The molecular athlete: exercise physiology from mechanisms to medals

Physiological Reviews, Год журнала: 2023, Номер 103(3), С. 1693 - 1787

Опубликована: Янв. 5, 2023

Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels endurance strength elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding signal integration, interpretation, output coordination cellular molecular mechanisms that govern plasticity across this continuum is incomplete. As such, training methods their application largely rely on “trial-and-error” approach, experience practices successful coaches often providing bases for “post hoc” scientific enquiry research. This review provides synopsis morphological functional changes along underlying adaptation endurance- resistance-based training. These traits are placed in context innate genetic interindividual differences performance, special consideration given aging athletes. Collectively, we provide comprehensive overview response different modes how such adaptations translate “molecules medals.”

Язык: Английский

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Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report

Hypertension, Год журнала: 2022, Номер 80(3), С. 503 - 522

Опубликована: Ноя. 30, 2022

Healthy individuals exhibit blood pressure variation over a 24-hour period with higher during wakefulness and lower sleep. Loss or disruption of the circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, chronic kidney disease. However, current diagnostic therapeutic approaches lack sufficient attention rhythmicity pressure. Sleep patterns, hormone release, eating habits, digestion, body temperature, renal function, other important host functions as well gut microbiota rhythms, influence rhythms Potential benefits nonpharmacologic interventions such meal timing, pharmacologic chronotherapeutic interventions, bedtime administration antihypertensive medications, have recently suggested in some studies. mechanisms underlying rhythm-mediated regulation efficacy chronotherapy hypertension remain unclear. This review summarizes results National Heart, Lung, Blood Institute workshop convened on October 27 29, 2021 assess knowledge gaps research opportunities study hypertension.

Язык: Английский

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Circadian clocks of the kidney: function, mechanism, and regulation

Physiological Reviews, Год журнала: 2022, Номер 102(4), С. 1669 - 1701

Опубликована: Май 16, 2022

An intrinsic cellular circadian clock is located in nearly every cell of the body. The peripheral clocks within cells kidney contribute to regulation a variety renal processes. In this review, we summarize what currently known regarding function, mechanism, and clocks. Additionally, effect extrarenal physiological processes, such as endocrine neuronal signals, on function also reviewed. Circadian rhythms are an integral part physiology, underscoring importance considering time day key biological variable. field physiology tremendous relevance, but with limited mechanistic information area need extensive investigation.

Язык: Английский

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Diurnal timing of physical activity in relation to obesity and diabetes in the German National Cohort (NAKO)

International Journal of Obesity, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Язык: Английский

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Wearables in Chronomedicine and Interpretation of Circadian Health

Diagnostics, Год журнала: 2025, Номер 15(3), С. 327 - 327

Опубликована: Янв. 30, 2025

Wearable devices have gained increasing attention for use in multifunctional applications related to health monitoring, particularly research of the circadian rhythms cognitive functions and metabolic processes. In this comprehensive review, we encompass how wearables can be used study disease. We highlight importance these as markers well-being potential predictors outcomes. focus on wearable technologies sleep research, medicine, chronomedicine beyond domain emphasize actigraphy a validated tool monitoring sleep, activity, light exposure. discuss various mathematical methods currently analyze actigraphic data, such parametric non-parametric approaches, linear, non-linear, neural network-based applied quantify non-circadian variability. also introduce novel actigraphy-derived markers, which personalized proxies status, assisting discriminating between disease, offering insights into neurobehavioral status. lifestyle factors physical activity exposure modulate brain health. establishing reference standards measures further refine data interpretation improve clinical The review calls existing tools methods, deepen our understanding health, develop healthcare strategies.

