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Body clock researchers prevent liver cancer growth in mice -- ScienceDaily

The body's clock, called the circadian clock, is an intrinsic, 24-hour timekeeping system that operates in all cells of the body and regulates sleep, metabolism and other vital body functions. "We were able to inhibit the growth of liver cancer in a mouse model by manipulating the circadian clock at the cellular level," said Kristin Eckel-Mahan, Ph.D., the study's senior author and an assistant professor with the Center for Metabolic and Degenerative Diseases at McGovern Medical School at UTHealth.

Mouse and human skin cells produce melanin on a 48-hour cycle -- ScienceDaily

. They observed that a 48-hour cycle of exposure resulted in the darkest coloration of the cells while minimizing the effects of stress, even when they controlled for total dosage of exposure. "The results were so surprising," says Levy. "We expected daily synchronization of the cell's protective cycles." Levy and her colleagues, including co-senior author and systems biologist Shai Shen-Orr and his PhD student Avelet Alpert of the Technion -- Israel Institute of Technology, observed that MITF (microphthalmia-associated transcription factor) seemed to play a role in synchronizing the protective cycles. MITF was previously shown to control production of melanin and its spread to surrounding skin cells. They found that upon one ultraviolet exposure, MITF expression fluctuates every 48 hours. Another exposure 24 hours later seemed to disrupt this expression pattern.

Antipsychotics ineffective for treating ICU delirium -- ScienceDaily

he large, multi-site MIND USA (Modifying the INcidence of Delirium) study sought to answer whether typical and atypical antipsychotics -- haloperidol or ziprasidone -- affected delirium, survival, length of stay or safety. "We found, after extensive investigation with medical centers all over the country, that the patients who get these potentially dangerous drugs are not experiencing any improvements whatsoever in delirium, coma, length of stay or survival," said senior author by E. Wesley Ely, MD, MPH, professor of Medicine at Vanderbilt University School of Medicine, associate director of Research for the VA Geriatric Research Education Clinical Center, and co-director of the CIBS (Critical Illness, Brain dysfunction, and Survivorship) Center at Vanderbilt University Medical Center. Researchers screened nearly 21,000 patients at 16 U.S. medical centers. Of the 1,183 patients on mechanical ventilation or in shock, 566 became delirious and were randomized into groups receiving either intravenous haloperidol, ziprasidone or placebo (saline). The investigators found no significant difference in duration of delirium or coma among participants on haloperidol or ziprasidone compared to placebo.

Man's Bipolar Mood Cycles Linked to the Moon | American Council on Science and Health

The author observed the behavior of a 51-year-old man with bipolar disorder. Patients with bipolar disorder experience manic-depressive cycles. The depressive cycles resemble those of patients suffering from severe depression, while during manic cycles, patients are hyperactive. Sleep patterns are abnormal, with patients sleeping too much during depressive episodes and not enough during manic episodes. In a sort of vicious cycle, disturbances in sleep pattern appear to be both a cause and effect of manic-depressive episodes.

How do muscles know what time it is? -- ScienceDaily

In collaboration with Italian and Austrian colleagues (from the Venetian Institute of Molecular Medicine and the Universities of Padua, Graz, and Trieste) the researchers identified certain processes that are switched on at night by the regulators of the internal clock: "They include, for example, fat storage, glucose metabolism and insulin sensitivity," explains Henriette Uhlenhaut. At the same time, opposing processes such as fatty acid oxidation and protein breakdown are throttled down, according the authors. These patterns are especially pronounced in the hours before awakening and are thought to prepare the muscles for the day ahead. In the final step, the scientists investigated possible ways to intervene in these processes. To this end, they examined mice lacking these master regulators. Without a circadian clock, the animals were leaner, with less fat and more muscle mass. "Taken together, our work has revealed an entire metabolic network at multiple levels," Uhlenhaut explains. "Another biologically exciting finding is that, contrary to expectations, the key regulator is not centrally located in the brain, but is in fact the internal clock of the muscle cells themselves." In the long term, the authors will investigate the mechanisms also in humans and try to find a way for therapeutic interventions. Their hope is that it might be possible to counteract insulin resistance in type 2 diabetes or to stimulate energy use to combat obesity.

