FOCUS_Aging

A Hint of Immortality

Eternal life lasts a very long time. Nevertheless, Ralf Schaible from the Max Planck Institute for Demographic Research in Rostock can already affirm that the freshwater polyp Hydra comes quite close to this ideal. In a long-term experiment initiated by the institute’s Director James W. Vaupel, he and his colleagues investigate why, under certain circumstances, Hydra doesn’t age.

TEXT KLAUS WILHELM

he freshwater polyps at the says Schaible, summing up the experi- ening. Others confidently proclaim Max Planck Institute in Ros- ment’s spectacular findings, “it’s had a that they don’t care – even though per- tock get absolutely every- constant mortality rate throughout all haps they, too, stand in front of the thing they need for a long these years.” Previously that seemed, mirror each morning and furtively but life. After all, “the experi- from a scientific perspective, impossible. meticulously examine their wrinkles. T ment,” as Ralf Schaible calls it, has no And who knows: maybe they also se- use for unhappy animals. That’s why THE BODY BREAKS DOWN cretly hope that science will one day be Schaible creates paradisiacal conditions WITH AGE able to halt this course of events, like for these tiny animals, which measure the medieval alchemists who sought less than one centimeter in length and Aging, mortality, immortality – these the elixir of eternal life. In Ralf are as thin as a needle: “We pamper topics have held a fascination for hu- Schaible’s view, however, that was – them with everything they could ever mans since well before the post-post- and is – a vain hope: “I think immor- dream of.” Several of his staff are tasked post-modern era. And for good reason: tality is impossible,” he says, “even in with feeding the nearly 1,800 polyps. dark circles plow ever deeper furrows an organism like Hydra.” Using extremely fine pipettes, they de- under our eyes. Our skin and connec- Hydra possesses truly astonishing posit the polyps’ favorite food directly tive tissues sag. Wrinkles cover our properties – just like the eponymous onto their tentacles: brine shrimps, necks and faces. Reading glasses sit on character in Greek mythology, the small crustaceans. They get the same ra- our noses like a senior citizen ID card. many-headed monster that grew two tion every time, delivered free of Our minds aren’t as quick as they once new heads for each one it lost. And the charge, three times a week – and that were. The sprint to the next bus stop head in the middle of its body is im- for nearly ten years now. becomes more like a tired trot. mortal, besides. The Hydra seems to enjoy it. Under No, aging is no fun, and with every Like its mythological role model, these conditions, the species has now re- passing day, the risk of dying increas- the freshwater polyp, too, replaces the

vealed its secret: “Hydra doesn’t age,” es. Some of us find the process fright- body parts it loses. “But why can they Photo: Fotostudio Hagedorn

28 MaxPlanckResearch 3 | 15 Delicate beauty: Hydra, which grows to a size of just one centimeter, is tougher than its frail-looking body suggests. In the lab, this freshwater polyp can theoretically reach an age of several hundred years. do that and others can’t?” Schaible spoil Hydra 1 from cohort number 1, as live in their petri dishes without fish wonders. Does it have to do with Hydra’s well as all the offspring it produced. or other animals that might eat them. extreme longevity? Each animal lives in its own dish Right after the start of the experi- The longer the experiment contin- of water with minerals at a constant ment, Hydra 1 began to reproduce ues, the more convinced the researcher temperature of 18 degrees Celsius. asexually. The researchers collected the becomes that it does. With an expect- They always receive the same amount offspring and gave each of them a “pri- ed end date on December 31, 2017, the of food and follow the rhythm of a vate room” as well – more than 1,800 experiment began on March 1, 2006. normal day with light and darkness. times to date. That’s when the scientists began to To round out this life of luxury, they Nevertheless, there are some deaths. Most of them are due to lab acci- dents, for instance when individuals stick to the covers of their dishes and LONG-LIVED CLAMS dry out, or fall on the floor. But the occasional Hydra also dies a natural The ocean quahog Arctica islandica is the longest-lived complex animal on Earth. death: it first stops eating and short- One specimen of this shellfish verifiably made it to the ripe old age of over 500 ens its tentacles; next, the entire body years old – as evidenced by the lines on its shell. Populations of Arctica islandica begins to shrink; after one to two also live, for example, in the Baltic Sea. There, however, they die between the weeks, the animal dissolves into its ages of 40 and 60. A comparison of Icelandic, Irish and Baltic clams shows that component parts. “But so far,” says all clam populations have the same aging pattern despite differences in their Schaible, “we have rarely observed maximum lifespans. Thus, their mortality increases only slightly with increas- this kind of death.” ing age. This doesn’t appear to have anything to do with the telomeres, as there The scientists also determine the is no difference in these protective caps on the ends of the chromosomes. asexual reproduction rate. For this, According to popular theories, the telomeres are considered to be the “bomb they count every new daughter organ- fuse of death,” since they get a tiny bit shorter each time a cell divides, thus lim- ism. “To date, more than 30,000 genet- iting the life of the cells, much like an hourglass. ically identical polyps have been cre- ated in this way,” says Schaible. He has