Язык: Английский

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Analysis of mammalian circadian clock protein complexes over a circadian cycle

Journal of Biological Chemistry, Год журнала: 2023, Номер 299(3), С. 102929 - 102929

Опубликована: Янв. 20, 2023

Circadian rhythmicity is maintained by a set of core clock proteins including the transcriptional activators CLOCK and BMAL1, repressors PER (PER1, PER2, PER3), CRY (CRY1 CRY2), CK1δ. In mice, peak expression in early morning reduces CLOCK- BMAL1-mediated transcription/translation themselves. By late afternoon are largely depleted degradation, thereby their reactivated cycle repeated every 24 h. Studies have characterized variety possible protein interactions complexes associated with function this transcription–translation feedback loop. Our prior investigation suggested there were two circadian responsible for rhythmicity, one containing CLOCK–BMAL other CRY1, investigation, we acquired data from glycerol gradient centrifugation gel filtration chromatography mouse liver extracts obtained at different times to further characterize complexes. addition, anti-PER2 anti-CRY1 immunoprecipitates same analyzed liquid chromatography–tandem mass spectrometry identify components results confirm presence discrete CLOCK–BMAL1 PER–CRY–CK1δ time points, provide masses 255 707 kDa, respectively, these complexes, indicate that composed principally proteins. The mammalian controls many aspects physiology behavior, allowing organisms live sync daily light/dark cycle. manifestations follow cyclical circadian-controlled genes (CCGs) cells throughout body (1Reppert S.M. Weaver D.R. Coordination timing mammals.Nature. 2002; 418: 935-941Crossref PubMed Scopus (3505) Google Scholar, 2Hastings M.H. Reddy A.B. Maywood E.S. A clockwork web: brain periphery, health disease.Nat. Rev. Neurosci. 2003; 4: 649-661Crossref (976) 3Partch C.L. Green C.B. Takahashi J.S. Molecular architecture clock.Trends Cell Biol. 2014; 24: 90-99Abstract Full Text PDF (945) 4Patke A. Young M.W. Axelrod S. mechanisms physiological importance rhythms.Nat. Mol. 2020; 21: 67-84Crossref (496) 5Healy K.L. Morris A.R. Liu A.C. synchrony: sleep, nutrition, physical activity.Front. Netw. Physiol. 2021; 1: 732243Crossref (12) Scholar). Expression CCGs controlled via E-box elements promoters, which activator complex binds. Repressors include PER3, themselves CCGs, body, rhythm beginning CCG activation CLOCK–BMAL1, PERs, CRYs, latter then translocated nucleus where they repress CLOCK–BMAL1-mediated expression. Following degradation repressors, gene begins again (6Ye R. Selby C.P. Chiou Y.Y. Ozkan-Dagliyan I. Gaddameedhi Sancar Dual modes CLOCK:BMAL1 inhibition mediated Cryptochrome Period clock.Genes Dev. 28: 1989-1998Crossref (157) 7Sancar Mechanisms DNA repair photolyase excision nuclease (nobel lecture).Angew. Chem. Int. Ed. Engl. 2016; 55: 8502-8527Crossref (174) 8Sancar Van Gelder R.N. Clocks, cancer, chronochemotherapy.Science. 371eabb0738Crossref (116) 9Shearman L.P. Sriram Chaves Zheng B. et al.Interacting molecular loops clock.Science. 2000; 288: 1013-1019Crossref (1153) 10Levi F. Schibler U. rhythms: therapeutic implications.Annu. Pharmacol. Toxicol. 2007; 47: 593-628Crossref (500) 11Koch A.A. Bagnall Smyllie N.J. Begley N. Adamson A.D. Fribourgh J.L. al.Quantification abundance interaction defines mechanism operation clock.Elife. 2022; 11e73976Crossref (9) Besides main loop, clock-controlled REV–ERBα REV–ERBβ regulators BMAL1 secondary "loops" contribute stabilizing (10Levi Interestingly, chromation immunoprecipitation, immunoprecipitation (IP), expression–based studies indicated repression CLOCK–BMAL1-activated transcription occurs mechanisms: alone apparently binds directly represses ("blocking-type repression"), or PER–CK1δ, CRY-dependent manner, removes ("dissociation-type repression") 12Ye Ozturk Annayev Y. Biochemical analysis canonical model clock.J. 2011; 286: 25891-25902Abstract (105) 13Chiou Yang Rashid Ye Mammalian de-represses displacing CLOCK-BMAL1 promoters Cryptochrome-dependent manner.Proc. Natl. Acad. Sci. 113: e6072-e6079Crossref (97) 14Xu H. Gustafson Sammons P.J. Khan S.K. Parsley N.C. Ramanathan C. al.Cryptochrome 1 regulates through dynamic C terminus.Nat. Struct. 