feminino. Os organismos vivos têm ciclos biológicos que abrangem todos os tipos de intervalos de tempo - as células bacterianas de replicação mais rápida duplicam a cada 15 minutos, os ursos hibernam anualmente, algumas espécies de cigarras emergem do solo apenas uma vez a cada 17 anos e muitas plantas de bambu duram mais de 60 anos sem floração.

Os cientistas observaram esses ciclos com admiração, perguntando o que mantém esses relógios funcionando. Lentamente, eles revelaram muitas das engrenagens moleculares que permitem que as células se mantenham dentro do cronograma. E mesmo entre espécies díspares - e entre ciclos com períodos drasticamente diferentes - eles descobriram semelhanças.

“Todos esses ciclos são movidos por relógios”, diz James Ferrell, MD, PhD, professor de Stanford de química e biologia de sistemas e de bioquímica. “Não há quase nada em comum entre cada relógio quando se trata dos genes e proteínas exatos envolvidos. Mas em um nível fundamental, cada tipo de circuito é o mesmo. ”

Com esse conhecimento em mente, os cientistas agora se voltaram para um novo tipo de questão: como podemos tirar proveito do que sabemos sobre o relógio? Alguns pesquisadores estão explorando como combater o jet lag ou tratar a narcolepsia e a insônia, alterando os ciclos do sono. Alguns estão investigando como administrar diferentes medicamentos - de vacinas a drogas que aumentam a memória - administrando-os na hora do dia em que são mais eficazes. E outros estão trabalhando para impedir o crescimento do tumor, desacelerando o relógio que controla a velocidade com que as células cancerosas se dividem. Em Stanford e em fusos horários ao redor do mundo, os cientistas estão aprendendo não apenas como desmontar um relógio e ver seu interior, mas como remontá-lo da maneira que quiserem, evitando que fique desequilibrado ou colocando-o de volta nos trilhos quando perdeu a noção do tempo.

Maquinário básico

Assim como os mesmos princípios básicos dos circuitos eletrônicos são usados ​​para projetar máquinas, de calculadoras e rádios a carros e telefones celulares, todos os relógios biológicos são governados pelos mesmos padrões básicos de interruptores moleculares. Mas, ao contrário dos circuitos eletrônicos compostos de fios, metais e silício, os circuitos celulares são feitos de moléculas que funcionam juntas em um grande jogo de etiqueta, ligando e desligando umas às outras.

Para entender os circuitos moleculares que sustentam os relógios biológicos, Ferrell estuda um dos temporizadores mais integrais da vida: o ciclo celular. Todas as células vivas na Terra - de bactérias a células-tronco - passam por um ciclo celular semelhante, que inclui crescer, copiar o material genético, dividi-lo e formar duas novas células. O ciclo celular é como um embrião se desenvolve, como as células da pele são constantemente substituídas e por que você não consegue fazer seu cabelo e unhas pararem de crescer.

“You can think of the cell cycle as being driven by a clock in the same way you think of heart rate or sleep patterns being driven by clocks,” says Ferrell.

Human cells go through a cell cycle every 24 hours on average. But many organisms have faster cell cycles: Yeast cells divide every few hours, frog embryos cycle every 25 minutes and bacteria multiply even faster.

Recently, researchers started hypothesizing how sets of molecules might control this timing. One idea, says Ferrell, was that it’s driven by a positive feedback cycle. That would mean that a set of molecules switch each other on in brief pulses, like people passing a hand squeeze around in a circle. If it took a fixed amount of time for the signal to get back to the start of the circle, then a clock — or, in more technical terms, an oscillator — would be born. Every time the signal would hit one molecule in the cycle, it could spur some other biological process, be it cell division or hunger for lunch.

But when Ferrell and others started running computer simulations on how a positive molecular feedback loop could keep a biological clock ticking, their results didn’t click. “It makes complete sense that positive feedback should be able to work as an oscillator,” says Ferrell. “But it just doesn’t work. It turns out that the circuit will either eventually fade out to nothing, or end up with everything turned on all the time. The balancing point between these is just too fine a knife blade.”

Instead, biological clocks seem to always be driven by a negative feedback loop. In retrospect, Ferrell says, although it wasn’t the intuitive answer, this fits with what modeling and theories have been suggesting for a few decades in fact, mathematician René Thomas conjectured in 1981 that all complex oscillators must contain a negative feedback loop.

Ferrell’s lab has spent the past few decades studying the negative feedback loop that controls the cell cycle. Like a positive feedback loop, a negative feedback loop involves molecules passing a signal in a circle. But in this case, they don’t just turn each other on in pulses: They alternately turn each other on and off. The cell cycle, though, isn’t just a simple loop — it also has all sorts of checkpoints. These ensure, for instance, that a cell doesn’t start copying its genetic material if it hasn’t grown large enough.

But the cell cycle — like many other biological clocks — can be complicated by the fact that it sometimes speeds up or slows down. In some cases, this is OK cells in frog embryos, for instance, begin dividing slowly and speed up as they grow larger. But in other cases, this can lead to disease: Cells that progress through many fast cell cycles in a row can form a cancerous tumor. So, understanding how cells control the pace of the cell cycle is key to understanding one of the most fundamental properties of cancer.

“Every cell type in the body does the cycle a little bit differently they’re very idiosyncratic,” Ferrell says. “And even within one population of cells, the cycle can speed up and slow down.” And then there are cancer cells: the fastest dividing cells of them all. Cancers cells march through the cell cycle at a faster pace than other cells, and that’s what makes tumors grow so aggressively. “The hope is that if we understand the cell cycle better, we can design more effective therapies for cancer,” he says.

