If you have an article of interest for this section, please send article link to Stu Brody
Articles for Clocks in the News
Created by
Prof. Stu Brody, Dr. Anna Kriebs, and Dr. Drew Duglan
Timeout for glioblastoma
by: D.Duglan | Sep 2019
Glioblastoma represents the most common and aggressive form of brain cancer, with high rates of relapse following surgery, attributed in part to the underlying population of glioblastoma stem cells left behind. A recent study, published in the journal Cancer Discovery, has now discovered an overactive clock in these glioblastoma stem cells; a biological model which has remained relatively unexplored in the circadian field. CCB board member Prof. Steve Kay, along with Dr. Jeremy Rich and colleagues, assessed the clock machinery of tumor stem cells isolated from glioblastoma patients, observing that cancer cell growth was heavily dependent on the core molecular clock proteins BMAL1 and CLOCK. By genetically disrupting these clock components, the team revealed that metabolic processes within the stem cells were altered, thereby strangling the supply of energy required for normal cancer proliferation. To assess the translational potential of these initial findings, the researchers then blocked BMAL1 and CLOCK in stem cells by delivery of small-molecule drugs, demonstrating similar suppressive effects on cancer cell survival. This work highlights the reprogramming of clock-controlled pathways that may occur in the unique population of self-renewing glioblastoma stem cells. Furthermore, the discoveries add to the notion that modifying the circadian machinery in a cell-selective manner could offer a new therapeutic paradigm for sufferers of hard-to-treat cancers.
ScienceDaily
https://www.sciencedaily.com/releases/2019/08/190827095051.htm
Neuroscience News
https://neurosciencenews.com/circadian-clock-glioblastoma-14808/amp/
Sleep Review
http://www.sleepreviewmag.com/2019/08/circadian-clock-brain-cancer/
Original Article
https://cancerdiscovery.aacrjournals.org/content/early/2019/08/22/2159-8290.CD-19-0215.full-text.pdf
Stem cell gene makes the master clock tick
by: D.Duglan | Apr 2019
In mammals the suprachiasmatic nucleus (SCN) of the brain is home to the circadian pacemaker – the “master clock.” While these clock neurons drive rhythms that ultimately synchronize the rest of the body, the molecular machinery that regulates this process is still not fully understood. A new study, published in the journal Cell Reports, has demonstrated that this central biological clock can be set by a gene normally associated with stem cells. Arthur Cheng and colleagues focused on a gene called SOX2, which they were surprised to find was expressed in the neurons of the SCN region and had the ability to activate the core clock gene Period2. By selectively deleting SOX2 from these neurons the team observed that the strength of the cellular rhythms was significantly reduced, as well as the abundance of neuropeptides that are normally released as messenger signals. To understand how this gene could influence daily behavior, researchers monitored the activity cycles of mice that genetically lacked SOX2 in their SCN. Under normal conditions these mice showed disrupted sleep-wake behavior, moreover, they were less able to adapt when subjected to experimental jet lag. This work reveals that SOX2 may control the landscape of gene expression in the master clock, which can ultimately determine coordinated physical behaviors. Given the known role of SOX2 in embryonic development, this study may also have implications for how our internal timekeeping system is formed from a young age.
Read more here:
Science Daily
https://www.sciencedaily.com/releases/2019/03/190327152857.htm
Phys.org
https://phys.org/news/2019-03-master-pacemaker-biological-clocks.html
Timing exercise to beat jet lag
by: D.Duglan | Mar 2019
Circadian disruption can occur when our internal clock is misaligned with environmental schedules, the most common examples being exposure to jet-lag and shift-work. This has prompted the investigation of both therapeutic agents and lifestyle interventions that have the capacity to shift our circadian clock and aid with adaptation to new time zones. A new study, published in The Journal of Physiology, has reinforced the utility of exercise as a time cue for the body, revealing that the circadian clock of human subjects could be advanced or delayed depending on the timing of the exercise bout. Shawn Youngstedt and colleagues recruited 101 healthy participants, who were either young (18-30 yr) or old (59-75 yr) and a mix of men and women. Subjects were admitted to a controlled laboratory for 5 days under constant environmental conditions, during which time they were asked to perform one hour of moderate treadmill exercise at various points throughout the day. Each subject’s daily biological rhythm was determined from urinary levels of melatonin, measured every 90 minutes. Researchers found that participants’ internal clock was advanced when exercise was performed at 7am and 1-4pm; it was delayed when exercising between 7pm and 10pm. The same patterns were observed regardless of age or sex. This work supports the notion that prior early morning exercise is effective for countering jet-lag from Eastbound transmeridian travel, whereas prior evening exercise would help with Westbound travel. Further work should establish if the same phase-shifting effects can be achieved in individuals who are less healthy or physically active.
Read more here:
EurekAlert
https://eurekalert.org/pub_releases/2019-02/tps-eim021819.php
TIME
http://time.com/5533388/best-time-to-exercise/
Medical News Today
https://www.medicalnewstoday.com/articles/324520.php
Original Article
https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP276943
Fat clocks can still run on time
by: D.Duglan | Mar 2019
Understanding the function of tissue-specific clocks in humans remains a significant challenge, largely due to the difficulty in collecting a time-course of multiple samples. A new study, published in the journal Scientific Reports, has explored the rhythmicity of fat tissue by taking biopsies from healthy subjects throughout the day. Skevoulla Christou and colleagues admitted 7 male participants to a controlled laboratory, where they were subjected to a 37-hour “constant routine.” During this time, light-dark, fasting-feeding and sleep-wake cycles are held constant, thereby minimizing the effects of the environment and behavior, allowing one to attribute results to primarily the internal circadian system. Throughout this routine, biopsy samples of white adipose tissue were taken from the upper gluteal region every 6 hours, which were then examined for rhythmic genes. Researchers found 727 genes that had their own independent rhythm unique to fat cells; at least two-thirds of these genes showed peak expression in the evening hours, while the remainder peaked in the morning. Based on these rhythms, network analysis has predicted that fat tissue undergoes considerable cyclical changes in metabolic pathways, such as those involved with lipids and amino acids. This work further expands the view of fat tissue as a key endocrine organ and may enhance our understanding of how circadian disruption can drive weight gain.
Read more here:
ScienceDaily
https://www.sciencedaily.com/releases/2019/02/190225075605.htm
Genetic Engineering and Biotechnology News
https://www.genengnews.com/topics/omics/fat-cell-genes-punch-the-clock-to-carry-out-key-metabolic-functions/
Original Article
https://www.nature.com/articles/s41598-019-39668-3?_ga=2.175274976.39396592.1551294033-135744773.1551294033
Mental health linked to chronotype
by: D.Duglan | Feb 2019
Whether you’re an early bird or a night owl is a behavioral indicator of the individual’s internal circadian clock. The human preference for earlier or later sleep timing, known as chronotype, was previously known to be influenced by 24 genetic variants. Now, a recent study published in the journal Nature Communications, has expanded this genome-wide data set and provided key insights into the relationship between chronotype and disease risk. Samuel Jones and colleagues studied genetic data from nearly 700 000 participants (sourced from UK Biobank and 23andMe Inc.), subsequently cross-referencing this with their self-reported chronotype and objective sleep activity tracking data from 85 000 individuals. Researchers identified a new total of 351 different genetic markers that were associated with being either a “morning-person” or “evening-person.” These gene variants were also associated with the objective measures of sleep timing, though not with sleep quality or duration. Interestingly, the 5% of subjects with the most morning-type genetic profile exhibited sleep timing that was shifted 25 minutes earlier than the 5% of individuals with the least morning-type genetic signature. Being a morning person also appeared to be correlated with a lower risk of schizophrenia and depression, but not obesity or type 2 diabetes. To date, this is the largest data set to explore the genetic links between sleep timing and mental health. Future studies should elucidate whether a disparity between a person’s socially-enforced sleeping routine and their genetic chronotype also leads to the same increase in disease risk.
