0000000000122914

AUTHOR

John M. Sedivy

showing 4 related works from this author

Interventions to Slow Aging in Humans: Are We Ready?

2015

The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consens…

GerontologyAgingDisease onsetPrescription DrugsLongevityPsychological interventionReviewsBiologyAMP-Activated Protein KinasesGrowth hormoneAging; Anti-aging; Centenarians; Dietary restriction; Lifespan studies; Longevity gene; Longevity regulation; Cell Biology; AgingDietary interventionsBiological FactorsMicelongevity geneSettore BIO/13 - Biologia ApplicataAnimalsHumansSirtuinsProtein restrictionCentenarianInsulin-Like Growth Factor ILifespan studieCaloric RestrictionSettore MED/04 - Patologia GeneraleGeroscienceGene targetsRibosomal Protein S6 KinasesTOR Serine-Threonine Kinasesanti-agingdietary restrictionCell Biologydietary restriction ; lifespan studies ; longevity gene ; centenarians ; anti-aging ; longevity regulation ; aginglongevity regulation3. Good healthDietEnzyme ActivationGene Expression RegulationGrowth HormoneGenetics of agingcentenariansaging; anti-aging; centenarians; dietary restriction; lifespan studies; longevity gene; longevity regulationSignal Transductionlifespan studies
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DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progr…

2016

Abstract Aging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, a…

0301 basic medicineEpigenomicsCHROMATINCancer ResearchLIVERCancer Research; OncologyGene ExpressionSECRETORY PHENOTYPEHCV CORE PROTEINHistonesCell MovementProtein IsoformsCellular SenescenceEpigenomicsAged 80 and overMice KnockoutbiologyLiver NeoplasmsMETHYLATIONHep G2 CellsCANCERChromatinHistoneOncologyDNA methylationAzacitidineDisease ProgressionCell agingSTEM-CELLSSenescenceAdultEXPRESSIONCarcinoma HepatocellularArticle5-AZA-2'-DEOXYCYTIDINE03 medical and health sciencesCell Line TumorAnimalsHumansEpigeneticsCell ProliferationDNA Methylationbeta-GalactosidaseMolecular biologyMice Inbred C57BLMICE030104 developmental biologybiology.proteinCancer researchDNA hypomethylation
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O101 : Histone variant macroH2A1 orchestrates escape from hepatocyte senescence during ageing and cancer

2015

SenescenceHistonemedicine.anatomical_structureHepatologybiologyAgeingHepatocyteImmunologybiology.proteinCancer researchmedicineCancermedicine.diseaseJournal of Hepatology
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Histone Variant MacroH2A1 Marks Liver Aging and Orchestrates the Escape from Senescence Induced by DNA Hypomethylation in Hepatocellular Carcinoma

2015

The epigenetic basis of age-associated progression of liver diseases towards hepatocellular carcinoma (HCC) is unclear. MacroH2A1 is a variant of histone H2A1, present in the two isoforms, with fundamental roles in cell homeostasis. MacroH2A1 is a marker of senescence associated heterochromatic foci (SAHF) and synergizes with DNA demethylating chemotherapic agent 5-aza-2'-deoxycytidine (5-aza-dC) in silencing tumor suppressor genes in human fibroblasts. We show that protein levels of macroH2A1 isoforms are increased in the livers of old rodents and humans, and in human HCC tissue. Human HCC cells overexpressing macroH2A1 escape a 5-aza-dC-induced senescent phenotype, as determined by cell p…

SenescencebiologyCell growthCell cycleBiochemistryCell biologyHistoneGeneticsbiology.proteinGene silencingEpigeneticsMolecular BiologyGeneBiotechnologyDNA hypomethylation
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