Ferrell’s group has turned to frog embryos, because of their unusually reliable cell cycle length, to learn in more detail what proteins and genes control the speed of this clock. Using frog eggs, he’s shown why the first division cycle of the embryo is long, about 80 minutes, while those following are less than half an hour. The difference, he found, is due to the ratio of two proteins: Having more of one protein leads to the longer cycle. The lesson isn’t directly applicable to cancer cells — tumors don’t contain those same two proteins — but gives scientists hints about how cancer cell cycles might be sped up. Already, researchers have found that many tumor suppressor genes and oncogenes are directly involved in cell cycle checkpoints. Drugs targeting these pathways — and therefore restoring the cell cycle to its normal pace — are in clinical trials.

Sleep’s concert conductor

As cells tick tock through the cell cycle, other rhythms in the human body are progressing at their own paces. For anyone who has ever flown halfway around the globe only to spend days like a zombie and nights wide awake, the steady beat of one clock is obvious: the sleep cycle. Most of us find our bodies sticking to a 24-hour pattern of sleep we get drowsy around the same time each night.

At the Stanford Center for Narcolepsy, sleep doctor and researcher Emmanuel Mignot, MD, PhD, is using findings he’s made on the human sleep cycle over the past few decades to develop new treatments for sleep disorders, including narcolepsy. Patients with narcolepsy have severe disturbances in their sleep-wake cycles, often characterized by sudden bouts of extreme fatigue during the day. At the end of the 1990s, Mignot and his colleagues identified the first narcolepsy gene, hypocretin receptor 2, in dogs. Since then, they’ve uncovered how a lack of the protein hypocretin in mammals, including humans, can cause narcolepsy. In most people, hypocretin levels peak during the day, when the protein promotes wakefulness and blocks sleep, Mignot has shown. In many people with narcolepsy, hypocretin is missing — or is found at very low levels in the brain — so the sleep pathways aren’t blocked during the day.

But even uncovering hypocretin hasn’t answered some of the most basic questions on why most of us have a regular pattern of alertness and fatigue and what other molecules wax and wane in tune with the sleep cycle. “The hypocretin system is like an orchestra director,” Mignot says. “It’s controlling the music — sleep and wake — but not making it. Right now we don’t even know who’s in the orchestra or what music is being played during sleep or wake.”

There’s another interesting cycle linked to narcolepsy, though, that’s leading to unexpected findings — an annual cycle. “There are always a lot more new cases of narcolepsy during the spring and summer,” Mignot explains. “And there was a huge rise in the number of narcolepsy cases in 2010 just after the winter of the swine flu.”

Mignot’s latest research looks at this intersection between this seasonal cycle and the sleep cycle. The onset of narcolepsy, he’s shown, can likely be triggered by a case of the flu, which may be asymptomatic and tends to happen over the winter. A few months later, narcolepsy appears. Mignot has been among the scientists who have shown over the past decade that most narcoleptics have an overactive immune system that attacks the cells that produce hypocretin, causing the lack of hypocretins. This problem, he thinks, may be triggered by the body’s production of immune cells produced to fight specific strains of influenza.

“It’s turning out to be quite an interesting journey looking at this,” says Mignot.

Through this research, Mignot is illuminating not only ways to treat narcolepsy, but other sleep disorders, like insomnia an insomnia drug related to the hypocretin system is hitting the market soon.

“The view now is that healthy sleep is as important as diet or exercise to overall health,” Mignot says. “And sleep disorders of any kind are really an important societal problem.”

Cycles of learning

If anyone knows how surprisingly different the body can be at different points in its rhythmic cycles, it’s biologist Craig Heller, PhD, who co-directs the Stanford Down Syndrome Research Center. Mice with the genetic mutation that causes Down syndrome in people usually have trouble learning and on memory tests. They quickly forget objects they’ve seen and can’t remember how to complete a maze. But when Heller gives these mice a dose of pentylenetetrazole each day as the sun rises, before these nocturnal animals go to sleep, he can reverse their deficits. For months after receiving a two-week morning regimen of PTZ, the mice score better on memory tests. When Heller switches the timing of the daily PTZ dose, though, giving the drug at night instead of during the day, suddenly its effects completely disappear.

“This is becoming more and more appreciated in medicine,” says Heller. “The body is not the same at all hours of the day, and some drugs should be given at particular times to be most effective.”

The brain, it turns out, goes through daily cycles of learning and memory storage, coinciding with when a mouse (or a person) sleeps. So at different times of day, PTZ interacts differently with the brain.

When Heller made the observation that his Down syndrome treatment wasn’t as effective at night, when mice are active, as it was during the day, when mice are asleep, he began trying to make a link between circadian rhythms and sleep cycles and learning and memory. The crux of his research rests on the basic idea that the brain has two opposing functions: turning on neurons so they can communicate, and — at other times — blocking neurons from communicating. While people are sleeping, Heller has shown, this mandatory quiet time in the brain is especially vital. When the circadian rhythms of hamsters are obliterated, the animals no longer remember things from day to day.

“You’d think that inhibiting brain activity would always be contrary to our ability to learn and remember,” Heller says. “But while a person or animal is sleeping, memories from their daily experience are being translated into long-term memories, and as these memories are being moved from one part of the brain to another, they’re vulnerable to being altered.” During that process, he says, it’s important for most of the brain to not have any new activity, which could change the memory. PTZ, though, helps ensure that the activity ban isn’t too harsh some areas of the brain need to function to store the memory. Having shown that PTZ treatment before sleep can lead to memory improvements in mice with Down syndrome and in hamsters lacking circadian rhythms, Heller is investigating whether the drug can treat other neurological conditions as well.

