Chronic stress

SpecialIssueR405Theallocationprinciplehasalsobeentestedusingmoredirectapproaches,involvingnaturalselectioninthelaboratory.Suchexperimentshavearichhistory,probablybeginningwiththeexperimentsofReverendWilliamH.Dallinger,acontemporaryofDarwinwhowaslikelybestknownforhisdetailedaccountsofprotozoanlifecycles,whichhelpeddispelawidelyheldviewatthetimethatlifearosedenovo,fromnothing.EncouragedbyDarwin,Dallingersoughttotestthetheoryofevolutionvianaturalselectionbysubjectingprotozoatoincreasinglyhighertemperaturestoseeiftheywouldadapttothenewconditions.Todothis,Dallingerhadtoconstructanincubationapparatusthatallowedprecisecontroloftemperature(Figure2).Inanexperimentthatlastedsevenyears,Dallingerwasabletoshowthatanorganismoriginatingfromanenvironmentwherethetemperatureis60°Fcould,amazingly,becomeadaptedto158°F.Darwin’sownreactiononhearingabouttheworkspeakstoitsimportance:“Ididnotknowthatyouwereattendingtothemutationofthelowerorganismsunderchangedconditionsoflife;andyourresults,Ihavenodoubt,willbeextremelycuriousandvaluable.Thefactwhichyoumentionabouttheirbeingadaptedtocertaintemperatures,butbecominggraduallyaccustomedtomuchhigherones,isveryremarkable.Itexplainstheexistenceofalgaeinhotsprings.”Interestingly,whenDallingerplacedtheadaptedprotozoabackat60°F,thisprovedlethal,anobservationthatwouldseemconsistentwiththeallocationprinciple.Thetraditionofexperimentalevolutioncontinuedintothe20thcenturywithworkonanumberofotherorganismschoseninpartfortheirrelativelyshortgenerationtimes,suchasDrosophila.ButtheDallingerexperimenthasaparticularlyclosecorollaryinafruitfullineofresearchinitiatedbyRichardLenskiandcolleagues,whohavebeenperformingalong-termevolutionexperimentonbacteriaexposedtodifferent,sometimesvaryingconditions.Initiatedin1988,theexperimenthasnowcrossedthe50,000generationmark.Theworkhasaddressedanumberofquestions,but,ofrelevancetoDallingerandallocationtheory,BennettandLenskiplaced20differentlinesofEscherichiacoliat20°Cfor2,000generationsandthenaskedhowtheyfaredat40°C[3].Ingeneral,whilefitnessincreasedat20°C,itbecamereducedat40°C,consistentwithallocationtheory.Buttheeffectwasnotuniversalasseverallinesshowednolossoffitnessatthehighertemperatureand,inonecase,evengreaterfitness.Whatwecantakeawayfromthesestudiesisthatwearestartingtoseepatternsthatinsomecasesareconsistentwithtradeoffsoccurringoverthecourseofevolution,butthisiscertainlynotagiven.Insomecases,thereisapparentlynopenaltyformaintainingadaptationsthatarenolongerofuse.Itwillbeinterestingtocontinuetogatherdatafrommorespeciesusingdifferentstressesandselectionregimestoseeifthesepatternsholdup.And,ofcourse,we’llwanttobetterunderstandthegeneticbasisofadaptationtostresssothatwecanstarttounderstandthemechanismsandwhy,insomecases,atradeoffmaybenecessaryasorganismsadapttostressfulenvironments.Comingfullcirclethen,wecanseethattheterm‘stress’canbebroadlyconstrued,functioningasanintegralpartofthelifecyclebutmoreoftenmanifestingasanenvironmentalinsult,inresponsetowhichhomeostaticmechanismsarise.Stressresponsesalsooperateatvariousscales,fromrapidmillisecondresponsesthatrestorehomeostasis,totheadaptationoforganismsoverevolutionarytimescales.Thereachofstressintosomanyfacetsofbiologyissuchthatwealmosttakeitforgranted.Itseemsappropriatethenthatwedevotethisspecialissuetothetopicandexplorestressinitsvariousforms.Enjoy!References1.Zahradka,K.,Slade,D.,Bailone,A.,Sommer,S.,Averbeck,D.,Petranovic,M.,Lindner,A.B.,andRadman,M.(2006).ReassemblyofshatteredchromosomesinDeinococcusradiodurans.Nature443,569–573.2.Huey,R.B.,andKingsolver,J.G.