Gene expression profiling of the SCN in young and old rhesus macaques

In mammals, the suprachiasmatic nucleus (SCN) is the location of a master circadian pacemaker. It receives photic signals from the environment via the retinal hypothalamic tract, which play a key role in synchronizing the body’s endogenously generated circadian rhythms with the 24-h rhythm of the environment. Therefore, it is plausible that age-related changes within the SCN contribute to the etiology of perturbed activity–rest cycles that become prevalent in humans during aging. To test this hypothesis, we used gene arrays and quantitative RT-PCR to profile age-related gene expression changes within the SCN of male rhesus macaques – a pragmatic translational animal model of human aging, which similarly displays an age-related attenuation of daytime activity levels. As expected, the SCN showed high expression of arginine vasopressin, vasoactive intestinal polypeptide, calbindin and nuclear receptor subfamily 1, group D, member 1 (NR1D1) (also known as reverse strand of ERBA (REV-ERBα), both at the mRNA and protein level. However, no obvious difference was detected between the SCNs of young (7–12 years) and old animals (21–26 years), in terms of the expression of core clock genes or genes associated with SCN signaling and neurotransmission. These data demonstrate the resilience of the primate SCN to normal aging, at least at the transcriptional level and, at least in males, suggest that age-related disruption of activity–rest cycles in humans may instead stem from changes within other components of the circadian system, such as desynchronization of subordinate oscillators in other parts of the body.

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Suprachiasmatic Nucleus Anatomy, Physiology, and Neurochemistry

Oxford Research Encyclopedia of Neuroscience ◽

10.1093/acrefore/9780190264086.013.27 ◽

2018 ◽

Cited By ~ 2

Author(s):

Rae Silver

Keyword(s):

Gene Expression ◽

Circadian Rhythms ◽

Electrical Activity ◽

Suprachiasmatic Nucleus ◽

Clock Gene ◽

Clock Genes ◽

Transgenic Animals ◽

The Body ◽

Network Activity ◽

Over Time

We live in an approximately 24-hour world and circadian rhythms have evolved to adapt organisms to the opportunities presented by Earth’s 24-hour cycle of light and dark. A “master clock” located in the suprachiasmatic nucleus (SCN) of the brain orchestrates daily rhythms in all manner of behavioral, endocrine, metabolic, autonomic, and homeostatic systems in our bodies. The SCN is comprised of about 20,000 neurons and about one third as many astroglia. How can so few neurons and astroglia guide so many rhythms? How do neurons time out an interval as long as a day? The answers are a case study in understanding how genes within cells, and cells within circuits, function together to perform complex activities and optimize bodily functions. While individual clock cells are found in virtually all bodily tissues, the unique connectome of the SCN, its specialized afferent inputs from the retinohypothalamic tract, and its neural and humoral outputs enable its “babel” of neuronal types to synchronize their activity and signal time to the rest of the body. At the molecular-cellular level, circadian rhythms are regulated by a 24-hour transcriptional–translational feedback loop. At the SCN tissue level, individual SCN neurons coordinate their gene expression and electrical activity, working together in circuits that sustain coherent rhythms. The SCN has many distinct cell types based on their neurotransmitters, neuropeptides, and afferent and efferent connections. There has been much progress in unraveling the dynamic network organization that underlies the SCN network’s communications. Though the precise anatomical connections underlying interneuronal communication in the SCN are not completely understood, key signaling mechanisms that sustain the SCN’s intrinsic rhythmicity have been tackled using intersectional genomic tools. Transgenic animals that permit the visualization of clock gene–protein expression have enabled analysis of SCN network activity over time. Availability of animals bearing mutations in clock genes or proteins enable the determination of changes within neurons, among neurons in networks, and their impact on behavior. The use of continuous readouts of circadian activity that track behavior, or clock gene expression, or electrical activity changes over time, within an SCN or a single neuron, leads the way to unraveling mechanisms sustaining the circadian timing system. Because the results of circadian studies generate huge amounts of data, the entry of mathematical modelers and statisticians into the field has begun to yield useful and testable predictions on how these multiplexed systems work to adapt to our 24-hour world.

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Lifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart

Physiological Genomics ◽

10.1152/physiolgenomics.00082.2002 ◽

2003 ◽

Vol 12 (2) ◽

pp. 129-138 ◽

Cited By ~ 61

Author(s):

A. M. Bronikowski ◽

P. A. Carter ◽

T. J. Morgan ◽

T. Garland ◽

N. Ung ◽

...