To further understand the role of this daily activity cycle in the brain, Heller’s group has studied what happens when memories are, incorrectly, reactivated during sleep. He trained mice to associate a particular smell with a shock. Then, during the day while the mice were sleeping, he piped the odor back into some of their cages. The mice who had re-experienced the smell had a much stronger fear response to the smell the next day. And, on the flip side, when the scientists blocked the whole brain from making new connections during the night, the mice didn’t remember the smell at all the next day.

Resetting the body’s clock

In collaboration with Jamie Zeitzer, PhD, associate professor of psychiatry and behavioral sciences at the medical school and at the Veterans Affairs Palo Alto Health Care System, Heller has also been studying more basic questions about circadian rhythms in people — and how to change these rhythms. The easiest way to alter the circadian clock, scientists know, is by exposing someone to light during their normal sleeping hours. This more quickly shifts the body’s clock than exposure to darkness during the waking hours.

“Typically, researchers thought someone had to be exposed to at least half an hour of constant light to shift the clock,” says Heller.

But if you’re on a plane with the lights out, working nights or arrive in a new time zone after the sun has set, it might not be possible to get this half-hour of light to get your clock on the right schedule. So Heller and Zeitzer started investigating whether shorter bursts of light could do the trick. In both human and mouse studies, they’ve now shown that 2 millisecond flashes of light every 30 seconds for an hour during the night — while it doesn’t interrupt sleep — can make people wake up earlier in the morning, shifting their circadian clock by almost an hour. The finding could lead to the development of new devices to help people avoid jet lag or adjust to a new shift at work.

“You could build these timed light pulses into glasses or travel alarm clocks or the cabins of airplanes to prevent jet lag,” says Heller. By exposing someone to a series of flashes during a flight, for instance, Heller thinks he could shift their clock enough to at least ease the transition to a new time zone, although the flashes of light wouldn’t help you sleep in if you’re traveling in the other direction.

For world travelers, preventing jet lag might be the ultimate biological clock hack. But even if you don’t jet around the globe on a regular basis, the ways scientists are learning to take advantage of your body’s cycles could help you recover faster from an illness, sleep more effectively, adjust to a new schedule or get better at learning new things. And as researchers continue to learn more about how cycles drive the rhythm of life, they’ll surely realize new ways to use this information.


Circadian Rhythm: Resetting the Biological Clock by Flipping a Switch

Reversible modulation of the circadian clock using chronophotopharmacology. Using light to interconvert two isomers of a photo-responsive small molecule, it is possible to pace cellular time. While irradiation with violet light extends the normal 24-hour clock to 28-hour, green light switches off this effect and brings the clock back to normal. Credit: Issey Takahashi

The biological clock is present in almost all cells of an organism. As more and more evidence emerges that clocks in certain organs could be out of sync, there is a need to investigate and reset these clocks locally. Scientists from the Netherlands and Japan introduced a light-controlled on/off switch to a kinase inhibitor, which affects clock function. This gives them control of the biological clock in cultured cells and explanted tissue. They publish their results today (May 26, 2021) in Nature Communications.

Life on Earth has evolved under a 24-hour cycle of light and dark, hot and cold. “As a result, our cells are synchronized to these 24-hour oscillations,” says Wiktor Szymanski, Professor of Radiological Chemistry at the University Medical Center Groningen. Our circadian clock is regulated by a central controller in the suprachiasmatic nucleus, a region in the brain directly above the optic nerve, but all our cells contain a clock of their own. These clocks consist of an oscillation in the production and breakdown of certain proteins.

Light switch

“It is becoming increasingly clear that these clocks can be disrupted in organs or tissues, which may lead to disease,” adds first author Dušan Kolarski, a PhD student from the group led by Ben Feringa, Professor of Organic Chemistry. And, of course, we all know about jet lag, which is caused by travel across time zones, or problems that are caused by the switch to or from daylight saving time. “We know very little about how our cells coordinate these oscillations, or how it affects the body if, for example, one kidney is out of phase with the rest of the body,” he adds.

This picture shows first author Dusan Kolarski (back row, left) with the team from the Institute of Transformative Bio-Molecules at Nagoya University, Japan, including co-authors Tsuyoshi Hirota (back row, middle), Akiko Sugiyama (front, second from left) and Yoshiko Nagai (front, fourth from left). Credit: Institute of Transformative Bio-Molecules, Nagoya University

To study these effects, it would be useful to have a drug that affects the clocks and that can be activated locally. The latter is something that the groups of Szymanski and Feringa have done before. They created several compounds, such as antibiotics or anticancer drugs, that could be switched on and off with light. Previously, circadian biologist Tsuyoshi Hirota, associate professor at the Institute of Transformative Bio-Molecules at Nagoya University, Japan, developed a kinase inhibitor, longdaysin, which slows down the circadian clock to a cycle that lasts up to 48 hours. Kolarski fitted this longdaysin with a light switch that allowed him to activate or deactivate the compound with violet and green light, respectively.

Time zone

Developing this adaptation took Kolarski several years, but the result was well worth the effort. “It was a real scientific ‘Tour de Force’ and a beautiful example of interdisciplinary cooperation,” adds Feringa. Together with their Japanese colleagues at Nagoya University, the scientists from the University of Groningen showed how the cycle of cultured cells was extended from 24 to 28 hours by treatment with the longdaysin derivative. Deactivation with green light brought the cycle back to just over 25 hours and subsequent reactivation with violet light returned it to 28 hours.