Read more here:
New York Times
https://www.nytimes.com/2019/01/30/health/morning-person-genes.html
Sleep Review
http://www.sleepreviewmag.com/2019/01/night-owl-chronotype-mental-health/
CNN
https://www.cnn.com/2019/01/29/health/circadian-rhythms-genetic-study/index.html
Original Article
https://www.nature.com/articles/s41467-018-08259-7
Gene-editing monkeys to make clockless clones
by: D.Duglan | Feb 2019
Recent scientific breakthroughs in CRISPR-mediated gene-editing have raised numerous ethical concerns over its potential application to future human babies. Recent work in China has now revealed that clock genes can be edited in non-human primates to produce abnormal circadian behavior, moreover, that these monkeys can be physically cloned. Dual studies, published in the journal National Science Review detail the approach, which first involved editing the internal clock of fertilized embryos by deleting the core clock gene BMAL1. Adult macaques from these embryos exhibited severe signs of circadian disruption, including reduced sleep, abnormal daily hormonal patterns and depression. Researchers then took skin cells (fibroblasts) from one of these “donor” monkeys, removing the DNA and injecting it into new monkey oocytes (egg cells). These re-engineered future embryos were then transferred to the wombs of surrogate mothers, producing a total of 5 successful monkey clones, all with the same gene-edited clock of the original donor. The researchers hope to establish this approach as a new model of studying human disease progression and for testing potential therapies.
Read more here:
EurekAlert
https://www.eurekalert.org/pub_releases/2019-01/scp-gdm012119.php
TheScientist
https://www.the-scientist.com/news-opinion/clones-made-of-crispred-monkeys-65387
The Independent
https://www.independent.co.uk/news/science/monkey-clones-gene-editing-china-mental-health-disease-a8743096.html
Original Articles
https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwz002/5290357
https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwz003/5290358
Support cells of the brain can direct circadian rhythms
by: D.Duglan | Jan 2019
Just as neurons of the suprachiasmatic nucleus (SCN) in the brain are understood to act as the master internal clock, neighboring astrocytes have traditionally been thought of as merely permissive support cells. However, a new study published in the journal Science has now demonstrated that astrocytes themselves can direct biological time-keeping. Marco Brancaccio and colleagues first conducted bioluminescent imaging of brain sections, finding that both neurons and astrocytes within the SCN had their own functionally distinct circadian clocks, which happened to be active at different times of the day. Researchers then used mice with a genetically-silenced internal clock in all tissues, which typically display disrupted rhythms of daily behavior. By restoring the clock specifically in just astrocytes, the team observed that these mice had reinstated daily activity patterns. The findings reveal how important astrocyte cells are for independently directing SCN rhythms, which may be mediated via the chemical messenger glutamate. Studies like this add a new layer to our model of integrated circadian timing; moreover, they help to challenge the purely neuron-centric view of physiology and behavior.
Read more here:
EurekAlert
https://www.eurekalert.org/pub_releases/2019-01/mrc-nrf010919.php
Science Daily
https://www.sciencedaily.com/releases/2019/01/190110141818.htm
Technology Networks
https://www.technologynetworks.com/neuroscience/news/keeping-time-in-the-brain-313789
Original Article
http://science.sciencemag.org/content/363/6423/187
Shellfish that use the moon to tell the time
by: D.Duglan | Jan 2019
For many people, the term “biological rhythm” might be thought of as either a daily (circadian) or seasonal (circannual) rhythm. For studies on marine ecosystems, this term also often encompasses tidal rhythms, but rarely ever lunar rhythms, which remain largely unknown. A recent study published in the journal Biology Letters has demonstrated that oysters alter their behavior depending on the phase of the moon. Laura Payton and Damien Tran used electrodes to continuously track the opening of Pacific oysters (Crassostrea gigas) submerged off the French coast during 3.5 lunar cycles. Researchers found that the oysters’ valves were most open immediately preceding and during a new moon, suggesting that mollusks can sense variations in nocturnal light, which may be an evolutionary adaptation to associated changes in food availability. Interestingly however, valve opening also differed significantly between the first and third quarter moon phases, when moonlight intensity is very similar. This finding implies that oysters possess an internal lunar clock which synchronizes behavior based on additional aspects of the ecological cycle and not just light. Such behaviors are integral to oyster survival given that valve activity is tightly linked to gene expression and diverse physiological processes. It remains to be seen how modern human activity (e.g. coastal lighting) may be influencing these cycles and affecting the overall sustainability of various crustacean species.
Read more here:
https://phys.org/news/2019-01-evidence-oysters-syncing-valve-behavior.html
The Guardian
https://www.theguardian.com/food/2019/jan/09/moon-influences-opening-of-oyster-shells
Original article
https://royalsocietypublishing.org/doi/10.1098/rsbl.2018.0299
Delaying school start times advances academic performance
by: D.Duglan | Dec 2018
Many parents know the struggle in getting their children out of bed for school in the morning. Despite the notion of “laziness” during adolescence, the preference for sleeping-in is due to a delay in our internal clock during this developmental stage. The propensity for adolescents to be “night-owls” is not appreciated in high school schedules, where early start times typically force students into a pattern of chronic sleep deprivation. A recent study, published in the journal Science Advances, has demonstrated the real-world benefits of delaying school start times for grade performance and overall class attendance. Gideon Dunster and colleagues studied two high schools in Seattle, where student participants were fitted with wrist activity watches to monitor physical movement, sleep and light exposure. Academic performance in the same early morning class was then assessed both before and after the shift in school start times, which changed from 07:50am to 08.45am. Researchers found that the shift in school timing increased the daily sleep duration of students by 34 minutes, moreover, that this was associated with a 4.5% increase in the median grades for that semester. Interestingly, this initiative also improved early class attendance specifically in the school that was more economically disadvantaged. These findings reveal that such a biologically simple (albeit socially challenging) intervention can have profound consequences for learning and memory, and can improve equality of opportunity between students of different socioeconomic backgrounds.
Read more here:
New York Times
https://www.nytimes.com/2018/12/12/well/mind/starting-school-later-really-does-help-teens-get-sleep.html
ScienceAlert
https://www.sciencealert.com/in-seattle-starting-school-later-has-boosted-sleep-time-grades-and-attendance
Original Article
http://advances.sciencemag.org/content/4/12/eaau6200
Spinal cord injury leads to discordant body clocks
by: D.Duglan | Dec 2018
Although the central nervous system comprises both brain and spinal cord, the role of the latter in controlling the internal clock has been relatively under-studied. Breaking new research published in the journal eNeuro has demonstrated that moderate injury to the spinal cord of rats alters key outputs of their circadian system. Dr. Andrew Gaudet and colleagues surgically lesioned the thoracic (middle) portion of the spinal cord and then monitored rhythms in circulating steroid hormones, body temperature and physical activity, all of which help to synchronize peripheral tissue clocks. Rhythms in all these measures remained abnormal up to 7 days post-surgery, moreover, in male rats (relative to female) the peak timing of body temperature was not restored until after 30 days post-surgery. Researchers also observed that the expression of circadian clock genes and inflammatory genes were disrupted in spinal tissue post-surgery, both at the site of the lesion, as well as in the lower lumbar region. Although this study was only acute in nature, the findings are consistent with human reports of long-term circadian disruption (sleep disturbance and impaired thermoregulation) following spinal cord or traumatic brain injuries. Future studies with animal models and human patients will determine how optimizing daily rhythms in light exposure, sleep, feeding and physical rehabilitation can aid in recovery from such trauma.
