The long wait for a Nobel Prize to recognize these advancements is not unusual, said Dr. Brown, who has served on selection panels for other prestigious scientific awards. For instance, the discovery of the DNA structure by Drs.

James Watson, Francis Crick, and Maurice Wilkins garnered the honor nearly a decade later. Brown and Goldstein earned their Nobel 12 years after the cholesterol discovery.

Albert Einstein eventually won a Nobel, but not for his theory of relativity. Brown, acknowledging the work from other scientists who translated his research into cholesterol-lowering drugs.

He said he expects Dr. But CLOCK is already a great discovery, and the beauty of the discovery is the insight it gives us into how nature works. Brown is the W. Monty Moncrief Distinguished Chair in Cholesterol and Arteriosclerosis Research, the Paul J.

Thomas Chair in Medicine, and Professor of Molecular Genetics and Internal Medicine. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education.

The faculty of almost 2, is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments.

UT Southwestern physicians provide medical care in about 80 specialties to more than , hospitalized patients and oversee approximately 2. UT Southwestern Medical Center researchers have identified an experimental molecular compound that significantly improved survival among cellular models and mouse models of amyotrophic lateral sclerosis ALS , the fatal neurodegenerative disease.

A study of mutant models of fragile X syndrome FXS , a genetic disorder related to autism and intellectual disability, shows that activation of the cerebellum mitigates aberrant responses in sensory processing areas of the brain and improves neurodevelopmental behaviors.

An increased concentration of the hormone leptin in fat cells is believed to be responsible for weight gain associated with antipsychotic drugs. Site Navigation UT Southwestern Home Research Clinical Trials Core Facilities CTSA Program Postdoctoral Scholars Programs Research Support Research by Department Research Labs Scientific Discoveries Technology Development.

Centers and Institutes Advanced Imaging Research Center AIRC Cecil H. and Ida Green Comprehensive Center for Molecular, Computational, and Systems Biology Cecil H. and Ida Green Center for Reproductive Biology Sciences Center for Alzheimer's and Neurodegenerative Diseases Center for the Genetics of Host Defense Center for Human Nutrition Center for Patient-Centered Outcomes Research Center for Translational Medicine Center for Translational Neurodegeneration Research Charles and Jane Pak Center for Mineral Metabolism and Clinical Research.

Children's Medical Center Research Institute at UT Southwestern Eugene McDermott Center for Human Growth and Development Hamon Center for Regenerative Science and Medicine Hamon Center for Therapeutic Oncology Research Harold C. Brain Institute Texas Institute for Brain Injury and Repair Touchstone Center for Diabetes Research.

Programs Disease-Oriented Clinical Scholars DOCS Endowed Scholars Program Kidney Cancer Program Medical Scientist Training Program MSTP Medical Student Research Programs Physician Scientist Training Program Science Teacher Access to Resources at Southwestern STARS Summer Undergraduate Research Fellowship Program SURF.

Apply to Medical School. Apply to Graduate School. Apply to School of Health Professions. Apply to School of Public Health. Terrien, J. Gender markedly modulates behavioral thermoregulation in a non-human primate species, the mouse lemur Microcebus murinus.

Noiret, A. Sex-specific response to caloric restriction after reproductive investment in Microcebus murinus: an integrative approach.

Aging and season affect plasma dehydroepiandrosterone sulfate DHEA-S levels in a primate. Thermoregulatory responses to variations of photoperiod and ambient temperature in the male lesser mouse lemur: a primitive or an advanced adaptive character? Energetic advantage of nest-sharing in a solitary primate, the lesser mouse lemur M icrocebus murinus.

Daily hypothermia and torpor in a tropical primate: synchronization by h light-dark cycle. Le Tallec, T. Light pollution modifies the expression of daily rhythms and behavior patterns in a nocturnal primate.

PLoS ONE 8 , e Article ADS PubMed PubMed Central CAS Google Scholar. IGF a marker of individual life-span in a primate. Breit, A. Insulin-like growth factor-1 acts as a zeitgeber on hypothalamic circadian clock gene expression via glycogen synthase kinase-3 signaling.

Crosby, P. Cell , e e20 Kendall, A. Effects of aging on the intrinsic circadian period of totally blind humans. Rhythms 16 , 87—95 Monk, T. The timing of bedtime and waketime decisions in free-running subjects.

Psychophysiology 26 , — Possidente, B. Aging lengthens circadian period for wheel-running activity in C57BL mice. Davis, F. Stability of circadian timing with age in Syrian hamsters.

Schilling, A. Effect of aging on circadian activity in gray mouse lemurs. Spoelstra, K. Natural selection against a circadian clock gene mutation in mice. Article ADS CAS PubMed Google Scholar.

Emerson, K. Concordance of the circadian clock with the environment is necessary to maximize fitness in natural populations. Evolution NY. Dal-pan, A. Age Omaha. Article CAS Google Scholar.

Landes, J. State transitions: a major mortality risk for seasonal species. Cox, D. Analysis of Survival Data. Monographs on Statistics and Applied Probability.