“We also used it in tissue slices from the mouse suprachiasmatic nucleus,” says Kolarski. “The oscillations slowed to a 26-hour cycle after treatment for several days with the longdaysin derivative and returned to a 24-hour cycle after deactivation with green light.”

“This reversible regulation will provide a new approach to analyzing how the clock in each cell is organized at the tissue level to gain a deeper understanding of the complex circadian clock system,” Hirota adds.

The scientists also adjusted the phase of the cycles in cultured cells: a three-day activation of the longdaysin derivative followed by deactivation caused a shift in the 24-hour cycle by up to six hours. This is as if the cells were synchronized with a different time zone. The experiments are a proof of principle and will allow scientists to study the circadian clock in much more detail. A next step would be to use longdaysin in animals. Kolarski: “The original longdaysin, without the switch, has been used before in zebrafish. We would very much like to test it in mice. The aim is not to fix jet lag but to study the effect of longdaysin on physiology.”

Organs

A light-activated drug such as longdaysin will probably only be used to treat serious conditions. “We can actually reach quite a few organs with light, for example with an endoscope. The gastrointestinal tract and the respiratory system are easily reached, while other tissues may require small incisions to insert optic fibers,” comments Szymanski. There are also several emerging options to generate light inside organs or tissues, through techniques such as bioluminescence or sonoluminescence. Although these levels of light are still several orders of magnitude below what we need to flick a switch. We will work hard to increase sensitivity in the coming years, emphasize both Szymanski and Feringa. Kolarski adds: “We have now opened a new field of study. Eventually, all this will allow us to locally disrupt or repair the circadian oscillations.”

Simple Science Summary

The cells in our body follow a 24-hour cycle, the circadian clock. Disruptions of this cycle, for example by working night shifts, can cause disease. In recent years, it has become clear that the clock can be disrupted in individual organs or tissues. To study and potentially cure problems with the clocks inside our cells, Dutch and Japanese scientists created a compound that will elongate the 24-hour cycle and that can be activated or deactivated using light. They showed that it is possible to change the 24-hour cycle in cells or tissues to a 28-hour cycle by activating the compound. After deactivation, the cells and tissues returned to a near-normal cycle. The compound can be used to investigate the clocks inside our cells and may eventually be used to treat diseases that are caused by a disrupted clock.

Reference: “Reversible modulation of circadian time with chronophotopharmacology” by Reference: Dušan Kolarski, Carla Miró Vinyals, Akiko Sugiyama, Ashutosh Srivastava, Daisuke Ono, Yoshiko Nagai, Mui Iida, Kenichiro Itami, Florence Tama, Wiktor Szymanski, Tsuyoshi Hirota and Ben L. Feringa, 26 May 2021, Nature Communications.
DOI: 10.1038/s41467-021-23301-x


Circadian Physiology Program

The Circadian Physiology Program focuses on basic and applied aspects of human circadian biology. Our translational approach includes use of a range of techniques including epidemiology, field-based physiological studies and inpatient intensive physiological monitoring.

We have a particular interest in human circadian photoreception and the effects of light on the circadian pacemaker and other non-image forming responses. Our studies include investigations of the effects of timing, duration, intensity and wavelength of light exposure on circadian resetting, melatonin suppression and the acute alerting effects of light. We are also conducting a series of applied lighting interventions to improve circadian rhythms, sleep and performance on the International Space Station and other NASA analogs, care homes, hospitals, and offices. This work is also being translated into architectural lighting design approaches and lighting standards.

We have studied visually impaired individuals under field and laboratory conditions to examine the effects of the severity and type of blindness on circadian photoreception, the periodicity of the circadian pacemaker and development of circadian rhythm sleep disorders, which led to the development of novel therapeutic strategies to treat non-24-hour sleep wake disorder in the blind, as well as other health risks such as breast cancer.

We have also conducted field and laboratory studies to assess the wider impact of circadian rhythms on a range of physiological systems including immune response, bone metabolism, reproductive function, liver function and lipid and glucose regulation, and are examining these systems in shiftwork and dementia. We are also identifying and validating a series of biomarkers to measure circadian phase and sleepiness under real-world conditions including lipidomics, metabolomics and urinomics and assessing other real-time circadian assessment technologies.

With the Harvard Work Hours Health and Safety Group, we assess the impact of extended work hours on health and safety of workers and the public. Our studies include the development of interventions that reduce extended duration work hours, fatigue and medical errors in hospital residents, and the implementation of large-scale occupational fatigue management and sleep disorders screening programs in police and firefighters nationwide.

Contato

Circadian Physiology Program
Division of Sleep and Circadian Disorders,
Departments of Medicine and Neurology
Brigham and Women’s Hospital
221 Longwood Avenue, RF-489
Boston, MA 02115
Tel: 617 732 4977
Fax: 617 732 4015
Email: [email protected]

Group Members

Circadian Physiology Program Group at the 2018 Sleep Health and Benefits Dinner: (L-R) Shadab A. Rahman, Leilah K. Grant, Brianne A. Kent, Melissa A. St. Hilaire, Steven W. Lockley, Ph.D.