Read more here:
Science Daily
https://www.sciencedaily.com/releases/2018/12/181204155153.htm
EurekAlert!
https://www.eurekalert.org/pub_releases/2018-12/uota-sci120418.php
CU Boulder Today
https://www.colorado.edu/today/2018/12/03/spinal-injuries-throw-body-clocks-schedule-new-study-shows
Original Article
http://www.eneuro.org/content/early/2018/12/03/ENEURO.0328-18.2018
Liver Cancer Combatted by Clock Manipulation
by: D.Duglan | Nov 2018
The link between circadian disruption and cancer risk continues to grow, both in epidemiological reports and findings from basic biology. A new study, published in the journal Nature Communications, has revealed a potential role for the molecular clock in hepatocellular carcinoma (HCC), the third most common cause of cancer-related deaths worldwide. Dr. Kristin Eckel-Mahan and colleagues specifically investigated HNF4α (hepatocyte nuclear factor 4α), a transcription factor with diverse roles in liver function, which is often dysregulated in cases of HCC. Researchers demonstrated that mice with spontaneous HCC (following exposure to jet-lag) had high expression of this transcription factor in the tumor, but low levels of the circadian clock protein BMAL1. Moreover, this same pattern of expression was observed in tumor samples from human subjects with HCC. While HNF4α and BMAL1 normally co-exist in healthy liver cells, in HCC an incompatibility emerges, whereby HNF4α directly represses the transcription of BMAL1. To examine whether improving BMAL1 expression could reduce HCC severity in vivo, the team implanted mice with tumorigenic cells that contained rescued levels of BMAL1. The presence of BMAL1 almost completely abolished tumor growth in these mice by increasing the programmed death of cancerous cells. This work increases our understanding of HNF4α in HCC pathogenesis and highlights the possibility of targeting the circadian clock therapeutically to improve cancer prognosis.
Read more here:
Science Daily
https://www.sciencedaily.com/releases/2018/11/181108091241.htm
Sleep Review Mag
http://www.sleepreviewmag.com/2018/11/body-clock-liver-cancer-growth/
Original Article
https://www.nature.com/articles/s41467-018-06648-6
TimeSignature as a new blood test to read internal clocks
by: D.Duglan | Sep 2018
One of the challenges in human circadian studies is tracking an individual’s own internal clock, which traditionally requires hourly sampling of markers such as melatonin across the 24-hour day, which is expensive and invasive for the subject. A new study published in the journal PNAS, has unveiled TimeSignature – a new software tool with the ability to estimate our biological time from just two blood draws, which can be flexibly spaced 8-12 hours apart. Rosemary Braun and colleagues measured the expression of thousands of genes in the blood from their own cohort of healthy volunteers, as well as from three other independent datasets already published. They then developed a machine-learning algorithm to sift through the data and make predictions of circadian time based on genes with the strongest cyclical patterns. The best markers consist of a panel of ~40 genes, many of which have diverse roles, such as in metabolism or immune function. This efficient new test is accurate to within 2 hours of an individual’s circadian time and will be useful in determining when our internal clock is out of sync with the time of the external world. As the blood test becomes clinically available, more easily than ever before will researchers and physicians be able to optimize the timing of medical interventions and explore the links between circadian disruption and chronic disease
Read more here:
Futurity
https://www.futurity.org/circadian-rhythm-blood-test-1865492-2/
The Conversation
http://theconversation.com/simple-blood-test-could-read-peoples-internal-clock-102878
Northwestern University News Center
https://news.northwestern.edu/stories/2018/september/circadian-clock-blood-test/
Original Article
http://www.pnas.org/content/early/2018/09/05/1800314115
Clocks in the Clinic: The Future of Chronotherapeutics
by: D.Duglan | Jun 2018
At the heart of much of our research into circadian rhythms is the potential for viable chronotherapy, which broadly describes the translational impact of circadian biology on clinical outcomes. This concept has been highlighted in a recent Nature Medicine news feature, which neatly summarizes the current state of chronotherapy and considerations for future development and application.
An appreciation of circadian rhythms in drug efficacy may be traced back to the work of Franz Halberg in 1972, where he began examining the time of day effects of chemotherapeutic agents in cancer. Since then, similar experiments have been extended to other tumor types, moreover, it has inspired studies in the timing of various other interventions, such as immune system modulators, epilepsy drugs and even surgery outcomes. One of the chronobiologists currently leading the charge is John Hogenesch, Professor of Pediatrics at Cincinnati Children's Hospital Medical Center. His team has developed a bioinformatics tool called CYCLOPS (cyclic ordering by periodic structure), which has the capacity to map out the 24-hour expression cycles of various genes from human tissue samples. Many of these genes encode proteins that serve as targets for some of the most widely prescribed pharmaceutical drugs for common diseases. This technology is allowing the team to match relevant expression profiles with a library of already FDA-approved drugs, which could ultimately predict optimal treatment times to ensure both maximum efficacy and minimal off-target side effects. It’s an exciting proposition that either established standards of care or even treatment failures could be modified through simply adjusting their timing of administration. However, implementing chronotherapy in day-to-day clinical practice could be anything but simple. Factoring the time of day or an individual’s chronotype into treatment regimens could present big challenges for procedure scheduling, staff hours and patient compliance. Hopefully the social and economic burden of disease will win out against these hurdles and this cutting-edge work in chronotherapy will help transform medical care in the years to come.
Nature (Cancer chronotherapy)
https://www.nature.com/articles/d41586-018-04600-8
Phys.org (Body clock atlas for drug timing)
https://phys.org/news/2014-10-atlas-body-clock-gene-drug.html
Shedding Light Upon the Use of Melatonin as a Biomarker
by: D.Duglan | May 2018
Exposure to light during the night-time hours is known to inhibit melatonin production, as well as reset one’s circadian phase. Given that both phenomena are often correlated, melatonin suppression has traditionally been used as a simple experimental proxy for shifts in phase. However, a recent study published in the Journal of Physiology has challenged the assumption that the two are functionally coupled. A research team led by Dr. Shadab Rahman admitted 16 healthy participants to a light-controlled laboratory environment for a period of 9-10 days. Subjects were then exposed to nocturnal light stimuli of different durations, in either an intermittent or continuous fashion. The results showed that phase delay shifts increased with greater light exposure duration, irrespective of the type of exposure. In contrast, the extent of melatonin suppression depended on the light exposure sequence. Intermittent exposures caused disproportionately low levels of melatonin suppression, which remained the same across the different durations (see figure). This work suggests that phase resetting and melatonin suppression may be functionally independent and regulated through different physiological processes. The findings could help shape experimental design in future studies, especially those exploring the utility of light-therapy for individuals with a disrupted biological clock.