(1993).Evolutionofresistancetohightemperatureinectotherms.Am.Nat.142,S21–S46.3.Bennett,A.F.,andLenski,R.E.(2007).Anexperimentaltestofevolutionarytrade-offsduringtemperatureadaptation.Proc.Natl.Acad.Sci.USA104,S8649–S8654.CyrusMartinSeniorScientificEditor,CurrentBiologyChronicstressmeanswe’realwaysonthehuntStressresponsesthatevolvedforoccasionaldangeroussituationscanmakeusillwhentheybecomechronic.Butwhydoweperceiveourrelativelysafelivesasstressfulandwhatcanwedotoavoidtheassociateddangers?MichaelGrossinvestigates.Lifeformanymammalianspeciesisalongstringofhappydaysspentgrazinginthesavannah—brutallyinterruptedbyshortmomentswhenapredatorshowsupandtheyhavetorunfortheirlives.Herbivores,likethehorsesandtheirrelatives,haveevolvedarangeofcharacteristicsespeciallyfortheseshortmomentsofflight,fromtheirfast-runninglegsthroughtotheabilitytokeepcoolbyabundantsweating(sharedwithhumansbutotherwiserareintheanimalkingdom).Thesituationissimilarforthehunters,albeitreversed.Lionsspendmuchoftheirdaysleepinganddigesting,interruptedbyshortperiodsofhuntingfleet-footedprey.Theirsurvivalalsodependsonthisshortperiodofexertion,astheywouldstarveiftheyfailedtohuntsuccessfully.Inbothcases,twosystemsareactivated.Thesympatheticnervoussystempreparesthebody’sorgansfor‘fightorflight’responses,increasingoxygenintake,bloodpressure,heartrate,andmuscleactivity,whileshuttingdownthedigestivesystem.Additionally,ageneralhormoneresponseisactivatedthatmakesextraenergyavailablefortheshort-termuseandsharpensthesenses.Specifically,theHPAaxis(hypothalamus,pituitarygland,andadrenalcortex)releaseshormonesincludingcorticosteroidsandthecatecholaminesadrenaline(epinephrine)andnoradrenaline,whichenhancemetabolicactivity(increasingbloodsugar),andimprovealertnessandattention.Thesetwoprocesses,nervousandendocrine(hormonal),worktogethertoformthephysiologicalstressresponse.FeatureCurrentBiologyVol24No10R406Reddanger:Thephysiologicalstressresponseisgoodandimportantindangeroussituationswhererapidreactionsareneeded,butdamagingifitbecomesachronicelementofeverydaylife.PsychologistCatherineFranssenreportsthatextremesportslikeskydivingorrockclimb-ingmayhelptoputthetrivialproblemsofmodernlifeintoperspective.ThepictureshowstheRedDevilsFreefallTeam.(Photo:©CrownCopyright.UsedwithpermissionfromTheRedDevilsFreefallTeam(www.reddevilsonline.com).)Humanssharetheseverysameresponseswithothermammals,andtheycanalsobelife-savingforusindangeroussituations.However,ifthehormonalresponseisusedtoooften,andstaysturnedonfortoolong,theemergencyprogrammeturnsintochronicstress,andthishasawiderangeofdamagingeffectsthatcanleadtofataldiseases,includingheartfailure.Wearefacingsomethingofaparadoxhere.Aslongaswedon’tliveinwarzonesorengageinextremeadventures,ourlivesaresaferthantheyeverwereinhumanhistoryandtherearenopredatoryspeciesleftthatweshouldfear,apartfromourown.Sowhyhasstressbecomeadefiningfeatureofmodernlifeandamajorhealthconcern?CulturalhistoryofstressThedefinitionofbiologicalstressasasituationanindividualcanbein,asopposedtotheconceptfromphysics,whichdescribestheexternalforcesthatmightinduceastrain,canbetracedbacktotheworkoftheHungarianendocrinologistHansSelye(1907–1982).Inthe1960s,itbecameawidelyinvestigatedconceptinpsychology,andbythe1970sitspreadintopopularusage,alongwithassociatedtermssuchasburnoutandmidlifecrisis.Researchersinvestigatedcausesofstressintheenvironmentalconditionsofmodernlife,includingtheworkenvironment,thecommuterexperienceinanincreasinglysuburbanisedsociety,andsocialdiscrimination.Medicalresearchalsobecameinterestedintheimpactofstressonconditionssuchasheartdisease.Itis,again,aremarkableparadoxthattherapidlyincreasingwealthandsafetyinWesternsocietiesaftertheendofWorldWarIIshouldleadtoincreasingconcernsoverstress.Shouldn’tpeoplehavebeenblissfullyhappywiththeirnewpeacetimelives?Asitturnedout,theconstantflowofminor‘threats’inacompetitiveworkenvironment,suchasdeadlines,demandsforrapiddecisions,etc.,wereproducingasituationthatcontinuouslytriggersthenaturalstressresponseandtherebyproduceschronicstressinsteadoftherareemergencyresponsethatitevolvedfor.Itcouldalmostappearthatwar,withitsalternationofboredomandmomentsoflife-threateningcrisis,isbettersuitedtofitthenaturalstressresponse.However,inresponsetorecentchangesinthenatureofconflict,themilitaryhasalsobecomeinvolvedinstressresearch,withaviewtoreducetheimpactofcombatstressandtraumaintheirpersonnel.Theconceptofpost-traumaticstressdisorder(PTSD)wasalsopopularisedinthe1970s,particularlybyprotestorsagainsttheVietnamwar.Thisrecognisedpsychiatricconditionisseparatefromchronicstress.Typicalsymptomsincludefrequentintrusiveflashbacksinwhichthepatientinvoluntarilyre-experiencesthetraumaticeventstheyhavebeenexposedto,aswellasrecurringnightmares.Thesecanseverelyaffecttrust,confidence,concentration,sleep,andgeneralmood.Interestingly,PTSDismorelikelytobecausedbyman-madetrauma,suchasviolence,thanbynaturaldisasters,suchasforestfires.RedmindSincetheproblemsofchronicstressstartedtobecomeappreciatedinthe1970s,technologyhasmadehugeprogressandprovideduswithallkindsofdevicesdesignedtofacilitatetasks,thuspromisingtomakelifeeasierforus.Buthasitworkedout?Today,somebodyrunninglateforanappointmentnolongerhastolookforaphoneboothtomakeacall,andmotoristscanrelyontheirelectronichelperstofindthemostefficientrouteandavoidroadclosuresandtrafficjams.Andyetweappeartobenolessstressedthanwewereinthe1970s.Onthecontrary,psychologistsarewarningthatthepresenceofsmartphonesinourpockets,makinguscontactablearoundtheclockandwhereverwemaybe,mightaddtotheproblems.Whileeachindividualcontactmaybeeasilymanageable,thefactofbeingexposedtoexternaldemandsaroundtheclockisaddingtothechronicstress.Inthe‘always-on’society,itisbecomingincreasinglydifficulttoescapetheemailsandcallsfrombosses,colleaguesorcustomersdemandingimmediateattentionevenoutsideofficehours.Inabraveattempttoswimagainstthistide,Francehasrecentlylegislatedtomakeitillegaltoemailemployeesoutoftheirworkinghours.Anadditionalproblemcreatedbycommunicationstechnologyisthetemptationtousemanychannelsatthesametime.Whilemanypeopleliketobelievetheycaneasilymanagemultitasking,psychologistsandneuroscientistshavewarnedthatwhatSpecialIssueR407,nnicBluesolutions:Theserenitywegetfromlookingoutacrosstheseaorlargeriverscanhelptorestorehormonalbalanceandovercomestress-relatedproblems,asWallaceJ.Nicholsarguesinhisnewbook,BlueMind.TheimageshowstheskylineofFrankfurt,Germany,exudingcalmafterabusydayforbankersandbuilders.(Photo:MichaelGross.)theyactuallydoisswitchingbackandforthbetweenseparateactivitieswhichmaymeanthatoneofthemisn’tgettingenoughattention.Thisiswhymanycountrieshavehadtobantheuseofmobilephoneswhiledriving.Thechronicstressheightenedbyrelentlessintrusionofcommunicationgadgetsintoallaspectsofourlivespresentssignificanthealthproblemsithelongterm,saysCatherineFranssefromJamesMadisonUniversityatHarrisonburg,Virginia,US.“Mostoftheleadingcausesofdebilitatingillnessanddeatharecorrelatedwith,ifnotcausedby,stress,”Franssenexplains.