Faculty

Steven W. Lockley, Ph.D.
Director, Circadian Physiology Program
Neuroscientist, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Associate Professor of Medicine, Harvard Medical School
Professor and VC Fellow, Surrey Sleep Research Centre, University of Surrey, UK

Shadab A. Rahman, Ph.D., M.P.H.
Associate Neuroscientist, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Instructor in Medicine, Harvard Medical School

Melissa A. St. Hilaire, Ph.D.
Associate Biostatistician, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Instructor in Medicine, Harvard Medical School

Research Fellows

Brianne A. Kent, Ph.D.
Research Fellow in Medicine, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Research Fellow in Medicine, Harvard Medical School

Leilah K. Grant, Ph.D.
Research Fellow in Medicine, Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital
Research Fellow in Medicine, Harvard Medical School

Research Assistant
Affiliated Faculty

Shantha M. W. Rajaratnam, Ph.D.
Professor, Monash University, Australia
Sleep and Circadian Rhythms Program
School of Psychological Sciences
Deputy Head, School of Psychological Sciences
Deputy Director, Turner Institute for Brain and Mental Health
Lecturer in Medicine (Academic, part-time), Harvard Medical School

Former Faculty and Fellows
  • Adriana Lira-Oliver, D.Des.
  • Joshua J. Gooley, Ph.D.
  • Eliza Van Reen, Ph.D.
  • Kate E. Crowley, Ph.D.
  • Brian K. Abaluck, M.D.
  • Melanie Rüger, Ph.D.
  • Joseph T. Hull, Ph.D.
  • Erin E. Flynn-Evans, Ph.D.
Former and Current (*) PhD students
  • Joseph T. Hull (in collaboration with University of Surrey)
  • Erin E. Flynn-Evans (in collaboration with University of Surrey)
  • Julia Shekleton (in collaboration with Monash University)
  • Suzanne Ftouni (in collaboration with Monash University)
  • María L. Ámundadóttir (in collaboration with EPFL)
  • Simonne Cohen (in collaboration with Monash University)
  • Leilah K. Grant (in collaboration with Monash University)
  • Julia E. Stone (in collaboration with Monash University)
  • *Saranea Ganesan (in collaboration with Monash University)
  • *Laura J. Connolly (in collaboration with Monash University)
  • *Lauren J. Bulfin (in collaboration with Monash University)
  • *Lauren A. Booker (in collaboration with IBAS and Monash University)
Collaborators