A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Health Benefits. - PubMed - NCBI

The daily intake duration (95% interval) exceeded 14.75 hr for half of the cohort. When overweight individuals with >14 hr eating duration ate for only 10-11 hr daily for 16 weeks assisted by a data visualization (raster plot of dietary intake pattern, "feedogram") that we developed, they reduced body weight, reported being energetic, and improved sleep. Benefits persisted for a year.

Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges - ScienceDirect

Here we tested TRF in mice under diverse nutritional challenges. We show that TRF attenuated metabolic diseases arising from a variety of obesogenic diets, and that benefits were proportional to the fasting duration. Furthermore, protective effects were maintained even when TRF was temporarily interrupted by ad libitum access to food during weekends, a regimen particularly relevant to human lifestyle. Finally, TRF stabilized and reversed the progression of metabolic diseases in mice with preexisting obesity and type II diabetes. We establish clinically relevant parameters of TRF for preventing and treating obesity and metabolic disorders, including type II diabetes, hepatic steatosis, and hypercholesterolemia.

Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet - ScienceDirect

To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

Strategic fasting improves race times

In this particular study, both groups actually consumed the same amount of carbohydrates, but the sleep-low group ate all of theirs between their morning and afternoon sessions while the control group also had carbs after their second workout. Both groups completed a test triathlon to assess their fitness and then a second one three weeks later to determine the effectiveness of the training method. The sleep-low group had improved their running times on the 10-km segment by an average of 75 seconds while the control group showed no improvement. The sleep low athletes also lost about 3 pounds of body fat while the control group stayed the same.

Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males

After 8 weeks, the 2 Way ANOVA (Time * Diet interaction) showed a decrease in fat mass in TRF compared to ND (p = 0.0448), while fat-free mass, muscle area of the arm and thigh, and maximal strength were maintained in both groups. Testosterone and insulin-like growth factor 1 decreased significantly in TRF, with no changes in ND (p = 0.0476; p = 0.0397). Adiponectin increased (p = 0.0000) in TRF while total leptin decreased (p = 0.0001), although not when adjusted for fat mass. Triiodothyronine decreased in TRF, but no significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides. Resting energy expenditure was unchanged, but a significant decrease in respiratory ratio was observed in the TRF group.

How Shift Work Disrupts Metabolism - Neuroscience News

They found that, following the night shift schedule, 24-hour rhythms in metabolites related to the digestive system had shifted by a full 12 hours, even though the master biological clock in participants’ brains had only moved by about 2 hours. Biological clocks in digestive organs “No one knew that biological clocks in people’s digestive organs are so profoundly and quickly changed by shift work schedules, even though the brain’s master clock barely adapts to such schedules,” said co-senior author Hans Van Dongen, director of the WSU Sleep and Performance Research Center and a professor in the Elson S. Floyd College of Medicine. “As a result, some biological signals in shift workers’ bodies are saying it’s day while other signals are saying it’s night, which causes disruption of metabolism.”

Sensitivity of the circadian system to evening bright light in preschool‐age children

We found robust melatonin suppression (87.6 ± 10.0%) in response to the bright light stimulus. Melatonin levels remained attenuated for 50‐min after termination of the light stimulus (P < 0.008). Furthermore, melatonin levels did not return to 50% of those observed in the dim light condition 50‐min after the light exposure for 7/10 children.

Risk of Burnout Can Be Estimated by Analyzing Saliva Samples - Neuroscience News

According to the researchers, compared with the previously used early-morning samples – taken three times after waking at fifteen-minute intervals – the midday and evening saliva samples also provided a much better and more reliable result: “Our current data indicate that people at risk of burnout can be identified from a single saliva sample with almost 100% accuracy, whereas the multiple early-morning sampling involved more laborious methods and produced a much larger range of variation.” Reliable analysis is now possible just four hours after providing the sample and this method even produced better results than analysing stress-related blood parameters. “We will use these results to further reinforce our efforts to prevent stress-related illnesses in collaboration with the stress clinic of the KFA Health and Prevention Center.