Read more here:
Science Daily
https://www.sciencedaily.com/releases/2018/04/180430075635.htm
EurekAlert
https://eurekalert.org/pub_releases/2018-04/tps-tro042518.php
Original article
https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP275501
Aggression Rises as the Sun Sets
by: D.Duglan | Apr 2018
Patients with dementia and Alzheimer’s often experience agitation during the early evening hours, a phenomenon known as “sundowning”. While this behavior displays a daily rhythm, up until now its potential regulation by the central circadian clock remained unknown. A recent study, published in the journal Nature Neuroscience, has demonstrated a circadian pattern of aggression propensity in mice and identified the neuronal circuitry responsible. Clifford Saper and colleagues initially observed that the tendency of cage “resident” male mice to display aggression towards male “intruder” mice was dependent on the time of day. The greatest engagement in attack behavior occurred in the early evening, whereas mice were the least aggressive in the early morning. This result was not simply due to the direct effects of light, since similar differences in aggression were observed in mice kept in constant darkness. Through genetic manipulation, the researchers disabled a population of GABAergic neurons in the suprachiasmatic nucleus (SCN), which are known to act as a relay for the outputs of the master clock. By inhibiting this neurotransmission, mice consequently lost the rhythmic changes in aggression. Using a tool known as optogenetics, the team went on to uncover a functional circuit connecting the SCN to a region of the brain called the ventromedial hypothalamus (VMH), which is known to drive attack behavior upon activation. The notion is that rhythmic activity of SCN neurons across the day alters the level of inhibitory input to the VMH, thereby gating the intensity and duration of aggressive conduct. This previously unrecognized pathway could be significant in understanding the pathology of certain neurodegenerative conditions and in designing novel interventions for improving patient quality of life.
Read more here:
Science Daily
https://www.sciencedaily.com/releases/2018/04/180409185309.htm
Medical News Today
https://www.medicalnewstoday.com/articles/321449.php
Genetic Engineering and Biotechnology News
https://www.genengnews.com/gen-news-highlights/cyclical-alzheimers-aggression-pathway-uncovered/81255675
The Independent
https://www.independent.co.uk/news/health/sunset-aggression-high-levels-evolution-dementia-sundowning-alzheimers-a8296471.html
Original Article
https://www.nature.com/articles/s41593-018-0126-0?_ga=2.77379805.957995016.1523922191-1678649917.1523922191
Social Jet Lag Tied to Lagging Academic Performance
by: D.Duglan | Apr 2018
Everyone enjoys a good sleep-in after the working week is done. However, such discrepancies in sleep timing and social schedules between working and free days contribute to the societal problem of “social jet lag.” Unlike brief periods of travel across time zones, this type of jet lag may persist long term throughout one’s career, leading to a chronically misaligned circadian system. A recent study, published in the journal Scientific Reports, has investigated the mismatch between students’ chronotype and their class timing, subsequently correlating this with decreased academic performance. Researchers Benjamin Smarr and Aaron Schirmer analyzed 2 years’ worth of online activity profiles for nearly 15 000 students at Northeastern Illinois University, sorting them into “morning larks,” “daytime finches” and “night owls,” based on their activity on free, non-class days. Their analysis revealed that 60% of students experienced social jet lag of more than 30 minutes; the extent of this jet lag correlating strongly with lower grade point averages. Although this mismatch was evident across all chronotypes, night owls were affected the worst; these individuals were the least phase-aligned with their class schedules and displayed performance deficits at all times of day. This work highlights the importance of circadian stability in personal academic achievement, moreover, it advocates for greater consistency in class scheduling by academic institutions.
Read more here:
Science Daily
https://www.sciencedaily.com/releases/2018/03/180329190847.htm
Education Week
http://blogs.edweek.org/edweek/inside-school-research/2018/03/grades_suffer_when_class_time.html
Futurity
https://www.futurity.org/social-jet-lag-schedule-college-students-1718712/
Berkeley News
http://news.berkeley.edu/2018/03/29/social-jetlag/
Original Article
https://www.nature.com/articles/s41598-018-23044-8
Why resetting the clock gets harder with age
by: D.Duglan | Mar 2018
The rhythmic outputs of the circadian clock are dynamic over a lifetime. Sleep-wake cycles can change dramatically as we age, which can lead to, or at least accelerate, declines in cognitive capacity and social function. A recent study, published in the journal Neurobiology of Aging, has now demonstrated how older age results in a reduced ability of the central clock in the brain (the suprachiasmatic nucleus – SCN) to be reset by light, a process known as photoentrainment. Dr. Gurprit Lall and colleagues compared the activity cycles of young (1-2 months) and old (14-18 months) mice after exposure to varying light intensities. Under all photic conditions, younger mice showed a greater behavioral phase shift upon light exposure, indicative of a more robust circadian response. These behavioral differences are unlikely due simply to age-related changes in retinal function, since both old and young mice displayed identical degrees of pupil constriction in response to bright light. Instead, the researchers ascribe this decline to altered expression of specific glutamate receptors (NMDA), which play a major role in the transduction of light inputs to the SCN and thus the entrainment of the circadian system. Older mice exhibited dampened expression of a key subunit of the NMDA receptor in the SCN, moreover, pharmacological inhibition of this subunit only reduced the resetting effects of light in young mice. Overall, the study demonstrates how the SCN may undergo a structural reconfiguration with age, leading to impaired synchronization of the circadian clock with the external environment. This glutamatergic signaling cascade may represent a novel therapeutic target for future treatments aimed at ameliorating circadian misalignment in elderly populations.
Read more here:
Science Daily
https://www.sciencedaily.com/releases/2018/03/180327102829.htm
Medical Daily
https://www.medicaldaily.com/why-disrupted-sleep-consequence-growing-older-423280
Original Article
http://www.neurobiologyofaging.org/article/S0197-4580(18)30056-3/fulltext
Time Flies across the Blood-Brain Barrier
by: D.Duglan | Mar 2018
The microvessels that comprise the blood-brain barrier (BBB) are crucial for proper neuronal function and help protect the brain from pathogens, toxins and inflammation. However, its restrictive nature also presents challenges for the delivery and efficacy of therapeutic drugs targeted towards the central nervous system. A new study from the laboratory of Amita Sehgal has now revealed that in fruit flies ( Drosophila Melanogaster) there is a specific molecular clock in the blood-brain barrier, which regulates the permeability of this barrier throughout the day. Researchers initially injected fluorescent dye into the thorax of flies and visualized its passage across the BBB, observing that its accumulation in the brain was greater in the evening compared to the daytime. To explore this effect in the context of neuromodulatory drugs, the team mechanically induced seizures in a strain of epileptic flies and subsequently tested the efficacy of the anti-seizure drug phenytoin. Consistent with observations of the fluorescent dye, they found that the speed of recovery from seizures was faster at night. Furthermore, this time-of-day effect could be abolished in mutant flies that possessed a disrupted molecular clock exclusively in a layer of the BBB. Mechanistically, this clock appears to have rhythmic control over the level of magnesium ions between the different cell layers, which in turn alters the activity of efflux transporters. At night, exposure of the transporters to lower concentrations of magnesium reduces their activity, preventing efflux and allowing for accumulation of compounds in the brain. These findings, published in the journal Cell, are now being applied to mice and human cell culture models; if this mechanism translates to mammals it could have serious implications for optimal drug regimens in patients with neurological disease.