detailed data from more than 1,800 in- Photo: Fotostudio Hagedorn

30 MaxPlanckResearch 3 | 15 Graphic: Ralf Schaible, MPI for Demographic Research and molecules:musclestrength and ical standpoint,andatthelevel ofcells tend tolookatagingfroma physiolog- researcher. Naturalscientistsnormally to understand,”saystheRostock-based world, andonethatIfirsthad tolearn Schaible, thisisan“entirelydifferent death inanimals.Forbiologistslike been analyzingtheprobabilitiesof raphy have,forsometimenow, also Biodemog- ofEvolutionary Laboratory tists workingwithJamesVaupel inthe raphers callaging. probability ofdeathiswhatdemog- usually increasing.Thechangeinthe bility ofdeathchangescontinually, in thisfactor. Inhumans,theproba- raphers havealwaysbeeninterested ability ofdeathforeachage.Demog- nual deaths,theycalculatetheprob- many years.Fromthenumberofan- the animals’naturalmortalityover long-term experimentistodetermine ers just10or20. has produced341offspringsofar, oth- dividuals. Themostproductiveanimal genetically identical,orclones. exception ofmostlyinsignificantmutations, tion, motheranddaughterare, withthe tentacles. Inthistypeofvegetative reproduc- a completeanimal,includingfoot and ofbud,whichdevelops into the bodytoasort asexually: stemcellsmigrate from thecore of mixed anew. More frequently, Hydraprocreates material ofthetwoindividualsinvolved is there. Inthisform ofreproduction, thegenetic the ground anddevelops intoanadult animal detaches from themotherorganism, fallsto theirova. individuals andfertilize The embryo into thewater. They are pickedupbyfemale individual produces spermandsecretes them asexually. For sexualreproduction, an Right: small crustaceansintothedishes. day.every They usefinepipettestodispense have toprovide food tonearly Left: Dailyfeeding routine: The researchers It isinthiscontextthatthescien- The researchers’ aim for their Hydra canreproduce bothsexuallyand 1,800 polyps viduals dies.Alltheotherscontinue on Per year, onlyoneinaround220indi- low, especiallyfor suchasmallanimal. Moreover, the mortalityissurprisingly stant mortalityrisk,anditdoesn’t age Now theyknowthat“Hydrahasacon- the polypsarebornandwhentheydie. records fornineyearsnowaboutwhen tock hasthusbeenkeepingmeticulous differentways.TheteaminRos- very show thatorganismsageanddiein Hydra experimentofferedthechanceto and soon. of alife,thegeneticmake-upchanges, metabolic ratesdecreaseoverthespan page 26)–soit’s notimmortal,butal- life expectancyofseveralcenturies (see and onon.Thepolyp thus hasa PER YEAR HARDLY ANYFATALITIES nine, itsriskofdyingremainsthesame. er anindividualisjustoneyearoldor with increasinglifespan.” because itsmortalitydoesn’t change In otherwords,regardlessofwheth- Schaible realized,however, thatthe Asexual cycle Male Sperm

