2025
Proteoglycan-4 (PRG4) serum concentration is lower in aged mice, and genetic deficiency impacts survival probability, blood parameters, and bone during aging
Tanguay A, Menon N, Slavin E, Moody M, McEwen E, Jay G, Lorenzo J, Bartley J, Scanlon V, Deymier A, Schmidt T. Proteoglycan-4 (PRG4) serum concentration is lower in aged mice, and genetic deficiency impacts survival probability, blood parameters, and bone during aging. GeroScience 2025, 1-14. PMID: 40537697, DOI: 10.1007/s11357-025-01747-x.Peer-Reviewed Original ResearchWT miceCamptodactyly-arthropathy-coxa vara-pericarditisProteoglycan 4Aged wild typeYoung WT miceComplete blood countLoss-of-function mutationsAssessed clinical relevanceProteoglycan 4 geneBlood countAged miceSerum concentrationsAnti-fibroticRare diseaseBlood gasesClinical relevanceImmunomodulatory propertiesMiceWild typeBlood parametersYounger ageSurvival probabilitySex-dependentSerumLower survival probabilityMulticenter SPAN Trial of Fasudil in Ischemic Stroke.
Imai T, Morais A, Jin X, Qin T, Lamb J, Nagarkatti K, Chen M, Boisserand L, Patel R, Kumskova M, Chauhan A, Dhandapani K, Khan M, Kamat P, Shi Y, Cao S, Sanganahalli B, Mandeville J, Lyden P, Hess D, Leira E, Chauhan A, Aronowski J, McCullough L, Koehler R, Sansing L, Diniz M, Ayata C. Multicenter SPAN Trial of Fasudil in Ischemic Stroke. Stroke 2025 PMID: 40421536, DOI: 10.1161/strokeaha.125.050977.Peer-Reviewed Original ResearchSpontaneously Hypertensive RatsRho-associated kinase inhibitorHypertensive ratsAged miceActive treatment armsIschemic strokeModified intention-to-treat cohortKinase inhibitorsPrimary outcome end pointsIntention-to-treat cohortTest performanceEfficacy of fasudilPer-protocol populationOutcome end pointsMiddle cerebral artery occlusion modelHealthy young miceDiet-induced obese miceRodent modelsTrials NetworkTherapeutic profileFocal ischemic strokeTreatment armsYoung miceVehicle armSecondary outcomesEnhanced paracrine action of FGF21 in stromal cells delays thymic aging
Youm Y, Gliniak C, Zhang Y, Dlugos T, Scherer P, Dixit V. Enhanced paracrine action of FGF21 in stromal cells delays thymic aging. Nature Aging 2025, 5: 576-587. PMID: 39972172, PMCID: PMC12003152, DOI: 10.1038/s43587-025-00813-5.Peer-Reviewed Original ResearchThymic epithelial cellsThymic agingNaive CD8 T cellsCD8 T cellsAge-related thymic involutionT cell diversityThymic functionImmune dysfunctionThymic stromaT cellsThymic lymphopoiesisThymic involutionActions of FGF21Immune agingAged miceStromal cellsEpithelial cellsAged animalsCo-receptorHepatic overexpressionElevation of FGF21FGF21AgeCellsAdipocytesTime-restricted feeding reduces inflammatory markers and downregulates JAG1 and NICD protein levels in the liver of aged mice
Macêdo A, de Sousa Neto I, Antonio G, Gaspar R, de Lima R, Dias L, Vieira R, Muñoz V, Brunelli D, da Silva A, Cintra D, Ropelle E, Pauli J. Time-restricted feeding reduces inflammatory markers and downregulates JAG1 and NICD protein levels in the liver of aged mice. Nutrition 2025, 133: 112691. PMID: 39983606, DOI: 10.1016/j.nut.2025.112691.Peer-Reviewed Original ResearchConceptsRNA-seq datasetsNotch1 intracellular domainMitochondrial respirationTime-restricted feedingAged miceInflammatory markersAd libitum dietIntracellular domainHepatic mitochondrial respirationATP productionLiver mitochondrial respirationCellular longevityLiver of aged miceLibitum dietDisease Activity ScoreCompared to adult animalsNotch1 signalingProtein contentTime-restricted feeding protocolsUpregulation of Notch1Investigated metabolic parametersProtein levelsNotch1Adult miceCollagen fibers
2024
P-587 Salidroside improves the reproductive capacity of aged mice via improving oocyte mitochondrial function