Read more here:
Science Daily
https://www.sciencedaily.com/releases/2018/03/180309125205.htm
The Scientist
https://www.the-scientist.com/?articles.view/articleNo/52028/title/Fly-s-Blood-Brain-Barrier-Has-Circadian-Rhythms/
The Wire
https://thewire.in/science/a-flys-blood-brain-barrier-is-more-permeable-in-the-evening
Genetic Engineering and Biotechnology News
https://www.genengnews.com/gen-news-highlights/circadian-clock-in-bloodbrain-barrier-may-decide-best-drug-dosing-times/81255576
Original Article
http://www.cell.com/cell/fulltext/S0092-8674(18)30161-2
Irregular Shift Work, Irregular Blood Sugar
by: D.Duglan | Mar 2018
It has been estimated that 10% of the workforce in Western countries performs some type of night shift work, which can disrupt normal biological rhythms and has been associated with the risk of cardiovascular disease, diabetes and cancer. A recent study, published in the journal Diabetes Care, has now built upon these earlier findings, revealing that those individuals who worked irregular or rotating shifts had a 44% higher relative risk of type 2 diabetes compared to day workers. Celine Vetter and colleagues analyzed UK Biobank data for more than 270 000 people, examining the relationship between the type, as well as frequency of shift work, and disease risk. The researchers observed a dose-response effect for frequency, whereby the likelihood of having type 2 diabetes rose with increasing numbers of night shifts worked per month. Interestingly however, those individuals who worked permanent night shifts did not exhibit any increase in risk, which could suggest a long-term adaptation to this consistent schedule, although it may also be a product of other healthier lifestyle habits observed in this group. Another novel finding is that the negative effects of shift work on type 2 diabetes risk were present regardless of any genetic predispositions, with no observable interaction between genetic risk score and shift work exposure. Overall, the research highlights the potential metabolic costs of inconsistent work-life schedules that are incongruent with our biology. This is a pertinent subject for emergency service workers such as firefighters, who have recently teamed up with UCSD and Satchin Panda's Lab at the Salk Institute, in the hopes of ameliorating the deleterious effects of shift work with a circadian-based nutritional intervention.
Read more here:
ScienceDaily
https://www.sciencedaily.com/releases/2018/02/180212121228.htm
Sleep Review
http://www.sleepreviewmag.com/2018/02/frequency-shift-work-genetics-contribute-likelihood-type-2-diabetes/
Original Article
http://care.diabetesjournals.org/content/early/2018/01/31/dc17-1933
EurekAlert (SD Fire-Rescue collaborate with UCSD and Salk)
https://www.eurekalert.org/pub_releases/2018-02/si-sa021318.php
Circadian disruption as an early warning sign of Alzheimer’s
by: D.Duglan | Feb 2018
Poor sleep and perturbed daily activity patterns have been described extensively in patients that exhibit definitive neurodegenerative disease. However, until now, it has not been clear whether abnormal circadian rhythms exist in individuals with markers of preclinical Alzheimer’s, who otherwise display no cognitive symptoms. A recent study published in JAMA Neurology addressed precisely this question; Dr. Eric Musiek and colleagues studied wrist actigraphy data from 189 participants, in conjunction with the results of PET imaging and CSF sampling, which serve as biomarkers of amyloid plaque pathology. Those individuals who tested positive for amyloid deposition displayed significantly more circadian fragmentation, reflecting greater daytime sleep and nighttime wake. In the subset of individuals who tested negative for amyloid pathology, increased age was also associated with this rest-activity fragmentation. This work suggests that both normal aging and Alzheimer’s disease could separately drive circadian disruption, and it raises the question of whether each biological state could act through the same internal clock mechanism. While the direction of causality between disturbed sleep and Alzheimer’s onset has yet to be established, this research highlights the utility of the former as an early biomarker, which could hopefully be used in combination with other future diagnostic tools – perhaps a simple blood test.
Read more here:
Science Daily
https://www.sciencedaily.com/releases/2018/01/180129150033.htm
LA Times
http://www.latimes.com/science/sciencenow/la-sci-sn-alzheimers-circardian-rhythm-20180129-story.html
Futurity
http://www.futurity.org/circadian-rhythm-disruptions-alzheimers-1669212/
Sleep Review
http://www.sleepreviewmag.com/2018/01/body-clock-disruptions-occur-years-memory-loss-alzheimers/?ref=cl-title
Original Article
https://jamanetwork.com/journals/jamaneurology/article-abstract/2670749?redirect=true
Scientific American (Blood Test for Alzheimer’s)
https://www.scientificamerican.com/article/a-big-step-toward-a-blood-test-for-alzheimers/
Plant circadian clock coordinates stem growth at dawn
by: D.Duglan | Jan 2018
The responsiveness of plants to their photoperiod is finely integrated with their internal clock to direct growth, development and reproduction. The entrainment of their circadian oscillator by sunlight is largely mediated by the phytochrome-interacting factors (PIFs), a group of transcription factors that normally accumulate during the night phase to stimulate stem growth. Now, a new study published in the journal Current Biology has elucidated this mechanism further, highlighting the molecular components responsible for the specific timing of stem elongation in the plant Arabidopsis thaliana. Prof. Elena Monte and colleagues performed a detailed analysis of DNA-binding sites in Arabidopsis seedlings, demonstrating that specific DNA motifs interact with both PIFs and a repressive family of clock proteins called PRRs. They observed how this PIF-PRR protein interaction influenced the expression of a downstream growth factor, CDF5, and subsequently the daily timing of stem growth. Between the hours of morning and dusk, CDF5 expression was repressed by the sequential activity of different PRRs, thereby inhibiting growth. Throughout the night the process was reversed; PRR levels declined and PIFs accumulated, reaching a peak towards dawn and promoting stem growth via CDF5 induction. This work suggests an antagonistic model of growth-related gene regulation; moreover, it expands our understanding of the transcription-translation feedback loops that govern the rhythmic gating of plant physiology.
Read more here:
Phys.org
https://phys.org/news/2018-01-circadian-clock-pace-growth.html
News-Medical
https://www.news-medical.net/news/20180115/Circadian-clock-proteins-set-the-pace-of-plant-growth.aspx
Original article
http://www.cell.com/current-biology/fulltext/S0960-9822(17)31654-8
Time Heals All Wounds
by: A.Kriebs | Dec 2017
Fibroblasts are connective tissue cells that, among other functions, are crucial for wound healing. At the injured site, fibroblast migration, proliferation, and secretion of extracellular matrix proteins initiates the growth of new tissue. Fibroblasts are also a well-established circadian model system and synchronized cultures display robust rhythms in vitro. An analysis of rhythmically expressed proteins in these cells, performed by the O’Neill laboratory of the MRC Laboratory of Molecular Biology in Cambridge, has now found that the abundance of proteins involved in actin polymerization fluctuates with 24-hour periodicity.
The researchers asked whether circadian actin polymerization, driven by cell-intrinsic clocks, affects wound-oriented cell polarization, cell migration, and ultimately wound closure. In fact, the authors observed a striking time-of-wounding effect on the efficiency of wound healing both in cultured cells as well as in mouse skin samples. Injuries inflicted 24 hours after synchronization ( in vitro) or during the active phase ( in vivo) closed much more quickly compared to injuries sustained 32 hours after synchronization or during the inactive phase. This differential effect depended on functioning actin polymerization and was sustained for several days post wounding.
