2021
Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10: e66522. PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/elife.66522.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietCoronavirus infectionAged miceT cellsHigher systemic inflammationInfected aged miceCOVID-19 severityCOVID-19 infectionActivation of ketogenesisMouse hepatitis virus strain A59Systemic inflammationInflammatory damageInfluenza infectionClinical hallmarkNLRP3 inflammasomeImmune surveillanceAdipose tissuePotential treatmentInfectionMiceStrongest predictorLungMortalityAge
2019
Mitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging
Seli E, Wang T, Horvath TL. Mitochondrial unfolded protein response: a stress response with implications for fertility and reproductive aging. Fertility And Sterility 2019, 111: 197-204. PMID: 30691623, DOI: 10.1016/j.fertnstert.2018.11.048.Peer-Reviewed Original ResearchConceptsMitochondrial unfolded protein responseTwo-cell embryo developmentUnfolded protein responseImpaired oocyte maturationMorphology of mitochondriaMitochondrial dysfunction resultsPremature reproductive agingNovel mechanistic insightsMitochondrial DNA contentReactive oxygen species productionPrevention of agingCLPP resultsProtein responseOxygen species productionReproductive agingPreimplantation embryosAge-related accumulationOxidative phosphorylationStress responseEmbryo developmentForm blastocystsMitochondrial functionMitochondriaMitochondrial dysfunctionEnergy metabolism
2015
Reducing Adiposity in a Critical Developmental Window Has Lasting Benefits in Mice
Lerea JS, Ring LE, Hassouna R, Chong AC, Szigeti-Buck K, Horvath TL, Zeltser LM. Reducing Adiposity in a Critical Developmental Window Has Lasting Benefits in Mice. Endocrinology 2015, 157: 666-678. PMID: 26587784, PMCID: PMC4733128, DOI: 10.1210/en.2015-1753.Peer-Reviewed Original ResearchConceptsDietary interventionBrown adipose tissue thermogenesisWeight lossEarly-onset hyperphagiaRapid weight regainEarly-onset obesityEnergy expenditureAdipose tissue thermogenesisCritical developmental windowWeight regainSympathetic toneMetabolic improvementHypothalamic leptinTissue thermogenesisEarly interventionCompensatory decreaseUnfavorable responseMiceMost adultsObesityAdiposityInterventionDevelopmental windowAdultsBrown adipose tissue mitochondria
2011
High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons
Klöckener T, Hess S, Belgardt BF, Paeger L, Verhagen LA, Husch A, Sohn JW, Hampel B, Dhillon H, Zigman JM, Lowell BB, Williams KW, Elmquist JK, Horvath TL, Kloppenburg P, Brüning JC. High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons. Nature Neuroscience 2011, 14: 911-918. PMID: 21642975, PMCID: PMC3371271, DOI: 10.1038/nn.2847.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAge FactorsAnimalsAnimals, NewbornBlood GlucoseBody WeightCalorimetryDietary FatsDose-Response Relationship, DrugEatingEnzyme InhibitorsEnzyme-Linked Immunosorbent AssayFemaleGene Expression RegulationGlucose Tolerance TestGreen Fluorescent ProteinsHypoglycemic AgentsIn Vitro TechniquesInjections, IntraventricularInsulinLeptinMaleMiceMice, Inbred C57BLMice, TransgenicNeuronsObesityPatch-Clamp TechniquesPhosphatidylinositol 3-KinasesReceptor, InsulinRNA, MessengerSignal TransductionSteroidogenic Factor 1Time FactorsTolbutamideVentromedial Hypothalamic Nucleus
2010
Early-Life Experience Reduces Excitation to Stress-Responsive Hypothalamic Neurons and Reprograms the Expression of Corticotropin-Releasing Hormone
Korosi A, Shanabrough M, McClelland S, Liu ZW, Borok E, Gao XB, Horvath TL, Baram TZ. Early-Life Experience Reduces Excitation to Stress-Responsive Hypothalamic Neurons and Reprograms the Expression of Corticotropin-Releasing Hormone. Journal Of Neuroscience 2010, 30: 703-713. PMID: 20071535, PMCID: PMC2822406, DOI: 10.1523/jneurosci.4214-09.2010.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnalysis of VarianceAnimalsAnimals, NewbornChromatin ImmunoprecipitationCorticotropin-Releasing HormoneExcitatory Amino Acid AntagonistsFemaleGene Expression Regulation, DevelopmentalMaleMaternal DeprivationMicroscopy, Electron, TransmissionNeuronsParaventricular Hypothalamic NucleusPatch-Clamp TechniquesPhysical StimulationPregnancyRatsRats, Sprague-DawleyRepressor ProteinsRNA, MessengerSodium Channel BlockersStress, PsychologicalSynaptic PotentialsTetrodotoxinVesicular Glutamate Transport Protein 2ConceptsCorticotropin-releasing hormoneNeuron-restrictive silencer factorCRH neuronsHypothalamic neuronsCRH expressionEarly life experiencesMiniature excitatory synaptic currentsHypothalamic CRH neuronsExcitatory synaptic currentsCRH gene expressionGlutamate vesicular transporterCRH gene transcriptionTranscriptional repressor neuron-restrictive silencer factorExcitatory innervationExperience-induced neuroplasticityInhibitory synapsesRat pupsExcitatory synapsesSynaptic currentsPersistent suppressionVesicular transportersCognitive functionNeuronsSilencer factorMaternal care
2006
Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque
Downs JL, Dunn MR, Borok E, Shanabrough M, Horvath TL, Kohama SG, Urbanski HF. Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque. Neurobiology Of Aging 2006, 28: 1286-1295. PMID: 16870307, DOI: 10.1016/j.neurobiolaging.2006.05.025.Peer-Reviewed Original ResearchConceptsLateral hypothalamic areaPoor sleep qualityLocus coeruleusNoradrenergic locus coeruleusSleep qualityNeuron numberRhesus macaquesAge-related decreaseTyrosine hydroxylase mRNAAge-related lossMale rhesus macaquesOrexin innervationOrexin neuronsOrexin neuropeptidesAge-related declineB immunoreactivityHypothalamic areaNeuronal changesElderly humansAxon densityLC contributeHydroxylase mRNANonhuman primatesOld animalsAdult animals