2015; 22: 476-484Crossref (110) 15Cao X. Z. repressive phase clock.Proc. 118e2021174118Crossref (56) 16An Yuan Xie P. Gu Wang T. al.Decoupling phosphorylation, stability rhythmic abolishing PER-CK1 interaction.Nat. Commun. 13: 3991Crossref (7) dissociation-type repression, aids bringing PER–CK1δ activator; CK1δ phosphorylates so as destabilize its association DNA. Biochemists long attempted activity For phase, found bind E-boxes heterodimer (17Hogenesch J.B. Y.Z. Jain Bradfield C.A. basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active hypoxia factors.Proc. 1998; 95: 5474-5479Crossref (641) 18Gekakis Staknis D. Nguyen H.B. Davis F.C. Wilsbacher L.D. King D.P. al.Role mechanism.Science. 280: 1564-1569Crossref (1602) 19Huang Chelliah Shan Taylor Yoo S.H. Partch al.Crystal structure heterodimeric complex.Science. 2012; 337: 189-194Crossref (228) investigations proteins, CLOCK, mPER2, mCRY2 reported form wide range sizes (200–5000 kDa) based upon (20Lee Etchegaray J.P. Cagampang F.R. Loudon A.S. Reppert Posttranslational regulate clock.Cell. 2001; 107: 855-867Abstract (951) Since then, additional using filtration, coimmunoprecipitation, blue native-agarose electrophoresis discovered PER-containing non–circadian RNAs, capable assembling megadalton-sized PERs (21Brown S.A. Ripperger J. Kadener Fleury-Olela Vilbois Rosbash M. al.PERIOD1-associated modulate negative limb oscillator.Science. 2005; 308: 693-696Crossref (223) 22Duong H.A. Robles M.S. Knutti Weitz C.J. feedback.Science. 332: 1436-1439Crossref (227) 23Etchegaray DeBruyne Peters Jenuwein al.The polycomb group EZH2 required function.J. 2006; 281: 21209-21215Abstract (141) 24Kim J.Y. Kwak P.B. Specificity targeted reconstitution NuRD corepressor.Mol. Cell. 56: 738-748Abstract (67) 25Padmanabhan K. Westerling Feedback regulation termination PERIOD 599-602Crossref (125) 26Aryal R.P. Tamayo A.G. Gebert Chiu P.L. Walz al.Macromolecular assemblies clock.Mol. 2017; 67: 770-782.e776Abstract (151) 27Kim Duong Purification clock.Methods Enzymol. 551: 197-210Crossref (14) However, several factors be present substoichiometric amounts (26Aryal Scholar), it unclear whether integral components, partners involved noncanonical nonclock functions (28Kriebs Jordan S.D. Soto E. Henriksson Sandate C.R. Vaughan M.E. al.Circadian CRY1 CRY2 broadly interact nuclear receptors activity.Proc. 114: 8776-8781Crossref (66) 29Partch Shields K.F. Thompson cryptochrome phosphatase 5.Proc. 103: 10467-10472Crossref (73) 30Chan Huber A.L. Lamia K.A. Cryptochromes E2F family factors.Sci. Rep. 10: 4077Crossref (15) 31Hara Onishi Oishi Miyazaki Fukamizu Ishida characterization Mybbp1a co-repressor on Period2 promoter.Nucl. Acids Res. 2009; 37: 1115-1126Crossref (33) 32Koike Huang H.C. Kumar V. Lee Kim T.K. al.Transcriptional chromatin landscape mammals.Science. 338: 349-354Crossref (1015) simply comingled concentrated mixtures. more recent sedimentation made liver, identified second, larger (15Cao As studies, standards included gradients estimate since separate coefficient (S), not mass, such estimates may accurate. To probe structure–function relationships used both obtain values S Stokes radius (R) These values, describe size shape globular nonglobular proteins/complexes, can combination described previously calculate proteins/complexes (33Siegel L.M. Monty K.J. Determination weights frictional ratios impure systems use density centrifugation. Application crude preparations sulfite hydroxylamine reductases.Biochim. Biophys. Acta. 1966; 112: 346-362Crossref (1653) 34Erickson H.P. Size molecules nanometer level determined sedimentation, electron microscopy.Biol. Proced. Online. 