Keyword(s):

Gene Expression ◽

Selective Breeding ◽

Voluntary Exercise ◽

Transcriptional Level ◽

Expression Change ◽

Oligonucleotide Arrays ◽

Treatment Groups ◽

Active Population ◽

Sedentary Population ◽

Age Related

We present the first quantitative gene expression analysis of cardiac aging under conditions of sedentary and active lifestyles using high-density oligonucleotide arrays representing 11,904 cDNAs and expressed sequence tags (ESTs). With these data, we test the hypothesis that exercise attenuates the gene expression changes that normally occur in the aging heart. Male mice ( Mus domesticus) were sampled from the 16th generation of selective breeding for high voluntary exercise. For the selective breeding protocol, breeders were chosen based on the maximum number of wheel revolutions run on days 5 and 6 of a test at 8 wk of age. For the colony sampled herein, mice were housed individually over their entire lifetimes (from weaning) either with or without access to running wheels. The hearts of these two treatment groups (active and sedentary) were assayed at middle age (20 mo) and old age (33 mo). Genes significantly affected by age in the hearts of the sedentary population by at least a 50% expression change ( n = 137) were distributed across several major categories, including inflammatory response, stress response, signal transduction, and energy metabolism. Genes significantly affected by age in the active population were fewer ( n = 62). Of the 42 changes in gene expression that were common to both treatment groups, 32 (72%) displayed smaller fold changes as a result of exercise. Thus exercise offset many age-related gene expression changes observed in the hearts of the sedentary animals. These results suggest that adaptive physiological mechanisms that are induced by exercise can retard many effects of aging on heart muscle at the transcriptional level.

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Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart

Physiological Genomics ◽

10.1152/physiolgenomics.00172.2002 ◽

2003 ◽

Vol 13 (2) ◽

pp. 119-127 ◽

Cited By ~ 55

Author(s):

Michael G. Edwards ◽

Deepayan Sarkar ◽

Roger Klopp ◽

Jason D. Morrow ◽

Richard Weindruch ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Age Groups ◽

Transcriptional Level ◽

Mouse Heart ◽

Mrna Levels ◽

Middle Aged ◽

Transcriptional Responses ◽

Age Related ◽

Young Mice

To investigate the transcriptional response to oxidative stress in the heart and how it changes with age, we examined the cardiac gene expression profiles of young (5-mo-old), middle-aged (15-mo-old), and old (25-mo-old) C57BL/6 mice treated with a single intraperitoneal injection of paraquat (50 mg/kg). Mice were killed at 0, 1, 3, 5, and 7 h after paraquat treatment, and the gene expression profile was obtained with high-density oligonucleotide microarrays. Of 9,977 genes represented on the microarray, 249 transcripts in the young mice, 298 transcripts in the middle-aged mice, and 256 transcripts in the old mice displayed a significant change in mRNA levels (ANOVA, P < 0.01). Among these, a total of 55 transcripts were determined to be paraquat responsive for all age groups. Genes commonly induced in all age groups include those associated with stress, inflammatory, immune, and growth factor responses. Interestingly, only young mice displayed a significant increase in expression of all three isoforms of GADD45, a DNA damage-responsive gene. Additionally, the number of immediate early response genes (IEGs) found to be induced by paraquat was considerably higher in the younger animals. These results demonstrate that, at the transcriptional level, there is an age-related impairment of specific inducible pathways in the response to oxidative stress in the mouse heart.

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Global Age-Specific Patterns of Cyclic Gene Expression Revealed by Tunicate Transcriptome Atlas

10.1101/2020.12.08.417055 ◽

2020 ◽

Author(s):

Yotam Voskoboynik ◽

Aidan Glina ◽

Mark Kowarsky ◽

Chiara Anselmi ◽

Norma F Neff ◽

...