Female the standard curve andresemblesthat the standardcurve zees, theprobabilityofdeath follows patterns innature. page 26)showsthediversity ofaging in Odense,Denmark,calculated (see Center ontheBiodemographyofAging Rostock andtheMax-PlanckOdense leagues attheMaxPlanckInstitutein species thatJamesVaupel andhiscol- ity ofdeathandthereproduction46 ty decreases.Thedataontheprobabil- turity, mortalityincreaseswhilefertili- that,uponreachingsexualma- theory – afindingthatcontradictsthepopular by environmentalconditions. able andareinfluencedbygenes that agingprocessesareextremelyvari- clusive. Itsupportedthehypothesis abated –thedatawassimplytoocon- simplistic. Butthecriticismgradually scientist. Theexperimentwassaidtobe ridiculed ourfindings,”concedesthe must beaneternity,” saysSchaible. small, fragileorganism,eventenyears most. “Onemightthinkthatforsucha Eggs In primates,baboonsandchimpan- So livingorganismsagedifferently “The scientificcommunityinitially Sexual cycle 3 | MaxPlanckResearch 15MaxPlanckResearch FOCUS_Aging 31 FOCUS_Aging oligactis. Atawatertemperatureof18 for instance,studiedthespeciesHydra explains Schaible.Japanesebiologists, within aspeciesorgroupofanimals,” 32 is incorrect. years andinevitablyleadto itsdeath late inanorganism’s cellsoverthe mutations andotherdamage accumu- parently, however, theold notionthat temperatures oratrueaging effect.Ap- tality ismerelyanadaptationtolower know whetherthedifferenceinmor- Hydra ingeneral. tion doesn’t reducelifeexpectancyin doesn’t increase.Sosexualreproduc- er, inthesame experiment,mortality mans. InotherHydraspecies,howev- increases withtime–justasinhu- In thiscase,theprobabilityofdeath and sperm,dieafterfivemonths. the animalsnowproduceonlyeggs reproduce sexually. Thismeansthat grees, incontrast,thespeciesbeginsto duce budsanddon’t age. At14de- degrees, theanimalsdiligentlypro- ever, isuniqueintheanimalkingdom. tremely lowmortalityofHydra,how- mains constant.Theconstantandex- death initiallyincreasesandthenre- successfully. Inmanybirds,theriskof thus withstandpredatorsevermore cause theygroweverlargerandcan even wellintooldage–probablybe- mortality riskdecreasescontinually or theCaliforniandeserttortoise– the violescentsea-whipcoral,oak of humans.Inotherspecies–suchas (right). zone bud inthe grow tentacles many treated the of insome (left), animals Hydra after Two weeks 1 mm MaxPlanckResearch 3 MaxPlanckResearch “But the aging processes also vary “But theagingprocessesalsovary The researchers thereforedon’t yet was treated with UV light, the polyps changed visibly: In contrast to untreated untreated to Incontrast visibly: changed polyps the light, UV with treated was | 15 Hydra , two heads form, and the buds don’t detach (center). In others, Inothers, (center). detach don’t buds the and form, heads , two

into twohalves,intothreedays, this decline.Ifafreshwaterpolypiscut tions inthelab,Hydraisabletoescape pacity, andundertheluxuriouscondi- Thanks toitsimmenseregenerativeca- ever olderwithoutdecaying. spite continuousreproduction,togrow ly renewingitself,allowingHydra,de- al bodyparts.Itsisthusconstant- form orregenerateabodyindividu- and produceallcelltypesneededto stem cellsdividethroughouttheirlives than specializedsomaticcells.These stem cells,whichHydrahasmoreof It owesthisabilitytorenewitself YOUTH SELF-RENEWAL PRESERVES still regeneratequicklyandprecisely. pieces andonly500cellsremain,itcan grow. Eveniftheanimaliscutintofive two completenewindividualswill spring ensures the survival ofthegenet- spring ensuresthesurvival production ofgeneticallyidentical off- in nature.Forexample,the constant aptations thathelptheanimals survive may alsobemerelyaby-product ofad- its fountainofyouth,”saysSchaible. asexual reproductionissimultaneously no priceforitsextendedlifespan– conditions. “OurHydraapparentlypays wiped outbyadverseenvironmental genes ofanindividualorganismwillbe viduals reducetheprobabilitythat spring. Manygeneticallyidenticalindi- ously producesgeneticallyidenticaloff-