Brigham and Women’s Hospital, Boston

  • Laura K. Barger, Ph.D.
  • Charles A. Czeisler, Ph.D., M.D.
  • Hadine Joffe, M.D.
  • Elizabeth B. Klerman, M.D., Ph.D.
  • Bruce S. Kristal, Ph.D.
  • Christopher P. Landrigan, M.D., M.P.H.
  • Julian N. Robinson, M.D.
  • Jason P. Sullivan, B.S.
Current National and International Collaborators
  • George C. Brainard, Ph.D., Thomas Jefferson University, Philadelphia
  • Derk-Jan Dijk, Ph.D., Surrey Sleep Research Centre, University of Surrey, UK
  • Erin E. Flynn-Evans, Ph.D., NASA Ames, Moffett Field
  • Jennie Ponsford, Ph.D., Monash University, Melbourne, Australia
  • Christoph Reinhart, Ph.D., MIT, Cambridge
  • John Spengler, Ph.D., and Jose Guillermo (Memo) Cedeno Laurent, HSPH, Boston
  • Paula A. Witt-Enderby, Ph.D., Duquesne University, Pittsburgh
Selected Recent Publications
  1. Lockley SW. Guideline for authors: Measuring melatonin in humans. Journal of Pineal Research 2020, in press. PMID: 32344453
  2. Rahman SA, Rood D, Trent N, Solet J, Langer EJ*, Lockley SW*. Manipulating sleep duration perception changes cognitive performance – An exploratory analysis. Journal of Psychosomatic Research 2020 132. in press.
  3. Klerman EB, Rahman SA, St Hilaire MA. What time is it? A tale of three clocks, with implications for personalized medicine. Journal of Pineal Research 2020 68(4):e12646.
  4. Grant LK, Gooley JJ, St Hilaire MA, Rajaratnam SMW, Brainard GC, Czeisler CA, Lockley SW, Rahman SA. Menstrual phase-dependent differences in neurobehavioral performance: The role of temperature and the progesterone/estradiol ratio. Sleep 2020 43(2). pii: zsz227.
  5. Booker LA, Barnes M, Alvaro P, Collins A, Chai-Coetze CL, McMahon M, Lockley SW, Rajaratnam SMW, Howard ME. Sletten TL. The role of sleep hygiene in the risk of Shift Work Disorder in nurses. Sleep 2020 43(2). pii: zsz228. PMID: 31637435
  6. Rahman SA, Wright Jr KP, Lockley SW, Czeisler CA, Gronfier C. Characterizing the temporal dynamics of melatonin and cortisol changes in response to nocturnal light exposure. Scientific Reports 2019 9(1):19720. PMID: 31873098 PMCID: PMC6928018
  7. Peterson SA*, Wolkow AP*, Lockley SW, O’Brien CS, Qadri S, Sullivan JP, Czeisler CA, Rajaratnam SMW, Barger LK. Associations between shift work characteristics, shift work schedules, sleep and burnout in North American police officers: a cross-sectional study. BMJ Open 2019 9(11):e030302. PMID: 31791964 PMCID: PMC6924705
  8. St. Hilaire MA, Kristal BS, Rahman SA, Sullivan JP, Quackenbush J, Duffy JF, Barger LK, Gooley JJ, Czeisler CA, Lockley SW. Using a single daytime performance test to identify most individuals at high-risk for performance impairment during extended wake. Scientific Reports 2019 9(1):16681. PMID: 31723161 PMCID: PMC6853981
  9. Kronauer RE*, St Hilaire MA*, Rahman SA, Czeisler CA, Klerman EB. An exploration of the temporal dynamics of circadian resetting responses to short- and long-duration light exposures: cross-species consistencies and differences. Journal of Biological Rhythms 2019 in press. PMID: 31368391
  10. Rahman SA, Grant LK, Gooley JJ, Rajaratnam SMW, Czeisler CA, Lockley SW. Endogenous circadian regulation of female reproductive hormones. Journal of Clinical Endocrinology and Metabolism 2019 104(12):6049-6059. PMID: 31415086
  11. Rahman SA, Bibbo C, Olcese J, Czeisler CA, Robinson JN, Klerman EB. Relationship between endogenous melatonin concentrations and uterine contractions in late third trimester of human pregnancy. Journal of Pineal Research 2019 66(4):e12566. PMID: 30739346
  12. Gladanac B, Jonkman J, Shapiro CM, Brown TJ, Ralph MR, Casper RF, Rahman SA. Removing short wavelengths from polychromatic white light attenuates circadian phase resetting in rats. Frontiers in Neuroscience 2019 13:954. PMID: 31551702
  13. Stone JE, Aubert XL, Maass H, Phillips AJK, Magee M, Howard ME, Lockley SW, Rajaratnam SMW, Sletten TL. Application of a limit-cycle oscillator model for prediction of circadian phase in rotating night shift workers. Scientific Reports 2019 9(1):11032. PMID: 31363110 PMCID: PMC6667480
  14. Stone JE, Phillips AJK, Ftouni S, Magee M, Howard M, Lockley SW, Sletten TL, Anderson C, Rajaratnam SMW, Postnova S. Generalizability of a neural network model for circadian phase prediction in real-world conditions. Scientific Reports 2019 9(1):11001. PMID: 31358781 PMCID: PMC6662750
  15. Phillips AJK*, Vidafar P*, Burns AC, McGlashan EM, Anderson C, Rajaratnam SMW, Lockley SW, Cain SW. High sensitivity and interindividual variability in the response of the human circadian system to evening light. Proceedings of the National Academy of Science USA 2019 116(24):12019-12024. PMID: 31138694 PMCID: PMC6575863
  16. Ganesan S, Magee M, Stone JE, Mulhall MD, Collins A, Howard ME, Lockley SW, Rajaratnam SMW, Sletten TL. The impact of shiftwork on sleep, alertness and performance in healthcare workers. Scientific Reports 2019 9(1):4635. PMID: 30874565 PMCID: PMC6420632
  17. Grant LK, Ftouni S, Nijagal B, De Souza DP, Tull D, McConville MJ, Rajaratnam SW, Lockley SW, Anderson C. Circadian and wake-dependent changes in human plasma polar metabolites during prolonged wakefulness: A preliminary analysis. Scientific Reports 2019 9(1):4428. PMID: 30872634 PMCID: PMC6418225
  18. St. Hilaire MA, Anderson C, Anwar J, Sullivan JP, Cade BE, Flynn-Evans EE, Czeisler CA, Lockley SW for the Harvard Work Hours Health and Safety Group. Brief (<4 hour) sleep episodes are insufficient for restoring performance in first-year resident physicians working overnight extended-duration work shifts. Sleep 2019 42(5). PMID: 30794317
  19. Sletten TL, Magee M, Murray JM, Gordon CJ, Lovato N, Kennaway DJ, Gwini SM, Bartlett DJ, Lockley SW, Lack LC, Grunstein RR, Rajaratnam SMW for the Delayed Sleep on Melatonin (DelSoM) Study Group. Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. PLoS Medicine 2018 15(6):e1002587. PMID: 29912983 PMCID: PMC6005466
