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 predictorLungMortalityAgeAdiponectin preserves metabolic fitness during aging
Li N, Zhao S, Zhang Z, Zhu Y, Gliniak CM, Vishvanath L, An YA, Wang MY, Deng Y, Zhu Q, Shan B, Sherwood A, Onodera T, Oz OK, Gordillo R, Gupta RK, Liu M, Horvath TL, Dixit VD, Scherer PE. Adiponectin preserves metabolic fitness during aging. ELife 2021, 10: e65108. PMID: 33904399, PMCID: PMC8099426, DOI: 10.7554/elife.65108.Peer-Reviewed Original ResearchConceptsAdiponectin null miceSystemic insulin sensitivityInsulin sensitivityNull miceAge-related glucoseRole of adiponectinLipid metabolism disordersHigh-fat dietTransgenic mouse modelAdiponectin levelsTissue inflammationMetabolism disordersClinical studiesMouse modelAdiponectinMice displayMetabolic fitnessOverexpression modelPositive associationMiceMedian lifespanHealthspanDirect effectEssential regulatorAging processAge‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates
Datta D, Leslie SN, Wang M, Morozov YM, Yang S, Mentone S, Zeiss C, Duque A, Rakic P, Horvath TL, van Dyck C, Nairn AC, Arnsten AFT. Age‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates. Alzheimer's & Dementia 2021, 17: 920-932. PMID: 33829643, PMCID: PMC8195842, DOI: 10.1002/alz.12325.Peer-Reviewed Original ResearchConceptsTau pathologyCalcium leakTau phosphorylationNeuronal firingAlzheimer's diseaseEarly tau phosphorylationPyramidal cell dendritesSporadic Alzheimer's diseasePrimary cortical neuronsPotential therapeutic targetCognitive performanceAge-related reductionMacaque dorsolateral prefrontal cortexDorsolateral prefrontal cortexNon-human primatesCalcium dysregulationCell dendritesCortical neuronsCalcium-binding proteinsAD biomarkersPathology markersTherapeutic targetAnimal modelsAged monkeysPrefrontal cortex
2019
Mitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging
Zhang M, Bener MB, Jiang Z, Wang T, Esencan E, Scott R, Horvath T, Seli E. Mitofusin 2 plays a role in oocyte and follicle development, and is required to maintain ovarian follicular reserve during reproductive aging. Aging 2019, 11: 3919-3938. PMID: 31204316, PMCID: PMC6628992, DOI: 10.18632/aging.102024.Peer-Reviewed Original ResearchConceptsMitofusin 2Key regulatory proteinsImpaired oocyte maturationFollicle developmentMitochondrial fusionRegulatory proteinsEndoplasmic reticulumMitochondrial dysfunctionTargeted deletionOocyte maturationOocytesReproductive agingFemale subfertilityOocyte qualityOvarian follicular reserveTelomeresMitochondriaMetabolic milieuProteinReticulumDeletionFusionPhenotypeApoptosisMaturationMitochondrial 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
2018
Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos
Wang T, Babayev E, Jiang Z, Li G, Zhang M, Esencan E, Horvath T, Seli E. Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging, for oocyte competence, and development of pre‐implantation embryos. Aging Cell 2018, 17: e12784. PMID: 29851234, PMCID: PMC6052477, DOI: 10.1111/acel.12784.Peer-Reviewed Original ResearchConceptsMitochondrial unfolded protein responseUnfolded mitochondrial proteinsCaseinolytic peptidase PAbsence of ClpPUnfolded protein responsePre-implantation embryosExpression of genesOocyte mitochondrial functionTwo-cell embryosProtein homeostasisMTOR inhibitor rapamycinMitochondrial proteinsOocyte competenceClpPProtein responseInhibitor rapamycinMitochondrial functionP-Akt473P-S6KOvarian follicular reserveSmall mitochondriaMTOR pathway activationPathway activationEmbryosP-S6
2016
Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity
Babayev E, Wang T, Szigeti-Buck K, Lowther K, Taylor HS, Horvath T, Seli E. Reproductive aging is associated with changes in oocyte mitochondrial dynamics, function, and mtDNA quantity. Maturitas 2016, 93: 121-130. PMID: 27523387, PMCID: PMC5064871, DOI: 10.1016/j.maturitas.2016.06.015.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesUnfolded protein response genesProtein response genesMitochondrial DNAMitochondrial dynamicsMitochondrial stressResponse genesMammalian reproductionMitochondria morphologyStressful conditionsMitochondrial changesMitochondriaROS levelsMtDNA levelsElevated expressionMtDNA quantityOxygen speciesOocytesGenesMature oocytesNumerous aspectsExpressionReproductive agingMII oocytesFollicle-enclosed oocytesProlongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution
Youm YH, Horvath TL, Mangelsdorf DJ, Kliewer SA, Dixit VD. Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 1026-1031. PMID: 26755598, PMCID: PMC4743827, DOI: 10.1073/pnas.1514511113.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationAge-related thymic involutionCaloric restrictionFGF21 functionThymic involutionThymic agingHormone fibroblast growth factor 21Peripheral T-cell diversityThymic T-cell exportFibroblast growth factor 21Diverse T cell repertoireCortical thymic epithelial cellsLow immune competenceT cell frequenciesStem cell transplantationGrowth factor 21Naïve T cellsMiddle-aged miceT cell repertoireT cell diversityThymic stromal cellsT cell exportThymic epithelial cellsBrown adipose tissueEarly thymocyte progenitors
2013
Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions
Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang YY, Lee H, Srinivas P, Gao XB, Suyama S, Langer T, Mann JJ, Horvath TL, Bonnin A, Karsenty G. Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions. Cell 2013, 155: 228-241. PMID: 24074871, PMCID: PMC3864001, DOI: 10.1016/j.cell.2013.08.042.Peer-Reviewed Original ResearchConceptsOsteoblast-derived hormone osteocalcinBrain developmentBone-derived signalsBlood-brain barrierFetal brain developmentInfluences brain developmentBone massNeuronal apoptosisMonoamine neurotransmittersGABA synthesisMemory deficitsNeuroanatomical defectsOffspring poolPostnatal functionMaternal genotypeMetabolic functionsOsteocalcinPowerful regulationBrainMaternal influenceRegulationBrainstemPregnancyHippocampusMidbrain
2009
The role of mitochondrial uncoupling proteins in lifespan
Dietrich MO, Horvath TL. The role of mitochondrial uncoupling proteins in lifespan. Pflügers Archiv - European Journal Of Physiology 2009, 459: 269-275. PMID: 19760284, PMCID: PMC2809791, DOI: 10.1007/s00424-009-0729-0.Peer-Reviewed Original ResearchConceptsMitochondrial inner membraneCellular biochemical reactionsMitochondrial uncoupling proteinProduction of ATPCellular functionsInner membraneSpecialized proteinsBreakdown of lipidsMain organellesExcess of ROSPhysiological uncouplingOxidative phosphorylationUncoupling proteinAdenosine triphosphateOxygen reactive speciesROS productionProteinEnergetic substratesBiochemical reactionsCellular damageMitochondriaROSIntermediate substrateUCPShed light
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
2004
Sex differences in adult suprachiasmatic nucleus neurons emerging late prenatally in rats
Abizaid A, Mezei G, Sotonyi P, Horvath TL. Sex differences in adult suprachiasmatic nucleus neurons emerging late prenatally in rats. European Journal Of Neuroscience 2004, 19: 2488-2496. PMID: 15128402, DOI: 10.1111/j.0953-816x.2004.03359.x.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnalysis of VarianceAnimalsAnimals, NewbornArginine VasopressinBromodeoxyuridineCalbindin 1CalbindinsCell CountEmbryo, MammalianFemaleGeniculate BodiesGlial Fibrillary Acidic ProteinImmunohistochemistryMaleNeuronsNeuropeptide YPregnancyPrenatal Exposure Delayed EffectsRatsRats, Sprague-DawleyS100 Calcium Binding Protein GSex CharacteristicsSuprachiasmatic NucleusTestosterone PropionateConceptsSuprachiasmatic nucleusGonadal steroidsFemale ratsLate gestationSex differencesPregnant female ratsVasoactive intestinal peptideGestational day 18Postnatal day 60BrdU-labeled cellsCalbindin-D28KSuprachiasmatic nucleus neuronsCircadian rhythmIntestinal peptideNucleus neuronsDouble immunocytochemistryGonadal functionTestosterone propionateBrain sectionsRat fetusesDay 18Day 60Cell groupsRatsSCN cells
2003
Estrogen, synaptic plasticity and hypothalamic reproductive aging
Hung AJ, Stanbury MG, Shanabrough M, Horvath TL, Garcia-Segura LM, Naftolin F. Estrogen, synaptic plasticity and hypothalamic reproductive aging. Experimental Gerontology 2003, 38: 53-59. PMID: 12543261, DOI: 10.1016/s0531-5565(02)00183-3.Peer-Reviewed Original ResearchConceptsConstant estrusReproductive agingEstrogen exposureMale ratsAnti-oxidant vitamin EEarly estrogen exposureArcuate nucleus neuronsHypothalamic arcuate nucleus neuronsConstant vaginal estrusHypothalamic failureEstradiol exposureGonadotrophin surgeOvarian estrogenArcuate nucleusConstant diestrusNucleus neuronsOvarian failureElevated estradiolPerikaryal membraneFemale ratsPerinatal periodTesticular androgensRat brainSex steroidsHormonal factors