This quasiimmortalityin the lab Through budding,Hydracontinu-

2 mm due toenvironmentalfactors.More- ic materialevenwhenmortalityishigh somatic cells,eventuallydie. cialize and,duetotheshort lifespan of the footandtentacles,where theyspe- few cellsaredamaged,they are sentto different ways,”explainsSchaible. If cells. Itthenrespondstothe damagein guish intactstemcellsfromdamaged regenerate anew. pens withthedamagewhenpolyps searchers wantedtoknowwhathap- their previousappearance.Nowthere- most ofthemrecoveredandregained ing multipleheadsorslittentacles,but exposure. Someweredeformed,grow- 30 percent diedimmediatelyfollowing considerable stressfortheanimals,and sive hydrogenperoxide.Bothcaused UV lightortreatedthemwithaggres- tists irradiatedthepolypswithharmful further extendedtheirlifespans. used itmorewisely, whichmayhave They thusgainedmorelifeenergyand polyps reproducingmoreefficiently. brine shrimpsagain.Thisresultedinthe them fastfor60days,thengiving first feedingthemnormally, thenletting subjected thepolypstominorstress, out whytheirpolypsdon’t age.They launched afewshorterstudiestofind periment, theresearchers inRostock such assnails,nibbleonthem. vival rate,forinstancewhenpredators, polyps toregenerateincreasestheirsur- over, abilityofthe theextraordinary “Hydra seemstobeabledistin- In anotherexperiment,thescien- In parallelwiththelong-termex-

Photos: Ralf Schaible, MPI for Demographic Research Photo: Fotostudio Hagedorn esmtigseil” be somethingspecial.” a non-agingorganism,itwould really were tofindthegenesforaging insuch is afascinatingcaseoflongevity. “Ifwe extremely long-lived,non-aging polyp the animals’mortalityrate. of FOXOandothergenes,increasing of scientists canmodifytheagingprocess puts it.Usingspecialsubstances,the renewal andlongevity,” asSchaible genes –“asortofmasterswitchforcell that regulatestheactivityofmany name ofaso-calledtranscriptionfactor marily ontheproteinFOXO.That’s the their animals.Theyarefocusingpri- molecules arebehindthelongevityof ther experimentstodeterminewhich They themselvesperish. which healthyoffspringthengrow. few intactcellsintothebuds,from pears tobeaselflessact:theymovethe Others sacrificethemselvesinwhatap- possibly livelonger,” saysSchaible. yps getridofthedamagedcellsand new collect theminthebuds,fromwhich and deportthedamagedcells.They strategies: somebehaveegotistically might chooseoneoftwodifferent cells floodtheorganism,animals However, iftoomanymaltreatedstem the polyp’s genes. also lookingfor theanswer tothisquestion in thesecretWhat’s oflongevity?RalfSchaibleis Hydra andprobablyalsotheactivity For Schaibleandhiscolleagues, the The scientistswanttoconductfur- Hydra form.“Inthisway, thepol-

● ● TO THEPOINT Hydra: GLOSSARY ous cnidocyteswhentouched. it usestocapture prey. The tentaclesare equipped withcnidoblasts,whichshootoutpoison- a foot withwhichitanchorsitselftotheground, andaheadwithfive toeighttentaclesthat lakes andinriver sectionswhere flow toorapidly. thewaterdoesn’t The animalconsistsof of around twenty Hydraspecies,five ofwhichare found inGermany. They live inpondsand

over time. somatic cellswithnewones.Thisallowsittooffloadthecelldamage thatincreases Stem cellsthatareactivethroughouttheirlifespangiveHydratheabilitytoreplaceold its life–unlikewithhumans,whosemortalityriskincreases age. For thefreshwaterpolypHydra,probabilityofdyingremainsconstantthroughout The genusHydrabelongstotheCnidaria , whichalsoincludesjellyfish.Biologists know 3 | MaxPlanckResearch 15MaxPlanckResearch 33