Kraus, C. The costs of risky male behaviour: Sex differences in seasonal survival in a small sexually monomorphic primate. B Biol. Download references. We are grateful to Aude Anzeray and Isabelle Hardy for their participation in the data collection.

You can also search for this author in PubMed Google Scholar. Conceptualization, C. and M. Investigation, C. Methodology and Formal Analysis, C. and F. Supervision, F. Correspondence to Fabien Pifferi.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.

The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Reprints and permissions. Survival is reduced when endogenous period deviates from 24 h in a non-human primate, supporting the circadian resonance theory.

Sci Rep 10 , Download citation. Received : 03 July Accepted : 08 October Published : 22 October Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. Skip to main content Thank you for visiting nature. nature scientific reports articles article. Download PDF. Subjects Evolution Physiology. Abstract Circadian rhythms are ubiquitous attributes across living organisms and allow the coordination of internal biological functions with optimal phases of the environment, suggesting a significant adaptive advantage.

Introduction The circadian clock is a pervasive feature, expressing biological rhythms that control a wide range of physiological, metabolic and behavioral traits 1 , 2 , 3 , 4 , 5 , 6.

Results Distribution of tau and correlation with age As found in many nocturnal species 8 , the gray mouse lemur clock oscillates with a period of less than 24 h Fig. Figure 1. Full size image. Figure 2. Endogenous periods according to age at measurement in the mouse lemurs tested.

Full size table. Figure 3. Discussion This study aimed at exploring the relationship between the endogenous period tau and survival in a non-human primate. Housing conditions All animals were housed in cages equipped with wood branches for climbing activities as well as wooden sleeping boxes mimicking the natural sleeping sites of mouse lemurs, i.

Telemetry implants Recording of locomotor activity LA was obtained by telemetry at a constant ambient temperature of 25 °C. Endogenous period measurement In order to measure the endogenous period tau , individuals included in the survey were isolated and submitted to free-running conditions i.

Mortality data In total, animals, with 91 males and 51 females were integrated in the study. Table 2 Mean age at death, age at tau measurement, number of natural deaths and censored individuals in male and female mouse lemurs.

References Barclay, J. Article PubMed Google Scholar Reinke, H. Article PubMed Google Scholar Kalsbeek, A. Article CAS PubMed PubMed Central Google Scholar Richards, J.

Article ADS CAS PubMed PubMed Central Google Scholar Aschoff, J. Article CAS PubMed Google Scholar Pittendrigh, C.

Article Google Scholar Duong, H. Article ADS CAS PubMed PubMed Central Google Scholar Pittendrigh, C. Article ADS CAS PubMed PubMed Central Google Scholar von Saint Paul, U.

Article CAS PubMed PubMed Central Google Scholar Libert, S. Article CAS PubMed Google Scholar Bons, N. Article CAS PubMed Google Scholar Joly, M. Article CAS PubMed Google Scholar Hozer, C. Article Google Scholar Aujard, F. Article CAS PubMed Google Scholar Pifferi, F.

Article CAS PubMed Google Scholar Perret, M. Article Google Scholar Lutermann, H. Article PubMed PubMed Central Google Scholar Génin, F.

Article CAS PubMed PubMed Central Google Scholar Pittendrigh, C. Article Google Scholar Nakamura, T. Article CAS PubMed PubMed Central Google Scholar Engelberth, R. Article Google Scholar Zhdanova, I. Google Scholar Jazwinski, S. Article CAS PubMed PubMed Central Google Scholar Cayetanot, F.

Article CAS PubMed Google Scholar Stanewsky, R. Article CAS PubMed Google Scholar Helfrich-Förster, C. Article Google Scholar Wever, R. Article CAS PubMed Google Scholar Duffy, J. Article ADS CAS PubMed PubMed Central Google Scholar Bailey, M. Article PubMed Google Scholar Goel, N.

Article CAS PubMed Google Scholar Schmid, J. Article Google Scholar Terrien, J. Article CAS PubMed Google Scholar Noiret, A. Article PubMed PubMed Central Google Scholar Perret, M. Article CAS PubMed Google Scholar Aujard, F. Article Google Scholar Perret, M. Article CAS PubMed Google Scholar Le Tallec, T.

Article ADS PubMed PubMed Central CAS Google Scholar Aujard, F. Article Google Scholar Breit, A. Article CAS PubMed PubMed Central Google Scholar Crosby, P.

Google Scholar Kendall, A. Article CAS PubMed Google Scholar Monk, T. Article CAS PubMed Google Scholar Possidente, B. Article CAS PubMed Google Scholar Davis, F. Google Scholar Schilling, A. Article Google Scholar Spoelstra, K. Article ADS CAS PubMed Google Scholar Emerson, K.

Article Google Scholar Dal-pan, A. Article CAS Google Scholar Landes, J. Article PubMed Google Scholar Cox, D. Article Google Scholar Download references.

Acknowledgements We are grateful to Aude Anzeray and Isabelle Hardy for their participation in the data collection.

View author publications. Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary information. The second process that greatly influences the onset, duration, and quality of your sleep is the phase of your circadian rhythm.