  20. Vidafar P, Gooley JJ, Burns AC, Rajaratnam SMW, Rueger M, Van Reen E, Czeisler CA, Lockley SW, Cain SW. Increased vulnerability to attentional failure during acute sleep deprivation in women depends on menstrual phase. Sleep 2018 41(8). PMID: 29790961
  21. Rahman SA, St. Hilaire MA, Gronfier C, Chang AM, Santhi N, Czeisler CA, Klerman EB, Lockley SW. Functional decoupling of melatonin suppression and circadian phase resetting in humans. Journal of Physiology 2018 596(11):2147-2157. PMID: 29707782
  22. Hull JT, Czeisler CA, Lockley SW. Suppression of melatonin secretion in totally visually blind people by ocular exposure to white light: Clinical characteristics. Ophthalmology 2018 125(8):1160-1171. PMID: 29625838
  23. Watson LA, Phillips AJK, Hosken IT, McGlashan EM, Anderson C, Lack LC, Lockley SW, Rajaratnam SMW, Cain SW. Increased sensitivity of the circadian system to light in Delayed Sleep-Wake Phase Disorder. Journal of Physiology 2018 596(24):6249-6261. PMID: 30281150
  24. Abeysuriya RG, Lockley SW, Robinson PA, Postnova S. A unified model of melatonin, 6-sulfatoxymelatonin, and sleep dynamics. Journal of Pineal Research 2018 64(4):e12474. PMID: 29437238
  25. St. Hilaire MA, Rahman SA, Gooley JJ, Witt-Enderby PA, Lockley SW. Relationship between melatonin and bone resorption rhythms in premenopausal women. Journal of Bone and Mineral Metabolism 2019 37(1):60-71. PMID: 29318392
  26. Anderson C, Ftouni S, Ronda JM, Rajaratnam SMW, Czeisler CA, Lockley SW. Self-reported drowsiness and safety outcomes while driving after an extended duration work shift in trainee physicians. Sleep 2018 41(2) zsx195. PMID: 29281091
  27. Cohen S*, Fulcher BD*, Rajaratnam SMW, Conduit R, Sullivan JP, St Hilaire MA, Philips AJK, Loddenkemper T, Kothare SV, McConnell K, Braga-Kenyon P, Ahearn W, Schlesinger A, Potter J, Bird F, Cornish KM, Lockley SW. Sleep patterns predictive of daytime challenging behavior in individuals with low-functioning autism. Autism Research 2018 11(2):391-403. PMID: 29197172
  28. Kelley P, Lockley SW, Kelley J, Evans MDR. Is 8:30 a.m. still too early to start school? A 10:00 a.m. school start time improves health and performance of students aged 13-16. Frontiers in Human Neuroscience 2017 11:588. PMID: 29276481 PMCID: PMC5727052
  29. Cohen S, Fulcher BD, Rajaratnam SMW, Conduit R, Sullivan JP, St Hilaire MA, Phillips AJ, Loddenkemper T, Kothare SV, McConnell K, Ahearn W, Braga-Kenyon P, Schlesinger A, Potter J, Bird F, Cornish KM, Lockley SW. Behaviorally-determined sleep phenotypes are robustly associated with adaptive functioning in individuals with low-functioning autism. Scientific Reports 2017 7(1):142287. PMID: 29079761 PMCID: PMC5660229
  30. Flynn-Evans EE, Shekleton JA, Miller B, Epstein LJ, Kirsch D, Brogna LA, Burke LM, Bremer E, Murray JM, Gehrman P, Rajaratnam SMW, Lockley SW. Circadian phase and phase angle disorders in primary insomnia. Sleep 2017 40(12). PMID: 29029340
  31. Phillips AJK*, Clerx WM*, O’Brien CS, Sano A, Barger LK, Picard RW, Lockley SW, Klerman EB, Czeisler CA. Irregular sleep/wake patterns are associated with poorer academic performance and delayed circadian and sleep/wake timing. Scientific Reports 2017 7(1):3216. PMID: 28607474 PMCID: PMC5468315
  32. Rahman SA, St. Hilaire MA, Lockley SW. The effects of spectral tuning of evening ambient light on melatonin suppression, alertness and sleep. Physiology and Behavior 2017 177: 221-229. PMID: 28472667
  33. Rahman SA, St. Hilaire MA, Chang AM, Santhi N, Duffy JF, Kronaeur RE, Czeisler CA, Lockley SW, Klerman EB. Circadian phase resetting by a single short-duration light exposure. JCI Insight 2017 2(7):e89494. PMID: 28405608 PMCID: PMC5374060
  34. St. Hilaire MA*, Rüger M*, Fratelli F, Hull JT, Phillips AJK, Lockley SW. Modeling neurocognitive decline and recovery during repeated cycles of extended sleep and chronic sleep deficiency. Sleep 2017 40(1). doi: 10.1093/sleep/zsw009. PMID: 28364449
  35. Murray JM, Sletten TL, Magee M, Gordon C, Lovato N, Bartlett DJ, Kennaway DJ, Lack LC, Grunstein RR, Lockley SW, Rajaratnam SMW. Delayed Sleep on Melatonin (DelSoM) Study Group. Prevalence of circadian misalignment and its association with depressive symptoms in delayed sleep phase disorder. Sleep 2017 40(1). doi: 10.1093/sleep/zsw002. PMID: 28364473
  36. Sullivan JP, O’Brien CS, Barger LK, Rajaratnam SMW, Czeisler CA, Lockley SW The Harvard Work Hours, Health and Safety Group. Randomized, prospective study of the impact of a workplace-based sleep health program on firefighter injury and disability. Sleep 2017 40(1). doi: 10.1093/sleep/zsw001. PMID: 28364446
  37. Grima NA, Ponsford JL, St Hilaire MA, Mansfield D, Rajaratnam SM. Circadian melatonin rhythm following traumatic brain injury. Neurorehabilitation and Neural Repair 2016 30(10):972-977. PMID: 27221043
  38. Rahman SA, Castanon-Cervantes O, Scheer FAJL, Shea SA, Czeisler CA, Davidson AJ, Lockley SW. Endogenous circadian regulation of pro-inflammatory cytokines and chemokines in the presence of bacterial lipopolysaccharide in humans. Brain, Behavior, and Immunity 2015 47:4-13. PMID: 25452149.
  39. Barger LK, Rajaratnam SM, Wang W, O'Brien CS, Sullivan JP, Qadri S, Lockley SW, Czeisler CA The Harvard Work Hours Health and Safety Group. Common sleep disorders increase risk of motor vehicle crashes and adverse health outcomes in firefighters. Journal of Clinical Sleep Medicine 2015 11(3):233-240. PMID: 25580602. PMCID: PMC4346644.
  40. St. Hilaire MA, Lockley SW. Caffeine does not entrain the circadian clock but improves daytime alertness in blind patients with non-24-hour rhythms [Brief Communication]. Sleep Medicine 2015 16(6):800-4. PMID: 25891543 PMCID: PMC4465963
  41. Lockley SW, Dressman MA, Licamele L, Xiao C, Fisher DM, Flynn-Evans EE, Hull JT, Torres R, Lavedan C, Polymeropoulos MH. Two multicentre randomised trials of tasimelteon for treatment of Non-24-Hour Sleep-Wake Disorder in the blind. The Lancet 2015 386(10005): 1754-1764. PMID: 26466871
Selected Recent Research Support