Gu J, Hua R, Guo C, Hai Z, Xiao Y, Zhao P, Li Y, Su J, Wang T. P-587 Salidroside improves the reproductive capacity of aged mice via improving oocyte mitochondrial function. Human Reproduction 2024, 39: deae108.919. DOI: 10.1093/humrep/deae108.919.Peer-Reviewed Original ResearchOvarian agingIVM treatment groupsGV oocytesFemale miceTreatment groupsAged miceDays of in vivo treatmentOocyte mitochondrial functionIn vivoOvarian reserve functionIn vitroTreatment of ovarian agingFunction of miceMitochondrial functionFollicle reserveMII oocytesTherapeutic effect of salidrosideAged oocytesParthenogenetic activationC57/B6 miceOocyte qualityMaternal ageParthenogenetic embryosWider implicationsSalidroside supplementationCaloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice
Rinne C, Soultoukis G, Oveisi M, Leer M, Schmidt-Bleek O, Burkhardt L, Bucher C, Moussa E, Makhlouf M, Duda G, Saraiva L, Schmidt-Bleek K, Schulz T. Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice. Frontiers In Endocrinology 2024, 15: 1394263. PMID: 38904042, PMCID: PMC11188307, DOI: 10.3389/fendo.2024.1394263.Peer-Reviewed Original ResearchConceptsBone marrow adipose tissueTrabecular bone lossAged miceCaloric restrictionBone lossEndocrine profileMale C57BL6J miceCardio-metabolic diseasesTime of CRAge-matched littermatesBiochemical lipid profilesAssess bone microstructureFree food accessC57BL6J miceBone healthYoung miceContext of agingMale miceDietary interventionNutritional interventionAnatomical localizationLipid profileAdipogenic gene expressionBone dysfunctionTrabecular bone structureiGATE analysis improves the interpretability of single-cell immune landscape of influenza infection
Hill B, Zak A, Raja S, Bugada L, Rizvi S, Roslan S, Nguyen H, Chen J, Jiang H, Ono A, Goldstein D, Wen F. iGATE analysis improves the interpretability of single-cell immune landscape of influenza infection. JCI Insight 2024, 9: e172140. PMID: 38814732, PMCID: PMC11383363, DOI: 10.1172/jci.insight.172140.Peer-Reviewed Original ResearchInfluenza infectionImmune cell typesCourse of influenza infectionDefective T cell responsesSurvival of C57BL/6 miceCell typesDecreased IL-10 expressionEffect of host genetic backgroundT cell responsesGenetic backgroundTime-of-flight (CyTOFIL-10 expressionInflammatory cell typesCells in silicoHost genetic backgroundC57BL/6 miceAged miceMouse lungHost genotypeInfection susceptibilityHost factorsEffects of ageMiceHealth burdenInfectionPublisher Correction: Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice
Tyrrell D, Wragg K, Chen J, Wang H, Song J, Blin M, Bolding C, Vardaman D, Giles K, Tidwell H, Ali M, Janappareddi A, Wood S, Goldstein D. Publisher Correction: Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice. Nature Aging 2024, 4: 1166-1166. PMID: 38789547, DOI: 10.1038/s43587-024-00653-9.Peer-Reviewed Original ResearchThe Benjamin Button effect on stem cells: Reversing the clock on aging immunity.
Conde L, Lucas C. The Benjamin Button effect on stem cells: Reversing the clock on aging immunity. Science Immunology 2024, 9: eadq0013. PMID: 38701191, DOI: 10.1126/sciimmunol.adq0013.Peer-Reviewed Original ResearchDisruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells
Cozzolino M, Ergun Y, Ristori E, Garg A, Imamoglu G, Seli E. Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells. Aging 2024, 16: 2047-2060. PMID: 38349865, PMCID: PMC10911389, DOI: 10.18632/aging.205543.Peer-Reviewed Original ResearchConceptsCaseinolytic peptidase PMitochondrial unfolded protein responseUnfolded protein responseTelomere integrityProtein responseGermline deletionSomatic cellsSomatic agingSomatic cell divisionDouble-stranded DNA breaksAged miceTelomere shorteningAssociated with cellular senescenceTelomeric regionsProtein homeostasisAccelerated follicular depletionChromosome stabilityCell divisionMtUPRDNA breaksTelomereAging phenotypesCellular senescenceFollicular depletionMouse oocytes
2023
Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice
Tyrrell D, Wragg K, Chen J, Wang H, Song J, Blin M, Bolding C, Vardaman D, Giles K, Tidwell H, Ali M, Janappareddi A, Wood S, Goldstein D. Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice. Nature Aging 2023, 3: 1576-1590. PMID: 37996758, PMCID: PMC11924142, DOI: 10.1038/s43587-023-00515-w.Peer-Reviewed Original ResearchConceptsT cellsMemory CD8Aged miceAtherosclerotic plaquesDepletion of CD8Effector memory subsetsStrong risk factorT cell activationEnhanced atherosclerosisSplenic CD8Adoptive transferDonor miceMemory subsetsRecipient miceRisk factorsCD8Therapeutic targetCell activationAtherosclerosisSingle-cell RNA sequencingMiceTranscriptomic signaturesAtherogenesisPlaquesRNA sequencingAge-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics
Wang Y, Deng W, Lee D, Yan L, Lu Y, Dong S, Huntoon K, Antony A, Li X, Ye R, Zhao Y, Zhao F, Schrank B, Ha J, Kang M, Yang M, Gong P, Lorenzi P, Tan L, Gallup T, Tang S, Yang Z, Li J, Sanford N, Wang H, Kim B, Jiang W. Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics. Nature Nanotechnology 2023, 19: 255-263. PMID: 37723279, DOI: 10.1038/s41565-023-01502-3.Peer-Reviewed Original ResearchConceptsCancer nanotherapeuticsCancer nanomedicineScavenger receptor MARCOPhagocytic clearanceUptake of nanoparticlesAntitumour responseTumor deliveryTherapeutic blockadeAntitumour efficacyAge-Associated DecreaseHepatic phagocytesAntitumour effectsYoung miceHepatic macrophagesAged miceTreatment outcomesTreat multiple human diseasesProtein level analysisHepatic uptakeAge-related declineNon-human primatesNanotherapeuticsMiceNanomedicinePhagocytic uptakeA Treg-specific long noncoding RNA maintains immune-metabolic homeostasis in aging liver
Ding C, Yu Z, Sefik E, Zhou J, Kaffe E, Wang G, Li B, Flavell R, Hu W, Ye Y, Li H. A Treg-specific long noncoding RNA maintains immune-metabolic homeostasis in aging liver. Nature Aging 2023, 3: 813-828. PMID: 37277640, DOI: 10.1038/s43587-023-00428-8.Peer-Reviewed Original ResearchConceptsAged miceLiver diseaseLiver microenvironmentAge-related liver diseasesYin Yang 1Liver immune microenvironmentRegulatory T cellsTreg-specific deletionPotential therapeutic targetMitochondrial functionYang 1Treg apoptosisTreg homeostasisTreg cellsTreg functionImmune microenvironmentLiver fibrosisMetabolic dysfunctionOptimal mitochondrial functionYoung miceT cellsLiver cancerTherapeutic targetAged liverLong noncoding RNAThe age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques
Kabir I, Zhang X, Dave J, Chakraborty R, Qu R, Chandran R, Ntokou A, Gallardo-Vara E, Aryal B, Rotllan N, Garcia-Milian R, Hwa J, Kluger Y, Martin K, Fernández-Hernando C, Greif D. The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques. Nature Aging 2023, 3: 64-81. PMID: 36743663, PMCID: PMC9894379, DOI: 10.1038/s43587-022-00342-5.Peer-Reviewed Original ResearchConceptsAtherosclerotic plaquesBone marrowSmooth muscle-derived cellsSMC progenitorsAtherosclerotic plaque cellsSmooth muscle cell progenitorsPredominant risk factorCause of deathNovel therapeutic strategiesTNF receptor 1Muscle-derived cellsAged bone marrowAged BMEffect of agePlaque burdenAged miceRisk factorsTumor necrosisTherapeutic strategiesPlaque cellsMyeloid cellsReceptor 1Integrin β3Cell progenitorsAtherosclerosisHistone deacetylase inhibitors mitigate antipsychotic risperidone-induced motor side effects in aged mice and in a mouse model of Alzheimer’s disease
Rodriguez G, Fisher D, McClarty B, Montalvo-Ortiz J, Cui Q, Chan C, Dong H. Histone deacetylase inhibitors mitigate antipsychotic risperidone-induced motor side effects in aged mice and in a mouse model of Alzheimer’s disease. Frontiers In Psychiatry 2023, 13: 1020831. PMID: 36684015, PMCID: PMC9852991, DOI: 10.3389/fpsyt.2022.1020831.Peer-Reviewed Original ResearchMotor side effectsSevere neuropsychiatric symptomsAged miceSide effectsHDAC inhibitorsNeuropsychiatric symptomsDementia patientsHistone deacetylase inhibitor valproic acidAtypical antipsychotic risperidoneTypical antipsychotic haloperidolAntipsychotic drug targetsGreater side effectsInhibitor valproic acidHistone deacetylase inhibitorsAge-related sensitivityEpigenetic alterationsAtypical antipsychoticsD2R expressionAntipsychotic haloperidolLabel useAntipsychotic risperidoneAntipsychotic drugsMouse modelValproic acidClinical practice