Early birds less prone to depression: Largest study yet links chronotype to mental health -- ScienceDaily

In 2009, all the participants included in the study were free of depression. When asked about their sleep patterns, 37 percent described themselves as early types, 53 percent described themselves as intermediate types, and 10 percent described themselves as evening types. The women were followed for four years to see who developed depression. Depression risk factors like body weight, physical activity, chronic disease, sleep duration, or night shift work were also assessed. The researchers found that late chronotypes, or night owls, are less likely to be married, more likely to live alone and be smokers, and more likely to have erratic sleep patterns. After accounting for these factors, they found that early risers still had a 12 -- 27 percent lower risk of being depressed than intermediate types. Late types had a 6 percent higher risk than intermediate types ( this modest increase was not statistically significant.) "This tells us that there might be an effect of chronotype on depression risk that is not driven by environmental and lifestyle factors," said Vetter.

Color-Changing LEDs Could Reset the Circadian Rhythm - The Atlantic

Hints of positive impacts have emerged in Texas, too, where tunable LED systems have been installed in some elementary and middle-school classrooms in Carrollton, a northern suburb of Dallas. A September DOE report on the Carrollton systems suggested that the tunable LED system had improved the overall learning environment—though the DOE noted that empirically measuring the effects of the circadian lights was beyond the scope of the project. Back in Washington, entire schools—including two Renton high schools and a brand new middle school—now have circadian lighting, and initial data out of Lindbergh High School seemed to echo the findings in Texas: The school reported a double-digit rise in SAT test scores following installation of the tunable LEDs.

Color-Changing LEDs Could Reset the Circadian Rhythm - The Atlantic

In much the same way as the ear allows us to both hear and stay balanced, the eye’s rods and cones supply us with vision while these novel intrinsic photosensitive retinal ganglion cells, or ipRGCs, perform a separate function: They sense the quality and quantity of light, with input from the rods and cones, and send that information to a master circadian clock in the brain. That clock then conducts a symphony of cellular timepieces throughout the body, ensuring they all “rise and fall with appropriate relationships to the others,” explains Berson.

Chronobiological therapy for mood disorders: Expert Review of Neurotherapeutics: Vol 11, No 7

Alteration of the sleep–wake cycle and of the sleep structure are core symptoms of a major depressive episode, and occur both in course of bipolar disorder and of major depressive disorder. Many other circadian rhythms, such as the daily profiles of body temperature, cortisol, thyrotropin, prolactin, growth hormone, melatonin and excretion of various metabolites in the urine, are disrupted in depressed patients, both unipolar and bipolar individuals. These disrupted rhythms seem to return to normality with patient recovery. Research on circadian rhythms and sleep have led to the definition of nonpharmacological therapies of mood disorder that can be used in everyday practice. These strategies, named chronotherapeutics, are based on controlled exposures to environmental stimuli that act on biological rhythms, and demonstrate good efficacy in the treatment of illness episodes.

Geographic variation in the prevalence of attention-deficit/hyperactivity disorder: the sunny perspective. - PubMed - NCBI

The preventative effect of high SI might be related to an improvement of circadian clock disturbances, which have recently been associated with ADHD. These findings likely apply to a substantial subgroup of ADHD patients and have major implications in our understanding of the etiology and possibly prevention of ADHD by medical professionals, schools, parents, and manufacturers of mobile devices.

Tick tock: Study links body clock to mood disorders |

or the new study, an international team led by University of Glasgow psychologist Laura Lyall analysed data -- taken from the UK Biobank, one of the most complete long-term health surveys ever done -- on 91,105 people aged 37 to 73. The volunteers wore accelerometers that measured patterns of rest and activity and had this record compared to their mental history, also taken from the UK Biobank. Individuals with a history of disrupting their body's natural rhythm -- working night shifts, for example, or suffering repeated jetlag -- also tended to have a higher lifetime risk of mood disorders, feelings of unhappiness, and cognitive problems, the researchers found.

Effects of night-time light on internal body clock -- ScienceDaily

Melatonin suppression and circadian phase resetting are often correlated such that high levels of melatonin suppression can be associated with large shifts of the body clock. This association between the two responses has often been assumed to represent a functional relationship, resulting in the acceptance that one could be used as a proxy measure for the other. Circadian phase resetting is more difficult to measure than melatonin suppression, meaning the latter has often been used to assess disruption to the body clock caused by light exposure at night. However, this research has found that the magnitude of the shift in internal body clock is functionally independent from melatonin suppression. This casts doubt on the use of melatonin suppression as a proxy for circadian phase resetting. This knowledge may shape future research designed to improve treatments for depression and shift work sleep disorder.