11: 32-51Crossref (1092) We also performed IPs PER2 antibodies followed (LC-MS/MS) identification (CLOCK–BMAL1) repressor (PER–CRY–CK1δ) assign respectively. show consist structural basis functioning. examine interactions, livers harvested six points (ZT0, ZT2, ZT6, ZT12, ZT16, ZT19) mixed markers subjected centrifugation, fractions specific Western blotting, outlined Figure 1A S1. served representative CRYs most reliably measured. study approach, ZT19, when levels, complexes: CLOCK–BMAL, migrated position corresponding approximately 200 CRY, PER, CK1δ, comigrated 550 kDa. Scholar) migration but coefficient. goal current directly, toward end will consider coefficients (S) radii discussed below. Sedimentation profiles shown Figures 1B elution PER–CRY–CK1δ, especially ZT19 levels highest, mobility 7.9S does change appreciably time, overlap, although trend BMAL lower value perhaps owing limiting formation, CLOCK-free migrating monomer smaller protein(s). relatively constant across consistent fact known vary considerably time. An apparent migrates 15.6S times, peaks. At extreme, undetected, all CK1 monomeric. When intermediate migrate S-value fractions. Thus, during much day, appears formation complement above effort precise weights, examined approach 2A. Nuclear prepared starting material. rather than mixing samples, column was standardized (Fig. S2). 2B gradients, sizing separated into separate, exhibits 7.7 nm, R = 10.79 nm. Trends seen results. one, CLOCK-containing fractions, indicating component formation. Regarding complex, factor increasing lower-R-value reduced. Notably, absence detectable an 5.4 Based results, calculated Methods Table 1. find weight about multimers PER1, CRY2, Ck1ε, (see below). It single homogeneous if multiple composition CRYs. heterodimer, somewhat size. This discrepancy partly due posttranslational modifications. observed indicates behavior influenced itself dimer, BMAL2, NPAS2, CRY1.Table 1Molecular complexesComplexCalculationMassComponentsPER–CRY–CK14205∗15.6∗10.794205∗7.9∗7.7707 kDaPER1-3, CRY1-2, CK1CLOCK–BMAL1CLOCK/BMAL1255 kDaPER1136 kDaPER2137 kDaPER3132 kDaCRY166 kDaCRY267 kDaCK1δ44 kDaCK1ε43 kDaCLOCK96 kDaBMAL169 kDaMolecular PERCRY–CK1 CLOCK–BMAL1complexes (as Methods) product 4205 x Components PER–CRY–CK1 shown; however, exists population each amounts/stoichiometries Below individual listed masses, sequence. experimentally derived value. modifications complex. three experiments gave fraction relation experiment. way assess potential variability assuming earlier later. case had been later, 707-kDa would 875 589 255-kDa 336 171 793 557 282 215 Open table new tab finding activate binding complex(s), immunoprecipitated either bound LC-MS/MS (Tables S1 ZT0, S3). Negative precipitating wildtype extract antibody IgM instead (IgM) antibody, Cry1/2−/− knockout mice wildtype. presented volcano plots 3, dots plotted represent detected, ratio amount test versus control (x-axis) significance (y-axis). (A) shows control, (B) Cry1/2−/−knockout control. Colored significant interactors experiment, ZT0. More double knockouts 11 mostly 3B), suggesting introduced artifactual interactions. dataset, comparing filtered lists controls, only eight overlapped, 3C). 3D interactive network generated STRING. coupled findings support existence known, implies identifies interactors. While could bona fide because did comigrate substantially (Figs. 2), seems likely separately limited manner function. immunopurification done sacrificed S4). Per1/2 mice. (Table S2) 107 IgG 86 4, B). Venn diagram 4C 13 consistently among repeats groups. (STRING) 4D CRY1. showing essentially noted above, clear BMAL, NPAS2 complex; confirms extends our comprising clarifies (PER–CRY–CK1δ complex) kDa (CLOCK–BMAL) stoichiometric excess (CRY, BMAL) eluted size, trailing profile these. peaks tended become prominent (and CRY) decreased nadir ZT6. Consistent observation 1:1 stoichiometry (35Schmalen Reischl Wallach Klemz Grudziecki Prabu J.R. al.Interaction modulated zinc bindi

