MicroRNA Predictors of Longevity in Caenorhabditis elegans 英文参考文献.docVIP

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MicroRNA Predictors of Longevity in Caenorhabditis elegans 英文参考文献.doc

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MicroRNA Predictors of Longevity in Caenorhabditis elegans 英文参考文献

MicroRNAPredictorsofLongevityinCaenorhabditis elegans ZacharyPincus,ThalyanaSmith-Vikos,FrankJ.Slack* DepartmentofMolecular,Cellular,andDevelopmentalBiology,YaleUniversity,NewHaven,Connecticut,UnitedStatesofAmerica Abstract Neither genetic nor environmental factors fully account for variability in individual longevity: genetically identical invertebrates in homogenous environments often experience no less variability in lifespan than outbred human populations.Suchvariabilityisoftenassumedtoresultfromstochasticityindamageaccumulationovertime;however,the identificationofearly-lifegeneexpressionstatesthatpredictfuturelongevitywouldsuggestthatlifespanisleastinpart epigenetically determined. Such ‘‘biomarkers of aging,’’ genetic or otherwise, nevertheless remain rare. In this work, we soughtearly-lifedifferencesinorganismal robustnessinunperturbed individualsandexaminedtheutilityofmicroRNAs, known regulators of lifespan, development, and robustness, as aging biomarkers. We quantitatively examined Caenorhabditis elegans reared individually in a novel apparatus and observed throughout their lives. Early-to-mid– adulthood measures of homeostatic ability jointly predict 62% of longevity variability. Though correlated, markers of growth/musclemaintenanceandofmetabolicby-products(‘‘agepigments’’)reportindependentlyonlifespan,suggesting that graceful aging is not a single process. We further identified three microRNAs in which early-adulthood expression patternsindividuallypredictupto47%oflifespandifferences.Thoughexpressionofeachincreasesthroughoutthistime, mir-71andmir-246correlatewithlifespan,whilemir-239anti-correlates.TwoofthesethreemicroRNA‘‘biomarkersofaging’’ actupstreamininsulin/IGF-1–likesignaling(IIS)andotherknownlongevitypathways,thusweinferthatthesemicroRNAs notonlyreportonbutalsolikelydeterminelongevity.Thus,fluctuationsinearly-lifeIIS,duetovariationinthesemicroRNAs andfromothercauses,maydetermineindividuallifespan. Citation: Pincus Z, Smith-Vikos T, Slack