OpinionTacklingAgingbyUsingmiRNAasaTargetandaToolWing-FuLai,1,2,*MarieLin,2andWing-TakWong1miRNAisaclassofshortnoncodingRNAthatregulatesgeneexpressionatthepost-transcriptionallevel.Evidenceofage-associatedchangesinmiRNAexpressionhasbeencollectedinmodelsrangingfromnematodestohumans;however,therehasbeenlittlediscussionofhowtoturnourknowledgeofmiRNAbiologyintoantiagingtherapy.ThisopinionarticleprovidesasnapshotofourcurrentunderstandingoftherolesofmiRNAinmodulatingtheagingprocess.WediscussmajorchemicaltechniquesformodifyingthemiRNAstructureaswellasdevelopingdeliverysystemsforintervention.Finally,technicalneedstobemetforbench-to-clinictranslationofmiRNA-basedinterventionsarehighlightedforfutureresearch.GeneticManipulationtoCombatAgingTheprocessofagingiscausednotonlybytheaccumulationofmutationsthathamperproperfunctioningofnormalgenesbutalsobyage-associatedalterationsattheepigeneticlevel.ThelatterresultsfromavarietyofchangesrangingfromDNAmethylationtochromatinremodeling.Formanyyears,diverseapproacheshavebeenreportedforgeneticmanipulation,includingtheuseofsmallinterferingRNA(siRNA)forgenesilencingandexpressionvectorsforgeneupregulation.Amongthese,microRNA(miRNA),whichisshortandnoncodingsingle-strandedRNAof~18–25ntinlength,displayspromisingapplicationpotentialbecauseitnotonlycanbeusedtomediategenesilencingbutalsoplaysregulatoryrolesindifferentbiologicalprocesses(e.g.,cellproliferation,apoptosis,development,anddifferentiation)[1–8].AlterationsinmiRNAexpressionarerelatednotonlytoage-relateddiseases[9,10]butalsotoagingperse[11–14].Thiswasdemonstratedbyanearlierstudyonperipheralbloodmononuclearcells(PBMCs,seeGlossary)whereacohortof21differentmiRNAmoleculeswerefoundtobeupregulatedduringhumanaging,and144miRNAmoleculesweresuppressed[15].ThisstudysuggestedthefeasibilityofusingmiRNAasanendogenoustherapeutictargetforthedevelopmentofantiaginginterventions.miRNAidentificationhastraditionallyemployedhybridization-basedarraymethods.Theefficiencyisfarfromsatisfactory,andthishasimpede...