Seoul Semiconductor (PI: Rahman) 01/11/19-01/10/24
Investigator-initiated study “Effects of daytime lighting conditions on students' cognitive performance”
The goal is to assess the role light spectrum and intensity on the alerting effects of daytime light exposure.

FAA (Co-PIs: Klerman, Czeisler) 09/18/19-09/17/21
FAA “Comparison across multiple types of sleep deprivation”.
This contracted work will collect data for the FAA for discovery of biomarkers associated with neurobehavioral or cognitive impairment during sleep loss and mistimed sleep. Role: Co-Investigator

PNNL (PI: Rahman) 09/10/19-08/31/21
Investigator-initiated study “analyzing de-identified patient data for an inpatient behavioral health unit research”
The goals are to assess the role of light on health outcomes in an inpatient facility. Role: Co-Investigator

1R21NR018974 (PI: St Hilaire) 09/25/19-07/31/21
NINR ‘Urine metabolomics to estimate internal clock time’
The goals are to develop a feasible method to measure circadian phase accurately and reliably using non-invasive urinomics. Role: Co-Investigator

F.lux Software, LLC (PI: Lockley) 08/28/15-08/27/20
Investigator-initiated study “Measuring the effects of light from electronic devices on sleep”
We propose to conduct a randomized clinical trial on the effects of reducing blue content of light emitted from electronic devices on sleep using the F.Lux software.

NNX15AC14G (Co-PIs: Brainard, Lockley) 12/01/14-09/30/20
NASA “Testing solid state lighting countermeasures to improve circadian adaptation, sleep, and performance during high fidelity analog and flight studies for the International Space Station”.

NNX15AM28G (PI: Lockley) 08/13/15-06/30/20
NASA “Lighting Protocols for Exploration – HERA Campaign”
The study will examine the feasibility and efficacy of a Dynamic Lighting System to improve alertness, sleep and circadian rhythms in the Human Exploration Research Analog.

Recently completed

NNX14AK53G (PI: Lockley) 08/01/14-01/31/20 (NCE)
NSBRI “Development and testing of biomarkers to determine individual astronauts’ vulnerabilities to behavioral health disruptions”
This study will evaluate biomarkers that will test the sensitivity of various sleep and circadian challenges to differentiate individuals.

Midwest Lighting Institute (PI: Rahman) 01/01/18-12/31/19
“Senior care facility lighting to improve health, safety and energy efficiency”.
The goal of this project is to examine the impact of a dynamic lighting intervention on the health and safety of seniors living in care homes. Role: Co-Investigator.

1R01HL132556 (PI: Kristal) 04/18/16-03/31/20
NHLBI “Circadian Lipidomics in Constant Routine, Forced Desynchrony, and Non-lab Setting”
The goals of this project are to identify, optimize, validate, and to cross-validate a set of nested plasma lipidomics-based biomarker profiles that report circadian phase.


Resumo

The core plant circadian oscillator is composed of multiple interlocked transcriptional-translational feedback loops, which synchronize endogenous diel physiological rhythms to the cyclic changes of environmental cues. PSEUDO-RESPONSE REGULATORS (PRRs) have been identified as negative components in the circadian clock, though their underlying molecular mechanisms remain largely unknown. Here we found that a subfamily of zinc finger transcription factors, B-box (BBX)-containing proteins, have a critical role in fine-tuning circadian rhythm. We demonstrated that overexpressing Arabidopsis thaliana BBX19 e BBX18 significantly lengthened the circadian period, while the null mutation of BBX19 accelerated the circadian speed. Moreover, BBX19 and BBX18, which are expressed during the day, physically interacted with PRR9, PRR7, and PRR5 in the nucleus in precise temporal ordering from dawn to dusk, consistent with the respective protein accumulation pattern of PRRs. Nossa análise transcriptômica e genética indicou que BBX19 e PRR9, PRR7 e PRR5 inibiram cooperativamente a expressão de genes do relógio de fase matinal. As proteínas PRR afetaram o recrutamento de BBX19 para o CCA1, LHY, e RVE8 promotores. Coletivamente, nossos resultados mostram que o BBX19 interage com PRRs para orquestrar os ritmos circadianos e sugere o papel indispensável dos reguladores transcricionais no ajuste fino do relógio circadiano.


Você está no colchão certo para suas necessidades?

Tudo o que mencionamos acima pressupõe que você não está dormindo em uma cama tão desconfortável que você passa a noite toda se revirando.

Pode surpreendê-lo saber que podemos realmente localizar o melhor colchão para você com base em seus fatores, como posição de dormir, peso, formato do corpo e muito mais.

Por exemplo, travessas laterais tendem a preferir colchões mais macios. A maciez de um colchão macio ajuda a aliviar os pontos comuns de pressão em seus ombros e quadris.

Encontrar o colchão certo para você o ajudará a praticar melhores hábitos de sono e, depois que o relógio for zerado, manterá um horário de sono consistente.

Você já teve que zerar o relógio do sono antes? Que truques funcionaram para você ao tentar redefinir seu relógio de hibernação?

Este artigo é para fins informativos e não deve substituir o conselho de seu médico ou outro profissional médico.

Sobre o autor

Rosie Osmun contribui regularmente para o blog Amerisleep escrevendo sobre tópicos, incluindo redução da dor nas costas durante o sono, os melhores jantares para dormir melhor e melhorando a produtividade para aproveitar ao máximo as manhãs. Ela acha a ciência do sono fascinante e adora pesquisar e escrever sobre camas. Rosie também é apaixonada por viagens, idiomas e história.