Язык: Английский

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The time-evolving epileptic brain network: concepts, definitions, accomplishments, perspectives

Frontiers in Network Physiology, Год журнала: 2024, Номер 3

Опубликована: Янв. 16, 2024

Epilepsy is now considered a network disease that affects the brain across multiple levels of spatial and temporal scales. The paradigm shift from an epileptic focus—a discrete cortical area which seizures originate—to widespread network—spanning lobes hemispheres—considerably advanced our understanding epilepsy continues to influence both research clinical treatment this multi-faceted high-impact neurological disorder. network, however, not static but evolves in time requires novel approaches for in-depth characterization. In review, we discuss conceptual basics theory critically examine state-of-the-art recording techniques analysis tools used assess characterize time-evolving human network. We give account on current shortcomings highlight potential developments towards improved management epilepsy.

Язык: Английский

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Circadian Rhythms and Lung Cancer in the Context of Aging: A Review of Current Evidence

Aging and Disease, Год журнала: 2025, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2025

Circadian rhythm is the internal homeostatic physiological clock that regulates 24-hour sleep/wake cycle. This biological helps to adapt environmental changes such as light, dark, temperature, and behaviors. Aging, on other hand, a process of results in progressive decline cells, tissues, vital systems body. Both aging circadian are highly interlinked phenomena with bidirectional relationship. The leads disruptions while dysfunctional rhythms promote age-related complications. processes involve diverse physiological, molecular, cellular modifications DNA repair mechanisms, ROS generation, apoptosis, cell proliferation. review aims examine role context lung cancer. will also existing literature vice versa. Various molecular pathways genes BMAL1, SIRT1, HLF, PER1 their implications aging, rhythms, cancer be discussed.

Язык: Английский

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‘Help yourself, so the (circadian) rhythms help you’: Chronobiological insights to promote physical and mental health

Journal of Psychosomatic Research, Год журнала: 2025, Номер unknown, С. 112072 - 112072

Опубликована: Фев. 1, 2025

Язык: Английский

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Hair Follicles as a Critical Model for Monitoring the Circadian Clock

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2407 - 2407

Опубликована: Янв. 26, 2023

Clock (circadian) genes are heterogeneously expressed in hair follicles (HFs). The can be modulated by both the central circadian system and some extrinsic factors, such as light thyroid hormones. These participate regulation of several physiological processes HFs, including growth pigmentation. On other hand, because peripheral synchronized with clock, HFs could provide a noninvasive practical method for monitoring evaluating multiple circadian-rhythm-related conditions disorders among humans, day night shifts, sleep-wake disorders, physical activities, energy metabolism, aging. However, due to complexity biology, understanding how intrinsic oscillation operates using tissues only may insufficient. Combining HF sampling multidimensional assays detection body temperature, blood samples, or certain validated questionnaires helpful improving applications. Thus, serve critical model clock help an potential mechanisms conditions; furthermore, chronotherapy support personalized treatment scheduling based on gene expression profile HFs.

Язык: Английский

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