This phase is governed by your biological clock, whose rhythm is endogenous but is reset regularly by daylight. This clock therefore produces a cycle lasting about 24 hours during which the optimal times for falling asleep, dreaming, waking up, and doing work occur over the course of each day.

The external cues or zeitgebers German for "time-givers" - of which sunlight is the most important - entrain your endogenous internal body clock to fall in line with the earth's day. Endogenous sleep rhythms can be depicted graphically. The black lines indicate periods of sleep, and the gray lines indicate periods of wakefulness.

Thus your entire sleep-wake cycle operates as if your circadian oscillator made falling asleep easier at certain times of day, making you appreciably sleepier from PM to PM, and even sleepier from AM to AM.

These patterns are confirmed by the statistics on workplace and highway accidents. This two-process model - homeostatic and circadian - for regulating sleep can be diagrammed as a double pendulum. But when this relationship is disturbed and the two pendulums are no longer in phase, then the quality both of your sleep and of your performance when awake deteriorate significantly.

The peaks of activity for several circadian markers occur at inconvenient times in the sleep-wake cycle, which is the source of the problems caused by jet lag and by working night shifts. In other words, the longer you stay awake, the greater the pressure you will feel to go to sleep.

This process of homeostatic debt, or sleep debt, also explains why, if you stay up all night, then the next night, not only will you sleep longer, but your percentage of deep sleep will be higher. As each day draws to a close, you feel the need to lie down and go to sleep.

The onset of sleep, which seems like such a simple phenomenon from a behavioral perspective, is actually quite complex from a molecular one. It was in the early s that scientists first discovered the chemical mechanism by which drinking coffee helps people to stay awake: caffeine, the psychoactive substance in coffee, prevents adenosine from binding to certain neurons in the brain.

Both the caffeine in coffee and the theophylline in tea are examples of such adenosine antagonists and are well known for their stimulant effects. Once this discovery was made, adenosine became a subject of interest for more and more neurobiologists who were doing sleep research.

Some of the experimental findings that led to this conclusion: a blocking the effects of adenosine made animals more alert; b injecting animals with an adenosine agonist enhancer caused them to fall asleep; c in certain parts of the brain, the concentration of adenosine normally increases naturally during the day and decreases at night, but if animals are forced to stay awake at night, this concentration keeps increasing.

These experiments thus showed that adenosine, along with other chemicals such as serotonin and melatonin, is one of the molecules whose concentration in the brain influences the onset of sleep. The amount of adenosine produced in the brain thus reflects the activity level of its neurons and glial cells.

The accumulation of adenosine during waking periods is thus associated with the depletion of the ATP reserves stored as glycogen in the brain. The increased adenosine levels trigger non-REM sleep, during which the brain is less active, thus placing it in a recovery phase that is absolutely essential—among other things, to let it rebuild its stores of glycogen.

But how exactly does adenosine exert this influence? During periods of wakefulness, neuronal activity increases the concentration of adenosine, which has an inhibitory effect on a great many neurons.

Among these are the neurons of the hormonal systems that are the most active when we are awake: the norepinephrine, acetylcholine, and serotonin systems.

Experiments have shown, for example, that when the levels of adenosine in the basal forebrain are raised artificially, the neurons in this structure that project axons throughout the cortex produce less acetylcholine. As a result, cortical activity slows, and the individual falls asleep.

The synchronized brain activity characteristic of non-REM sleep can then become established. But once non-REM sleep has continued for a while, the adenosine levels begin to decline. The systems responsible for wakefulness can then start becoming more active, causing the individual to awaken and the cycle to begin all over again.

There are two important structures for the circadian cycle that could be considered our biological clocks. Instead, they fluctuate in hour cycles, such as the sleeping and waking cycle and the cycles for body temperature, hunger, and the secretion of various hormones.

The central clock that regulates all of these circadian cycles is located in two tiny structures in the brain, at the base of the left and right hypothalamus. Each of these structures is no larger than a pencil tip and contains several tens of thousands of neurons.

This strategic position enables the suprachiasmatic nuclei to receive projections from the optic nerve from special retinal ganglion cells that tell them about the intensity of the ambient light entering the eyes.

The neurons of these nuclei use this information to resynchronize themselves with daylight every day, because like any clock, the human biological clock is not perfect and does need to be reset periodically.

One interesting thing about the retinohypothalamic path is that it is separate from those for vision such that even blind people and blind mole rats, a species that is otherwise blind receive information from light to reset their biological clocks. Despite this need to resynchronize with an external cue, it has been shown that the suprachiasmatic nuclei do in fact constitute a biological clock with its own independent rhythm.

First, many experiments have shown that the fluctuations of the human circadian cycle persist even when individuals are cut off from the light of day.

And when suprachiasmatic nuclei were then transplanted from hamster fetuses into these animals, their biological rhythms returned, but with the properties of the donors. These findings indicate that the mammalian biological clock mechanism is in fact not only endogenous, but also of genetic origin.

Scientists have now even determined that these rhythms are the result of the cyclical activity of certain genes.

Melanopsin in retinal ganglion cells in the eye respond to light natural or artificially and transmit signals to the SCN.