Brain activity linked to stress changes chemical codes: Findings may be relevant to other disorders, from autism to PTSD -- ScienceDaily

In the new findings, the researchers studied the change in neurotransmitter identity when rats, which are nocturnal, are exposed to long day lengths. This exposure led to elevated activity of paraventricular (PaVN) neurons in the hypothalamus and by consequence a loss in their expression of dopamine, a neurotransmitter that is linked with many aspects of normal behavior. When the researchers suppressed the elevation of activity that resulted from the long-day exposure, exclusively in the PaVN neurons, they blocked the transmitter switch that would have occurred under these normal light conditions.

Revisiting existing drugs finds molecules that control body clocks: Discovery of an anti-aging supplement that reduces jet lag in mice -- ScienceDaily

For most travellers, flying west (e.g. from Asia to Europe), which delays the circadian clock, does not cause too many health problems. On the other hand, flying east (e.g. from Asia to America), which fast-forwards the circadian clock, forces people to wake up earlier than usual and tends to cause severe jet lag symptoms, such as fatigue and insomnia. Therefore, Yoshimura and his group decided to investigate circadian period-shortening compounds that will fast-forward the circadian clock and relieve jet lag symptoms when travelling east. Among the 13 circadian period-shortening compounds that the group identified, the researchers focused on a steroid hormone, dehydroepiandrosterone (DHEA), which is commercially available as an anti-aging supplement in USA. In humans, DHEA is produced in the adrenal gland, gonads and brain, and is a precursor for testosterone and estrogen. DHEA is one of the most abundant circulating hormones in the blood stream, but its concentration usually decreases with age. This is why DHEA is sold as a supplement for anti-aging and for boosting metabolism. Further investigation showed that DHEA shortens the period of the circadian clock in cultured human cells in a dose dependent manner. The team found that DHEA speeds up the circadian rhythm in human cells, as well as in cultured cells and tissues of mice. As previous studies have demonstrated the safety of orally administering DHEA in mice, experiments were carried out to test whether DHEA had an effect on the circadian rhythm of mice.

Circadian system

Circadian clock research has been ongoing for many decades and has led to the discovery of molecular mechanisms controlling the circadian rhythm, which was awarded the 2017 Nobel Prize in Physiology or Medicine. Almost all of the cells in our body contain a circadian clock and are mainly controlled by a central circadian pacemaker, located in the hypothalamus of the brain. The circadian clocks contained in most tissues and cells are driven by transcriptional-translational feedback loops composed of circadian clock genes and proteins.

Circadian Clock That Controls Daily Aggression Rhythms Located - Neuroscience News

“The mice were more likely to be aggressive in the early evening around lights out, and least aggressive in the early morning, around lights on,” Saper said. “It looks like aggressiveness builds up in mice during the lights on period, and reaches a peak around the end of the light period.”

Three genes essential for cells to tell time -- ScienceDaily

"Many researchers in this field have long suspected oxidative stress and circadian rhythms are somehow connected because of the cycles of photosynthesis and DNA replication we see even in ancient organisms; photosynthesis requires sunlight and creates free radicals that could damage DNA, so cells postpone DNA replication and cell division until nighttime when photosynthesis has stopped. We are very excited about our results because we can approach the origin of the circadian clock by connecting oxidative stress and circadian regulation through the Ask genes," said Fukada.

Another way morning exercise resets your circadian rhythm?

In flies, temperature could be sensed directly by neurons in the brain or via nerve impulses from sensory organs in the body. To distinguish between the two, the investigators genetically manipulated or physically removed the sensory organs and found that the DN1p neurons no longer responded to changes in temperature. This meant that the clock interprets temperature signals from the body rather than sensing temperature changes directly. The circadian clock of larger animals and humans is also sensitive to changes in temperature, and because of their larger size, would require input from external sensory organs. The fact that, despite its small size, the fly clock also relies on temperature sensors outside the brain suggests that the findings of this study could have broad implications in the control of sleep in humans.