Keyword(s):

Gene Expression ◽

Clock Genes ◽

Tissue Level ◽

Cellular Aging ◽

Circadian Gene ◽

Age Related ◽

Global Age ◽

Cyclic Gene ◽

Circadian Clock Genes ◽

Aging Phenomena

AbstractExpression levels of circadian clock genes, which regulate 24-hour rhythms of behavior and physiology, have been shown to change with age. However, a study holistically linking aging and circadian gene expression is missing. Using the colonial chordate Botryllus schlosseri, we combined transcriptome sequencing and stem cell-mediated aging phenomena to test how circadian gene expression changes with age. This revealed that B. schlosseri clock and clock-controlled genes oscillate organism-wide, with daily, age-specific amplitudes and frequencies. These age-related, circadian patterns persist at the tissue level, where dramatic variations in cyclic gene expression of tissue profiles link to morphological and cellular aging phenotypes. Similar cyclical expression differences were found in hundreds of pathways associated with known hallmarks of aging, as well as pathways that were not previously linked to aging. The atlas we developed points to alterations in circadian gene expression as a key regulator of aging.One Sentence SummaryThe Ticking Clock: Systemic changes in circadian gene expression correlates with wide-ranging phenotypes of aging

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Daily temperature cycles prolong lifespan and have sex-specific effects on peripheral clock gene expression in Drosophila melanogaster

Journal of Experimental Biology ◽

10.1242/jeb.233213 ◽

2021 ◽

pp. jeb.233213

Author(s):

Grace H. Goh ◽

Dominique Blache ◽

Peter J. Mark ◽

W. Jason Kennington ◽

Shane K. Maloney

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Clock Gene ◽

Clock Genes ◽

Daily Temperature ◽

Peripheral Tissues ◽

Temperature Cycles ◽

Clock Gene Expression ◽

Age Related ◽

Temperature Rhythms

Circadian rhythms optimize health by coordinating the timing of physiological processes to match predictable daily environmental challenges. The circadian rhythm of body temperature is thought to be an important modulator of molecular clocks in peripheral tissues, but how daily temperature cycles impact physiological function is unclear. Here, we examined the effect of constant (25°C, TCON) and cycling (28°C/22°C during light/dark, TCYC) temperature paradigms on lifespan of Drosophila melanogaster, and the expression of clock genes, Heat shock protein 83 (Hsp83), Frost (Fst), and Senescence-associated protein 30 (smp-30). Male and female Drosophila housed at TCYC had longer median lifespans than those housed at TCON. TCYC induced robust Hsp83 rhythms and rescued the age-related decrease in smp-30 expression that was observed in flies at TCON, potentially indicating an increased capacity to cope with age-related cellular stress. Ageing under TCON led to a decrease in the amplitude of expression of all clock genes in the bodies of male flies, except for cyc, which was non-rhythmic, and for per and cry in female flies. Strikingly, housing under TCYC conditions rescued the age-related decrease in amplitude of all clock genes, and generated rhythmicity in cyc expression, in the male flies, but not the female flies. The results suggest that ambient temperature rhythms modulate Drosophila lifespan, and that the amplitude of clock gene expression in peripheral body clocks may be a potential link between temperature rhythms and longevity in male Drosophila. Longevity due to TCYC appeared predominantly independent of clock gene amplitude in female Drosophila.

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Immature Pear Extract Constituents Exert Multifaceted Anti-aging Effects

Innovation in Aging ◽

10.1093/geroni/igab046.2551 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 684-684

Author(s):

Akira Ogita ◽

Wakae Murata ◽

Ken Yamauchi ◽

Akiko Sakai ◽

Yoshihiro Yamaguchi ◽

...

Keyword(s):

Gene Expression ◽

Cellular Senescence ◽

Mammalian Cells ◽

Human Life ◽

The Body ◽

Yeast Cells ◽

Related Gene ◽

Aging Effects ◽

Chronological Lifespan ◽

Age Related

Abstract Cellular senescence causes a gradual loss of physiological functions and induces chronic diseases, which negatively affect the quality of human life. Intervention in the cellular senescence process may reduce the incidence of these diseases while delaying the progression of age-related diseases, thereby prolonging human lifespan. In our previous study, we found that extending the chronological lifespan of budding yeast cells, a suitable cellular model for research on mammalian cells, could be achieved by adding immature pear extract (iPE). Moreover, at the 2020 GSA meeting, using a colony-counting method, we reported that both hydrophilic (WiPE) and hydrophobic (OiPE) iPE components exhibited a chronological lifespan prolongation on yeast cells. In this study, the expression of sirtuin-related genes, which regulate cellular senescence, was verified by quantitative real-time reverse-transcription polymerase chain reaction. Interestingly, sirtuin-related gene expression was significantly increased in the WiPE-treated cells only, and OiPE could extend the chronological lifespan of yeast cells through the mechanisms not involved in sirtuin-related gene expression. In general, hydrophobic and hydrophilic components exhibit different degradation and metabolism in cells. Since each component has a different strategy of absorption and excretion in the body, we hypothesize that iPE with multiple active components will have multifaceted effects on anti-aging. Our research on elucidating the mechanism of lifespan extension by OiPE and its application to mammalian cells is ongoing.