“Loadsofresearchhasprovideddirectlinksbetweenstressandheartdisease,stroke,diabetes,andsuicide/self-harm.Further,stresscanimpacttheimmunesystem,leadingtovulnerabilitytoinfectiousandchrondiseases.Andweneedonlytolookatourownlivestonotethatmoreaccidentshappenwhenwearestressed.Whilesomeofthoseaccidentsareassimpleasslicingafingerinsteadofavegetablewhilepreparingamealtooquickly,alltoomanyaccidentsaremuchmoresevere—particularlywhenyouaddintherisksofmultitasking.”Asaremedyforchronicstress,sheadvocatesgivingthestressresponsesystem,whichshelikestocallthe“redmind”(incontrasttothemorerelaxed“bluemind”whichwewillencounterbelow),somerealworktodo.Fromherownexperienceasaskydiver,Franssenknowsthatactivitiesconfrontingtheredmindwithrealdangerinthewayitevolvedtooperatecanputthesignificanceofeverydaystressorsintoperspective.“Istartedskydivingingraduateschoolandbecamequicklyhookednoonlyontheadrenalinerush,butalsothsuper-fastproblem-solvingchallengesthatsportprovided,”Franssenrecalls.“WhenIreturnedtothetrialsoftop-tiegraduatestudyafteraweekendofskydiving,Ifoundmyselfcalmer,morerelaxed,andbetterabletoputthestrainofdeadlinesandexperimentaldifficultiesintoperspective.That,atleast,wasn’tlifeordeath!”Recently,Franssenhasstudiedthehormoneresponsesofextremeclimbersandfoundthattheirlevelsofstresshormoneswerelowerthanthoseofcontrolsubjectsintercomparablesituations,suchastakingcollegeexams.Sheiscontinuingthisworkwithotherextremesportsenthusiaststoexplorewhetherextremesportsmightreallybeascientificallyviablealternativetreatmentforanxiety.Communicationsmediaapart,anotherimportantareathatcansignificantlyrelieveoraddtochronicstressisurbanplanningandtransport.AsCharlesMontgomeryhasexplainedinhisrecentbookHappyCity,thedevelopmentofcar-friendlycities,suchasLosAngelesandAtlantaintheUSorMiltonKeynesintheUK,duringthesecondhalfofthe20thcenturyhasaddedtocommuterstressandseducedpeopleintounhealthyhabitsofwalkinglessanddrivingeverywhere.Montgomerycitesresearchshowingthatpeoplewouldonaverageliketospend16minutesgettingtotheirworkplace,andtendtobehappierwhentheycanwalkorcycletowork.IntheUS,however,90%ofcommutersdrive,andtheirjourneytakesmorethan25minuteseachwayonaverage.Experimentshaveshownthatunhappycommutersstuckintheircarshaveunhealthy,chronicallyelevatedlevelsofstresshormonesintheircirculation.Inextremis,roadrageincidentsorrecklessdrivingcanbetheresultofthishormonaloverload.Reversingdecadesofplanningthathasmadepeoplemorestressedandlesshappywillrequireinterventionsbackedbyastrongpoliticalwill.MontgomerycitesthecityofBogotá,Colombia,asapositiveexample.Backinthe1990s,motortraffictherewasnotoriouslydangerous,andalternativesnonexistent.Theintroductionofcar-reductionschemesandanewpublictransportsystemintheearly2000s,alongwiththeimprovingpoliticalsecuritysituation,hasachievedadramaticturn-around,makingthecitysafeandenjoyableforallroadusersincludingcyclistsandpedestrians.BluemindIfyou’resufferingfromchronicstressanddon’thavethepowertoredesignyourcitynorthecouragetotakeupskydiving,whatcanyoudoaboutit?WallaceJ.Nichols,aResearchAssociateattheCaliforniaAcademyofSciencesatSanFrancisco,California,recommendstogowhereveryoucanfindwater.Nicholsisanecologistwhoworksonconservationofseaturtles,whichledhimtobecomeinterestedintheinfluenceoftheoceansonouremotionalwell-being(Curr.Biol.(2013)23,R501–R504).Nicholscoinedthephrase“bluemind”forthisinterfacebetweenCurrentBiologyVol24No10R408Mobilemadness:Electronicgadgetslikesmartphonesandtheassociatedcultureofalwaysbeingonlinehaveaddedtothestressofmodernlife.Psychologistswarnthatmultitaskingcandiminishtheattentionwecandevotetoanimportanttask,whichcanbeparticularlydangerouswhendriving.