In further analysis of data from the International Burn Injury Database, the authors observed that burns sustained during the day time healed about twice as fast compared to burn injuries that occurred at night. This research has potential clinical relevance and indicates that patients might recover faster if surgeries are performed in sync with individual biological timing.
Read more here:
Chemical & Engineering News:
https://cen.acs.org/articles/95/i45/Circadian-rhythm-affects-wound-healing.html
BBC News:
http://www.bbc.com/news/health-41918368
Science:
http://www.sciencemag.org/news/2017/11/daytime-wounds-heal-more-quickly-those-suffered-night
Original article:
http://stm.sciencemag.org/content/9/415/eaal2774.short
Clocks That Run Faster with Eight Legs
by: D.Duglan | Dec 2017
The inability of an organism to entrain its circadian rhythm to the Earth’s 24-hour day is typically recognized as disadvantageous; lab animal mutants display reduced lifespan, while epidemiological reports in humans associate circadian disruption with increased risk of depression, cardiometabolic disease and cancer. However, this broad notion has just been challenged by a study of behavioral rhythms in the trashline orb-weaving spider, which were presented by lead author Darrell Moore at the recent Society for Neuroscience conference. This work, published in the Journal of Arachnology, demonstrated that these spiders have extremely short circadian cycles of between 17 and 19 hours, the shortest ever observed. Moore and colleagues caught several species of spider from the wild and measured their internal free-running period in constant darkness. While the spiders had a movement cycle of approximately 18.5 hours under these conditions, upon exposure to light the spiders reset their circadian clock by 6 hours the following day, seemingly without any noticeable jet-lag.
In terms of their natural daily activity, trashline orb-weavers remain motionless and camouflaged in their webs for most of the day, only becoming active in the remaining dark hours before sunrise. It is hypothesized that this accelerated internal clock allows them to avoid potential predators that become active after dawn. Interestingly, the authors note that unlike locomotor activity, the proclivity for web-building does not follow the same robust periodicity under constant darkness, suggesting that this behavior may at least be driven partly by the environmental factors. The molecular mechanism underlying this spider’s truncated circadian cycle remains unclear; undoubtedly now an area for further investigation. This study should also remind circadian biologists of the potential diversity of rhythms in other wild animals, and not merely those of model organisms maintained in a lab setting.
Read more here:
Scientific American
https://www.scientificamerican.com/article/meet-the-spiders-that-completely-defy-what-we-know-as-jet-lag/
New Scientist
https://www.newscientist.com/article/2153407-spiders-reset-body-clocks-to-avoid-5-hour-jet-lag-every-day/
Original Article
http://www.bioone.org/doi/abs/10.1636/JoA-S-16-014.1
Circadian Clock Passes the Sniff Test
by: D.Duglan | Nov 2017
While there is increasing appreciation for the role of tissue-specific clocks, recent work has now identified circadian oscillations in one of the major elements of our sensory perception: our sense of smell.
An exploratory study conducted by researchers at Brown University has revealed that odor detection sensitivity in adolescent teenagers varies throughout an individual’s circadian phase. Prof. Mary Carskadon and colleagues admitted 37 subjects to a controlled laboratory, where they underwent a week of 28-hour days, known as a “forced desynchrony” protocol. Unable to entrain to this 28-hour day, the method allows researchers to measure the outputs of free-running human oscillators; each subject’s circadian time was assessed by measuring melatonin levels.
Smell sensitivity to a chemical odor (rose-smelling) was then tested 6 times during the wake hours throughout each 28-hour cycle. The researchers found that on average, peak odor sensitivity in the teenagers occurred shortly after the onset of melatonin production, which would correspond to approximately 9pm. While there was significant variability between individuals’ timing of peak sensitivity, none of the subjects displayed peaks between the approximate hours of 2am and 10am.
This work has interesting implications for both our evolutionary origins and our modern lives. An improved sense of smell towards the end of the day may have been advantageous for the detection of predators, when darkness would impair visual acuity. The primary feeding period for our hunter-gatherer ancestors also likely occurred during the evening, therefore heightened olfactory sensing may have aided detection of toxins and improved flavor perception.
In a practical sense, this study may be useful for clinicians who use olfactory diagnostic tests, the results of which could vary between early morning and late afternoon measurements. It also builds on earlier work demonstrating that during sleep our odor detection ability is blunted, underscoring the importance of auditory fire alarms. This research was published in Chemical Senses and is part of a larger ongoing project investigating the relationship between sense of smell and dietary habits in teenagers.
Further reading:
Science Daily
https://www.sciencedaily.com/releases/2017/10/171026103130.htm
New York Times
https://www.nytimes.com/2017/11/08/science/nose-smell-circadian-rhythm.html
Brown Daily Herald
http://www.browndailyherald.com/2017/11/07/circadian-rhythms-linked-smell-sensitivity/
Original Article
https://academic.oup.com/chemse/article-abstract/doi/10.1093/chemse/bjx067/4555280?redirectedFrom=fulltext
Clocks at the Heart of the Matter
by: A.Kriebs | Nov 2017
Healthy human physiology is robustly rhythmic, as is the timing of onset of adverse health events, including myocardial infarction, sudden cardiac death, and stroke. These observations suggest that there is an optimal time-of-day for therapeutic treatments. Finding ways to harness circadian timing to make medical interventions more effective and safer (also known as chronotherapy) has been the subject of much study, promising easy and cost effective solutions.
Now a new study published in The Lancet shows that patients stand to benefit from the simple act of scheduling their heart surgery for the afternoon rather than the morning. Patients undergoing on-pump heart surgery will experience reoxygenation injuries of the heart tissue which increase the risk for adverse cardiac events, such as myocardial infarction and acute heart failure.
To improve clinical outcomes the authors studied the occurrence of adverse events after aortic valve replacement in patients with surgery in the morning or the afternoon and found that the afternoon group fared significantly better. Ex vivo study of human biopsy samples indicated that myocardial tissue taken in the afternoon was better adapted to cope with a hypoxia-reoxygenation challenge. This coincided with differences in REV-ERBα and BMAL1 expression. Intriguingly, chemical or genetic ablation of Rev-erbα function in mouse hearts resulted in increased hypoxia-reoxygenation tolerance, implicating cardiomyocyte clock transcriptional regulation as at least partly responsible for the effect and raising the possibility of chemical intervention targeting REV-ERBα to improve patient outcomes.
Thus this study presents compelling options to improve outcomes of patients undergoing this type of surgery.
Read more here:
Scientific American
https://www.scientificamerican.com/article/why-heart-surgery-may-be-better-in-the-afternoon/
New York Times
https://www.nytimes.com/2017/11/01/well/live/heart-surgery-may-be-safer-in-afternoon-than-in-morning.html?_r=0
CBS News
https://www.cbsnews.com/news/heart-surgery-safer-time-of-day-afternoon/
Original article
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32132-3/fulltext?elsca1=tlpr
Chronobiologists’ Circadian Clocks Skip a Beat as Nobel Prize is Announced
by: A.Kriebs and D.Duglan | Oct 2017
Ubiquitously, circadian biology literature defines the eukaryotic circadian clock as the mechanism that generates self-sustained transcription-translation feedback loops and thus drives rhythmic expression of genes with 24-hour periodicity. Now, the scientists whose work throughout the 1980s and 1990s laid the foundation for our understanding of the biological clockwork, Jeffrey Hall, Michael Rosbash and Michael Young, have been awarded the Nobel prize for Physiology or Medicine.