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Gene expression in hypothalamus and brown adipose tissue of mice divergently selected for heat loss

Physiological Genomics ◽

10.1152/physiolgenomics.2000.3.3.149 ◽

2000 ◽

Vol 3 (3) ◽

pp. 149-156 ◽

Cited By ~ 13

Author(s):

MARK F. ALLAN ◽

MERLYN K. NIELSEN ◽

DANIEL POMP

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Heat Loss ◽

Expressed Sequence Tag ◽

Northern Analysis ◽

Transcriptional Level ◽

Activity Levels ◽

Direct Calorimetry ◽

Brown Adipose

Allan, Mark F., Merlyn K. Nielsen, and Daniel Pomp. Gene expression in hypothalamus and brown adipose tissue of mice divergently selected for heat loss. Physiol Genomics 3: 149–156, 2000.—Gene expression was evaluated in mice divergently selected for 16 generations for heat loss, measured by direct calorimetry. The high (MH) heat loss line has ∼50% greater heat loss, ∼35% less body fat, ∼20% greater feed intake, and twofold greater activity levels than the low (ML) heat loss line. At 11 wk, inbred males (developed from MH and ML) were euthanized 3 h after dark for dissection of tissues and extraction of RNA. Differential display PCR (DD-PCR) was used to evaluate transcriptional differences between lines in hypothalamus and brown adipose tissue (BAT). Evaluation was replicated within and across lines, using family pools of mRNA. Two genes were confirmed by competitive RT-PCR and/or Northern analysis to have greater levels of mRNA present in ML relative to MH mice. In both hypothalamus and BAT, the ribosomal protein L3 ( RPL3) gene was expressed at higher levels in ML, whereas an unknown expressed sequence tag (EST) was also found at higher levels in the hypothalamus of ML mice. These results implicate RPL3 in regulation of energy balance and extend the genetic dissection of response to selection to the transcriptional level.

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Brain histone beta-hydroxy-butyrylation couples metabolism with gene expression

10.1101/2021.06.28.449924 ◽

2021 ◽

Author(s):

Sara Cornuti ◽

Leonardo Lupori ◽

Siwei Chen ◽

Francesco Finamore ◽

Muntaha Samad ◽

...

Keyword(s):

Gene Expression ◽

Cerebral Cortex ◽

Clock Genes ◽

Neurological Diseases ◽

Transcriptional Level ◽

Functional Annotations ◽

Ketogenic Diets ◽

Brain Resilience ◽

Beta Hydroxybutyrate ◽

The Impact

The metabolic status has a well-documented influence on peripheral organs' physiology and pathology, however mounting evidence suggests that it can also affect brain function. For example, brain resilience to aging is enhanced by caloric restriction, and ketogenic diets have been used to treat neurological diseases. Unfortunately, little is known about the impact of metabolic stimuli on brain tissue at a molecular level. Recent data obtained in liver tissue suggest that beta-hydroxybutyrate (BHB) can also be a key signaling molecule regulating gene transcription. Thus, we adopted a ketogenic metabolic challenge, based on 48 hrs of fasting, and then assessed lysine beta-hydroxybutyrylation (K-bhb) levels in proteins extracted from the cerebral cortex. We found that fasting enhanced K-bhb in a variety of proteins and on histone H3. ChIP-seq experiments showed that K9 beta-hydroxybutyrylation of H3 (H3K9-bhb) was significantly enriched by fasting on more than 8000 DNA loci. Transcriptomic analysis showed that H3K9-bhb on enhancers and promoters correlated with active gene expression. Since one of the most enriched functional annotations both at the epigenetic and transcriptional level was circadian rhythms, we studied the expression of core-clock genes in the cortex during fasting. We found that the diurnal oscillation of specific transcripts was modulated at distinct times of the day along the circadian cycle. Thus, our results suggest that fasting dramatically impinges on the cerebral cortex transcriptional and epigenetic landscape, and BHB acts as a powerful epigenetic molecule in the brain through direct and specific histone marks remodelling in neural tissue cells.