(Photo:ChristopherJ.Mills.)ourpsychologyandournaturalenvironment.HeorganisestheBlueMindconferenceseries,thefourthinstalmentofwhichtakesplaceatBedruthanSteps,Cornwall,UK,10–12June2014,andwillbelive-streamedontheweb(www.bluemind.me).AsNicholsdescribesit:“overthepastseveralyearsI’vebroughttogetheraneclecticgroupofscientists,psychologists,researchers,educators,athletes,explorers,businesspeople,andartiststoconsiderafundamentalquestion:whathappenswhenourmostcomplexorgan—thebrain—meetstheplanet’slargestfeature—water?”Hehasalsoexplainedtheseideasinanewbook,calledBlueMind:HowWaterMakesYouHappier,MoreConnected,andBetteratWhatYouDo,whichisalsoduetoappearinJune.Inhisbook,Nicholsdiscussesaspateofrecentpsychologypapersshowingthattheproximityof“bluenature”canimprovepeople’sphysicalandmentalhealthandcounterbalancethedamagingeffectsofthechronicstressandthepermanentengagementoftheredmind.Whiletheopportunitytoexerciseplaysapart,severalstudieshaveshownthatthepositiveeffectofbeingnearwatercanbeseparatedfromthataspect.Waterhasalsoprovenbeneficialforpeoplewithspecificproblemsbeyondchronicstress.NicholscitesasexamplesorganisationsthatofferkayakingexcursionsforwarveteranswithPTSDand/orphysicalinjuries,suchasRiversofRecovery(ROR).Childrenwithautismarealsowidelyreportedtohaveanaturalaffinityforwaterandtobenefitfromthecalmingeffectofbeingnearoronthewater.“PractisingBlueMindisnosilverbulletsolution,”Nicholsconcludes,“butwhenunderstoodandusedinconjunctionwithindoorrelaxationpracticeswefindittobewidelyuseful.Bydescribingandassigningthefullvalueofthecognitiveandemotionalbenefitsandservicestohealthywaterwaysandoceansweprovideacompellingadditionalargumentforrestoration,protection,maintenanceandaccess.”Whetheryoudecidetoreducestressbywalkingtowork,bydoingyogaonthebeach,orbyjumpingoutofplanes,itallboilsdowntofindingthenaturalbalancebetweenthehighlyalertredmindandtherelaxedbluemind.MichaelGrossisasciencewriterbasedatOxford.Hecanbecontactedviahiswebpageatwww.michaelgross.co.ukPrimerStressandlifehistoryPatMonaghanandKarenA.SpencerInhisbookonbehaviouralendocrinology,RandyNelsondescribes‘stress’asa‘notoriouslyetherealconcept’.Yet,despitethislackofclarity,studiesoftheconsequencesofstressacrossdifferenttimescales,lifehistorystages,taxaandlevelsofbiologicalenquiryformalargepartofmodernbiologyandbiomedicine.Organismsneedtorecogniseandrespondtoenvironmentalchallenges.Beingabletodosoappropriately,andwithminimalcosts,isanimportantphysiologicalattribute,withgreatadaptivevalue.Thecostsandbenefitsofdifferentmechanismsthatenableorganismstocopewithunpredictableenvironmentalchangescanbemanifesttodifferentdegreesatdifferentlifestages.Accordingly,thelevelofstressexperiencedintheenvironmentcanactasastrongselectivepressurethatdrivestheevolutionoflifehistories.Thoughtightdefinitionshavecertainlyprovedproblematic,thereisconsiderableconsensusaboutwhatstressisandwhyitplayssuchanimportantpartinshapinglifehistories.Themorechallengingtheenvironment,themoreimportantisthestressresponsesystem.Theconceptofstressiscloselyrelatedtotheconceptofhomeostasis.Botharebestviewedasbiologicalstates,thelatterrepresentingtheoptimalphysiologicalstateor‘comfortzone’,andtheformerthestatethatariseswhenhomeostasisisdisrupted.Wecanthinkoforganismsasoccupyingamulti-dimensionalphysiologicalspace,inwhichtheyhaveoptimalzonesorsetpointsforkeybodyparameters,suchastemperature,metabolicactivity,energybalance,bloodflow,waterbalanceandsoon.Wheninternalorexternalcircumstancesgiverisetoasituationthattakes,orthreatenstotake,theindividualoutofitszoneoftoleranceforoneoranumberofparameters,orcauseitdirectharm,