Using the model organism Drosophila melanogaster, the scientists studied the period gene, which had been shown to be required for normal fly biological rhythms, including circadian patterns of eclosion and locomotor activity, as well as short-term male courtship song oscillations. In 1984 Jeffrey Hall and Michael Rosbash, collaborators at Brandeis University, as well as Michael Young at Rockefeller University, independently succeeded in isolating the period gene. Subsequently, Hall and Rosbash demonstrated that the abundance of the period gene product, the PER protein, fluctuates with 24-hour periodicity, peaking during the night and hardly detectable during the day. This oscillation persisted in constant darkness. Subsequent work by the three scientists was key to identifying the molecular mechanism that generated these oscillations. Observing that mutations in the period gene affected the periodicity of its mRNA rhythms, Hall and Rosbash proposed that the PER protein itself was involved in a feedback loop regulating its own expression. In fact, work by Young led to the identification and functional characterization of an additional clock component, timeless. He showed that TIM , PER’s heterodimer partner, facilitates PER translocation into the nucleus where the complex represses period expression. Young also identified double-time. The protein kinase DOUBLE-TIME destabilizes PER, thus explaining how PER degrades during the day and how the cycle is able to renew. Homologs of Drosophila clock protein components are present in other animals and function by the same principles, therefore their work created a molecular understanding of the gears that govern circadian rhythms in other species, including humans.
These internal rhythms coordinate the timing of essential aspects of our physiology and behavior, such as the sleep-wake cycle, metabolism and immune function, as well cardiovascular, endocrine and reproductive health. This intrinsic ability to match physiological processes to fundamental environmental cues over the 24 hour day is central to an organism’s evolutionary success. However, the presence of an entrainable circadian clock can be a double-edged sword; namely in the face of modern changes to our environment. In a world of rotational shift work, jet lag and inappropriate lighting and feeding schedules, a discordance can arise between our biology and our contemporary lifestyles. These circadian stressors are now increasingly associated with the development of cardiovascular and metabolic disease, as well as the risk of cancer. An optimistic future of preventing and reversing these serious health conditions will likely involve further resolution of the molecular clock, which will no doubt be inspired by the celebrated work of these three circadian pioneers.
Michael Young, who is Vice President for Academic Affairs and Richard and Jeanne Fisher Professor in the Laboratory of Genetics at The Rockefeller University, also serves on the CCB’s external advisory board. The Young laboratory currently studies the genetic underpinnings of homeostatic sleep regulation in Drosophila, as well as the activity of the human circadian clock in cells derived from patients with sleep or depressive disorders. Most recently, this work led to the identification of a mutation in CRY1 which causes familial delayed sleep phase disorder.
Read more here:
https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html
(Also follow this link to take a peek at the key publications that document these discoveries.)
https://www.nytimes.com/2017/10/02/health/nobel-prize-medicine.html?mcubz=0&_r=0
https://www.washingtonpost.com/world/americans-win-nobel-medicine-prize-for-circadian-rhythm-work/2017/10/02/fc8fff50-a756-11e7-9a98-07140d2eed02_story.html
http://www.latimes.com/science/sciencenow/la-sci-sn-nobel-prize-medicine-20171002-story.html
https://www.nature.com/news/medicine-nobel-awarded-for-work-on-circadian-clocks-1.22736
The Scientist interviews with Micheal Young and Michael Rosbash:
http://www.the-scientist.com/?articles.view/articleNo/50555/title/Q-A-with-Michael-Young--Nobel-Laureate/
Leishmania Takes Advantage of Immune Cell Rhythms
by: A.Kriebs | Oct 2017
Immune function varies with the time-of-day. Circadian clocks temporally coordinate immune cell localization, cytokine and chemokine expression, as well as other processes to help organisms cope with the risk of pathogenic infection. The chances of encountering air and food borne pathogens are heightened during the active phase. In fact, studies in mice have shown that the animals are most susceptible to viral and bacterial infections during the early inactive period, when exposure to pathogens is anticipated to be low.
Now, in a new study from the lab of Nicolas Cermakian at McGill University, Silke Kiessling and her colleagues explore the time-of-day dependence of Leishmania infection - a parasite that is transmitted through female sandfly bites and resides in the host’s neutrophils and macrophages. The researchers infected mice with the parasite at different times-of-day. They observed that parasitic load was lowest when the infection took place at ZT3 (inactive period) and highest when it occurred at ZT15 (active period). To determine the cause, the team looked at the host cells targeted by the parasite and found that parasitic insult at ZT15 more strongly induced the expression of chemoattractants and resulted in increased neutrophil recruitment to the site of infection thus enhancing the efficiency of parasitic invasion. These effects were abolished when the circadian clock was ablated in bone marrow cells by knocking-out the Bmal1 gene.
This study indicates that the time of highest Leishmania infectivity corresponds to the natural time of sandfly biting behavior which occurs at dusk and continues into the night. While it is not known how this research translates to humans it raises the possibility that the Leishmania parasite benefits from the circadian gating of the immune response.
Read more here:
McGill Newsroom:
http://www.mcgill.ca/newsroom/channels/news/meeting-microbe-morning-or-evening-it-all-same-270162
Infectious Diseases Hub:
https://www.id-hub.com/2017/09/11/time-day-influence-leishmania-infection/
McGill Tribune:
http://www.mcgilltribune.com/sci-tech/when-is-the-best-time-to-get-sick-09182017/
Original article:
https://www.nature.com/articles/s41598-017-11297-8
Circadian clock and gut microbiome team up to control body fat
by: D.Duglan | Sep 2017
The make-up of our intestinal microbiota is ever-increasingly being linked to our overall metabolic health. Recent work by scientists at Southwestern Medical Center (Dallas) has revealed that the gut flora is dependent on the circadian transcription factor Nfil3 to influence body composition. The team, led by Prof. Lora Hooper, generated mice that lacked Nfil3 in intestinal epithelial cells, observing that these mice were protected against those deleterious effects of being placed on a Western-style diet; namely weight gain, hepatic fat deposition and insulin resistance. This was also replicated in other germ-free mice that completely lacked a microbiome, demonstrating the interdependence of Nfil3 and the gut flora to modulate body fat accumulation. Whilst Nfil3 has typically been associated with the circadian regulation of immune function, this latest research now defines a role for the protein in controlling lipid absorption across the intestinal lining. It remains to be seen whether this same molecular link might underlie the incidence of metabolic syndrome in humans that are subjected to circadian disruption.
Further reading:
Medical News Today
https://www.medicalnewstoday.com/articles/319390.php
Original Article
http://science.sciencemag.org/content/357/6354/912.full
Body Clocks Control Metabolic Health
by: A.Kriebs | Sep 2017
Circadian clocks are crucial for maintaining metabolic health. The brain clock regulates sleep and activity cycles, as well as the timing of other behaviors, like feeding, while clocks in peripheral tissues coordinate daily rhythms of physiology and metabolism. Clocks, for example in the liver and pancreas, regulate proper responses to food consumption. Evidence suggests that meal timing, not only calorie count, affects weight gain, as discussed in the FiveThirtyEight article linked to below.