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Chronobiology and Metabolism: Is Ketogenic Diet Able to Influence Circadian Rhythm?

Frontiers in Neuroscience ◽

10.3389/fnins.2021.756970 ◽

2021 ◽

Vol 15 ◽

Author(s):

Elena Gangitano ◽

Lucio Gnessi ◽

Andrea Lenzi ◽

David Ray

Keyword(s):

Gene Expression ◽

Circadian Rhythm ◽

Circadian Clock ◽

Ketogenic Diet ◽

Clock Genes ◽

The Body ◽

Acid Oxidation ◽

Metabolic Switch ◽

Peripheral Tissues ◽

Central Clock

Circadian rhythms underpin most physiological processes, including energy metabolism. The core circadian clock consists of a transcription-translation negative feedback loop, and is synchronized to light-dark cycles by virtue of light input from the retina, to the central clock in the suprachiasmatic nucleus in the hypothalamus. All cells in the body have circadian oscillators which are entrained to the central clock by neural and humoral signals. In addition to light entrainment of the central clock in the brain, it now emerges that other stimuli can drive circadian clock function in peripheral tissues, the major one being food. This can then drive the liver clock to be misaligned with the central brain clock, a situation of internal misalignment with metabolic disease consequences. Such misalignment is prevalent, with shift workers making up 20% of the working population. The effects of diet composition on the clock are not completely clarified yet. High-fat diet and fasting influence circadian expression of clock genes, inducing phase-advance and phase-delay in animal models. Ketogenic diet (KD) is able to induce a metabolic switch from carbohydrate to fatty acid oxidation, miming a fasting state. In recent years, some animal studies have been conducted to investigate the ability of the KD to modify circadian gene expression, and demonstrated that the KD alters circadian rhythm and induces a rearrangement of metabolic gene expression. These findings may lead to new approaches to obesity and metabolic pathologies treatment.

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The influence of osteopathic correction on the rate of various rhythms of the body

Russian Osteopathic Journal ◽

10.32885/2220-0975-2019-1-2-64-71 ◽

2019 ◽

pp. 64-71 ◽

Cited By ~ 1

Author(s):

A. E. Chernikova ◽

Yu. P. Potekhina

Keyword(s):

Heart Rate ◽

Respiratory Rate ◽

Age Groups ◽

Biomechanical Properties ◽

Dispersion Analysis ◽

The Body ◽

Body Tissues ◽

Age Related ◽

Significant Difference ◽

Before And After

Introduction. An osteopathic examination determines the rate, the amplitude and the strength of the main rhythms (cardiac, respiratory and cranial). However, there are relatively few studies in the available literature dedicated to the influence of osteopathic correction (OC) on the characteristics of these rhythms.Goal of research — to study the influence of OC on the rate characteristics of various rhythms of the human body.Materials and methods. 88 adult osteopathic patients aged from 18 to 81 years were examined, among them 30 men and 58 women. All patients received general osteopathic examination. The rate of the cranial rhythm (RCR), respiratory rate (RR) heart rate (HR), the mobility of the nervous processes (MNP) and the connective tissue mobility (CTM) were assessed before and after the OC session.Results. Since age varied greatly in the examined group, a correlation analysis of age-related changes of the assessed rhythms was carried out. Only the CTM correlated with age (r=–0,28; p<0,05) in a statistically significant way. The rank dispersion analysis of Kruskal–Wallis also showed statistically significant difference in this indicator in different age groups (p=0,043). With the increase of years, the CTM decreases gradually. After the OC, the CTM, increased in a statistically significant way (p<0,0001). The RCR varied from 5 to 12 cycles/min in the examined group, which corresponded to the norm. After the OC, the RCR has increased in a statistically significant way (p<0,0001), the MNP has also increased (p<0,0001). The initial heart rate in the subjects varied from 56 to 94 beats/min, and in 15 % it exceeded the norm. After the OC the heart rate corresponded to the norm in all patients. The heart rate and the respiratory rate significantly decreased after the OC (р<0,0001).Conclusion. The described biorhythm changes after the OC session may be indicative of the improvement of the nervous regulation, of the normalization of the autonomic balance, of the improvement of the biomechanical properties of body tissues and of the increase of their mobility. The assessed parameters can be measured quickly without any additional equipment and can be used in order to study the results of the OC.

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