2022
Aging reduces ABHD5 protein content in the adipose tissue of mice: The reversal effect of exercise
Brícola R, Cordeiro A, Crisol B, Braga R, de Melo D, Rocha M, Gaspar R, Nakandakari S, Silva V, Anaruma C, Katashima C, Canciglieri R, Munõz V, Pavan I, Pinto A, Simabuco F, da Silva A, Moura L, Pauli J, Cintra D, Ropelle E. Aging reduces ABHD5 protein content in the adipose tissue of mice: The reversal effect of exercise. Cell Biochemistry And Function 2022, 41: 128-137. PMID: 36515301, DOI: 10.1002/cbf.3770.Peer-Reviewed Original ResearchConceptsAged miceAdipose tissueControl of lipolysisHigh-intensity interval trainingSubcutaneous white adipose tissueExperimental mouse modelAdipose tissue metabolismWhite adipose tissueMessenger RNA levelsInterval trainingMouse modelTissue metabolismLipolytic pathwayMiceRNA levelsProtein levelsScWATTranscriptomic analyzesReversal effectTissueExerciseSignificant hallmarkLipolysisABHD5Lipolytic activity
2021
Leveraging ageing models of pulmonary fibrosis: the efficacy of nintedanib in ageing
Kato K, Shin YJ, Palumbo S, Papageorgiou I, Hahn S, Irish JD, Rounseville SP, Krafty RT, Wollin L, Sauler M, Hecker L. Leveraging ageing models of pulmonary fibrosis: the efficacy of nintedanib in ageing. European Respiratory Journal 2021, 58: 2100759. PMID: 34531276, PMCID: PMC8613836, DOI: 10.1183/13993003.00759-2021.Peer-Reviewed Original ResearchConceptsEfficacy of nintedanibIdiopathic pulmonary fibrosisAged miceLung fibrosisPulmonary fibrosisElderly patientsLung functionPre-clinical efficacy studiesAged animal modelsIPF clinical trialsVital capacity declineAverage patient ageVehicle-treated miceVehicle-treated groupEffect of nintedanibSeverity of fibrosisDevelopment of fibrosisTotal lung collagenSimilar extentNintedanib treatmentLung injuryPatient ageIPF diagnosisClinical efficacyFibrosis severityIL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2
Goldberg EL, Shchukina I, Youm YH, Ryu S, Tsusaka T, Young KC, Camell CD, Dlugos T, Artyomov MN, Dixit VD. IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2. Cell Metabolism 2021, 33: 2277-2287.e5. PMID: 34473956, PMCID: PMC9067336, DOI: 10.1016/j.cmet.2021.08.004.Peer-Reviewed Original ResearchConceptsOld miceType 2 innate lymphoid cellsInnate lymphoid cellsTissue-resident cellsCore body temperatureAdoptive transferIL-33ILC2 numbersTissue inflammationAged miceImmunometabolic responsesMetabolic impairmentLymphoid cellsDietary restrictionImmune systemILC2Functional defectsMiceBody temperatureFailureCellsInflammationTranscriptomic analysisInfectionStress responseExogenous inter-α inhibitor proteins prevent cell death and improve ischemic stroke outcomes in mice
McCullough LD, Roy-O’Reilly M, Lai YJ, Patrizz A, Xu Y, Lee J, Holmes A, Kraushaar DC, Chauhan A, Sansing LH, Stonestreet BS, Zhu L, Kofler J, Lim YP, Venna VR. Exogenous inter-α inhibitor proteins prevent cell death and improve ischemic stroke outcomes in mice. Journal Of Clinical Investigation 2021, 131: e144898. PMID: 34580244, PMCID: PMC8409590, DOI: 10.1172/jci144898.Peer-Reviewed Original ResearchConceptsInter-α inhibitor proteinsIschemic strokeStroke outcomeStroke modelComplement activationBeneficial effectsMultiple stroke modelsNeutralization of histonesPost-stroke administrationIschemic stroke outcomeExperimental ischemic strokeIschemic stroke patientsExperimental stroke modelsModel of sepsisPotential therapeutic candidateExcess complement activationIaIp levelsStroke onsetStroke patientsProinflammatory cytokinesAged miceExtracellular histonesClinical relevanceTherapeutic candidateTherapeutic efficacyKetogenic 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
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