To further dissect the mechanisms underlying health benefits through restriction of food intake the laboratories of Profs. Carla Greene and Joseph Takahashi developed an automated feeder system that allows precise control of the amount, duration and timing of food availability in animal studies. Applying this system to several commonly used feeding paradigms, like temporal restriction and caloric restriction, showed that calorically restricted mice lost weight only when fed during the night, the animal’s active period, not when fed during the day. The study also revealed that calorie restriction altered running wheel activity and that activity patterns varied over the course of the study, underlining the plasticity of feeding and activity behavior. The authors hope that their new feeder system will help scientists assess the respective contributions of reduced calorie count and timing of food intake to increased longevity observed with calorie restriction regiments.
Read more here:
FiveThirtyEight article:
https://fivethirtyeight.com/features/when-should-we-eat/
Original article:
http://www.sciencedirect.com/science/article/pii/S1550413117303492?via%3Dihub
UT Southwestern news release:
http://www.utsouthwestern.edu/newsroom/news-releases/year-2017/jul/lifespan-research-takahashi.html
Food Network:
http://blog.foodnetwork.com/healthyeats/2017/09/03/why-when-you-eat-may-be-as-important-as-what-you-eat/
What Sunscreen and Eating Time Have in Common
by: A.Kriebs | Sep 2017
Circadian clocks are present in virtually all tissues of the body to optimally regulate tissue specific functions, e.g. the skin circadian clock protects from UV-induced DNA damage, at least in part, by increasing the expression of DNA repair machinery during the day, when skin is exposed to sunlight.
Time-telling external stimuli that enable proper circadian synchronization to the environment include light and food availability. While light received through the eyes allows the master circadian clock in the brain to tell the time-of-day and synchronize peripheral circadian clocks, circadian oscillations, especially in metabolic organs such as the liver, can be shifted relative to brain-time through time-restricted feeding.
A new study from the laboratory of Prof. Bogi Andersen at the University of California, Irvine, now shows that the skin circadian oscillator is also sensitive to feeding time. Comparing circadian rhythms of gene expression in mice that received food at different times of the day or at night showed that skin circadian phase was shifted in response to feeding time. The authors also demonstrate that animals that feed at night, like they naturally would, are more sensitive to UVB-induced damage at night compared to the day. However, day-time feeding reverses the diurnal sensitivity to UVB-induced DNA damage. While it is unclear how these results translate to humans, this study reveals an unanticipated connection between the circadian timing cue, feeding time, and the skin circadian clock.
Read more here:
Original article:
http://www.sciencedirect.com/science/article/pii/S2211124717309889
UT Southwestern news release:
http://www.utsouthwestern.edu/newsroom/news-releases/year-2017/aug/eating-affects-skin-protection.html
Night Owl Genetics
by: A.Kriebs | Apr 2017
The recommendation: “Early to bed, and early to rise” is not for everyone. Preference for sleep timing, or chronotype, is determined by the circadian clock. Roughly, there are morning larks and night owls. Chronotype can determine compatibility with certain social schedules and extreme chronotypes can be very disruptive to the regular day-to-day. Recently, researchers at Rockefeller University discovered the genetic underpinnings of a slow circadian clock that caused delayed sleep phase disorder (DSPD). The study from the laboratory of Prof. Michael Young, a member of the CCB advisory board, lead by Dr. Alina Patke linked the disorder to a variant of the CRY1 gene, a component of the mammalian circadian clock. The resulting protein product was missing a small portion in the C-terminal tail. This shorter CRY1 turned out to be a more potent version of the full length form effectively slowing down circadian time. While there are currently no treatment options targeting CRY1 this finding is still highly relevant and could encourage development of the same since this gene variant is likely present in one out of 75 individuals.
Read more here:
CBC News
http://www.cbc.ca/news/technology/night-owl-gene-1.4069398
Live Science
https://www.livescience.com/58573-delayed-sleep-phase-disorder-linked-to-gene-mutation.html
Original article:
http://www.cell.com/cell/pdf/S0092-8674(17)30346-X.pdf
Dreams of Sounds that Enhance Memory
by: A.Kriebs | Mar 2017
Anecdotally, a good night’s sleep is one of the most frequently prescribed remedies. In fact, sleep is crucial for physical and mental well-being. Among other things, memories are solidified during sleep. As both sleep and memory change over the course of a lifetime, researchers are exploring the interconnection between sleep, memory, and aging. Scientists at Northwestern University Medical School focused on decreasing slow wave activity, a sleep stage associated with the ability to recall factual information and experiences, in adults 60 years and older. The team of CCB advisory board member Prof. Phyllis Zee reports that sound stimulation during certain parts of the slow wave activity improved test subjects’ performance in memory tests the next day. This exciting new finding could lead to easy, non-invasive interventions to prevent age-related memory decline.
Read more here:
WTTW (Chicago PBS):
http://chicagotonight.wttw.com/2017/03/08/study-waterfall-sounds-enhance-deep-sleep-memory-older-adults
Original article:
http://journal.frontiersin.org/article/10.3389/fnhum.2017.00109/full
The Sunflower Circadian Clock: A Head Turner
by: A.Kriebs | Feb 2017
Plants are often perceived as immobile. However, circadian biologists, dating back to the French scientist Jean-Jaques de Mairan in the 1700(s), knew that plants show daily rhythms of movement. More recently, in an elegant study, the team of Prof. Stacey Harmer from UC Davis, a CCB Associate member, showed that the east to west rotation of young sunflower plants over the course of the day is controlled by an internal circadian clock and helped the young flowers to grow bigger than their sibling plants whose movement was impeded. While young sunflowers rotated their heads to follow the sun, this behavior stopped in adult sunflowers, which faced perpetually east. Adult flowers have evolved to face the rising sun because the warmth helps them to attract pollinators. This study was published in the journal Science and featured in the Los Angles Times in August of 2016.
Read more here:
LA Times article:
http://www.latimes.com/science/sciencenow/la-sci-sn-sunflowers-direction-20160804-snap-story.html
Original article:
http://science.sciencemag.org/content/353/6299/587
Reset Your Circadian Clock by Going Camping
by: A.Kriebs | Feb 2017
The expression “to go to bed with the chickens” refers to a time when people’s sleep wake cycle was dictated by the natural day. In modern society this is no longer the case. We often stay up long after dusk, since we don’t have to rely on natural light to do our work. As a consequence our biological night, as defined by elevated levels of the sleep hormone melatonin, begins long after dark. Therefore, when it is time to rise in the morning melatonin levels may still be high, making getting out of bed a challenge. The team of Prof. Kenneth Wright from the University of Colorado, Boulder, reports that camping might help. Their unique study, published in the journal Current Biology and featured in this Los Angles Times article, shows that a weekend camping trip in the Rocky Mountains, away from electric lighting, was sufficient to shift the melatonin profile of campers more than an hour earlier compared with the control group that stayed home. Additionally, the researchers showed that the melatonin profiles mirror seasonal changes in day length. Therefore, maximizing light exposure during the day as well as minimizing it during the night is key to changing sleep patterns
Read more here:
LA Times article:
http://www.latimes.com/science/sciencenow/la-sci-sn-camping-better-sleep-20170202-story.html
Original article:
http://www.cell.com/current-biology/fulltext/S0960-9822(16)31522-6
