2024
Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk
Brandhorst S, Levine M, Wei M, Shelehchi M, Morgan T, Nayak K, Dorff T, Hong K, Crimmins E, Cohen P, Longo V. Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nature Communications 2024, 15: 1309. PMID: 38378685, PMCID: PMC10879164, DOI: 10.1038/s41467-024-45260-9.Peer-Reviewed Original ResearchConceptsMultiple cardiometabolic risk factorsAssociated with reduced insulin resistanceCardiometabolic risk factorsFasting-mimicking dietImmune system agingRandomized clinical trialsAnalysis of blood samplesAutoimmune cellsBiological ageClinical trialsReduce inflammationMarker changesRisk factorsHepatic fatInsulin resistanceAdult study participantsBlood samplesNormal cellsWeight lossReducing biological ageBiomarker of biological agingDamaged cellsStudy participantsDisease riskAge
2023
OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases
Sturm G, Karan K, Monzel A, Santhanam B, Taivassalo T, Bris C, Ware S, Cross M, Towheed A, Higgins-Chen A, McManus M, Cardenas A, Lin J, Epel E, Rahman S, Vissing J, Grassi B, Levine M, Horvath S, Haller R, Lenaers G, Wallace D, St-Onge M, Tavazoie S, Procaccio V, Kaufman B, Seifert E, Hirano M, Picard M. OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases. Communications Biology 2023, 6: 22. PMID: 36635485, PMCID: PMC9837150, DOI: 10.1038/s42003-022-04303-x.Peer-Reviewed Original ResearchMeSH KeywordsDNA, MitochondrialHumansLongevityMitochondriaMitochondrial DiseasesOxidative PhosphorylationConceptsIntegrated stress responseOXPHOS defectsMitochondrial diseaseCellular energy expenditureMitochondrial DNA instabilityPatient-derived fibroblastsMitochondrial oxidative phosphorylationCell divisionExtracellular secretionOxidative phosphorylationStress responseDNA instabilityMechanistic basisEnergetic costEpigenetic agingGeneral mechanismOXPHOSBiological agingExcess energy expenditurePotential mechanismsEnergy expenditureCellsMulti-system disorderMetabokinesRNAseq
2021
Extending human healthspan and longevity: a symposium report
DeVito LM, Barzilai N, Cuervo AM, Niedernhofer LJ, Milman S, Levine M, Promislow D, Ferrucci L, Kuchel GA, Mannick J, Justice J, Gonzales MM, Kirkland JL, Cohen P, Campisi J. Extending human healthspan and longevity: a symposium report. Annals Of The New York Academy Of Sciences 2021, 1507: 70-83. PMID: 34498278, PMCID: PMC10231756, DOI: 10.1111/nyas.14681.Peer-Reviewed Original ResearchConceptsAge-related diseasesEarly-stage clinical trialsField of geroscienceReduction of morbidityBiological agingEnd of lifeClinical trialsNovel agentsClinical developmentGeroscience hypothesisFDA approvalDrug evaluationMultiple disordersTherapyDiseaseSymposium reportConcept studyHuman healthspanHealthspanAging processSignificant barriersMorbidityDysfunctionAgingTrials
2018
An epigenetic biomarker of aging for lifespan and healthspan
Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, Hou L, Baccarelli AA, Stewart JD, Li Y, Whitsel EA, Wilson JG, Reiner AP, Aviv A, Lohman K, Liu Y, Ferrucci L, Horvath S. An epigenetic biomarker of aging for lifespan and healthspan. Aging 2018, 10: 573-591. PMID: 29676998, PMCID: PMC5940111, DOI: 10.18632/aging.101414.Peer-Reviewed Original ResearchConceptsEpigenetic biomarkersDNA damage responseTranslational machineryMitochondrial signatureTranscriptional analysisDamage responseNew epigenetic biomarkersMultiple tissuesNovel CpGsInterferon pathwayHealthspanSorted cellsImportant pathwayPathwayCellsLifespanActivationBiological ageDiverse outcomesDNAm PhenoAgeMachineryMajor goalTissueCpGGeroscience
2015
A Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans
Levine ME, Crimmins EM. A Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans. The Journals Of Gerontology Series A 2015, 71: 703-712. PMID: 26355015, PMCID: PMC4888382, DOI: 10.1093/gerona/glv141.Peer-Reviewed Original ResearchConceptsFunctional interaction networkSingle nucleotide polymorphismsStress resistanceNucleotide polymorphismsInteraction networksGenome-wide association studiesPathway analysisAssociation studiesPolygenic risk scoresNetworks AssociatedBiological networksHuman longevityUnique phenotypeHuman agingGenesPolymorphismLongevityPhenotypeInnate resilienceRisk scoreAge 52Threefold increasePathwayWeighted polygenic risk scoreResistance
2014
Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population
Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK, Wei M, Cohen P, Crimmins EM, Longo VD. Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population. Cell Metabolism 2014, 19: 407-417. PMID: 24606898, PMCID: PMC3988204, DOI: 10.1016/j.cmet.2014.02.006.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsBreast NeoplasmsCarrier ProteinsCross-Sectional StudiesDiabetes MellitusDiet, Protein-RestrictedFemaleFollow-Up StudiesHumansInsulin-Like Growth Factor ILongevityMaleMelanomaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMiddle AgedNeoplasmsProportional Hazards ModelsSignal TransductionConceptsHigh protein intakeOverall mortalityProtein intakeCancer death riskProgression of breastLow protein intakeLow-protein dietHigh protein consumptionDiabetes mortalityAge-related diseasesDeath riskProtein restrictionIGF-1Melanoma tumorsMortalityMouse studiesOlder populationProtein dietOlder adultsIntakeMajor reductionProtein consumptionCancerLow proteinAge