The Future of Aging: Pathways to Human Life Extension

872 Pages·2010·15.58 MB·English

by  Ray Kurzweil

The Future of Aging

· ·
Gregory M. Fahy Michael D. West
·
L. Stephen Coles Steven B. Harris
Editors
The Future of Aging
Pathways to Human Life Extension
123
Editors
GregoryM.Fahy Dr.MichaelD.West
InterveneBiomedical,LLC BioTime,Inc.
Box478 1301HarborBayParkway
NorcoCA92860 AlamedaCA94502
USA USA
[email protected] [email protected]
L.StephenColes StevenB.Harris
InstituteofMolecularBiology CriticalCareResearch,Inc.
DepartmentofChemistryandBiochemistry 10743CivicCenterDrive
YoungHall RanchoCucamongaCA
UniversityofCalifornia 91730
LosAngeles USA
CA90095-1569 [email protected]
USA
[email protected]
ISBN978-90-481-3998-9 e-ISBN978-90-481-3999-6
DOI10.1007/978-90-481-3999-6
SpringerDordrechtHeidelbergLondonNewYork
LibraryofCongressControlNumber:2010927444
©SpringerScience+BusinessMediaB.V.2010
Nopartofthisworkmaybereproduced,storedinaretrievalsystem,ortransmittedinanyformorby
anymeans,electronic,mechanical,photocopying,microfilming,recordingorotherwise,withoutwritten
permissionfromthePublisher,withtheexceptionofanymaterialsuppliedspecificallyforthepurpose
ofbeingenteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthework.
Coverillustration:Onthecover:Thesmallnematodeworm,C.elegans(wavylines),canrealizesome
verylargegainsinlifespan.ComparedtothestandardN2DRM(wild-type)worm,wormswithastrong
mutationinasinglegene(theage-1(mg44)allele)canlive10timeslonger,andcandosoinexcellent
health.Thisstrikingresultbringsintoquestiontheverynatureofaging,andraisesthepossibilityof
somedayextendingthelifespansofhumansingoodhealthaswell.Thelattersubjectisthethemetaken
upinthisbook.
Printedonacid-freepaper
SpringerispartofSpringerScience+BusinessMedia(www.springer.com)
Thisbookisdedicatedtothefondmemoryof
ChristopherB.Heward,Ph.D.,atirelessand
dedicatedclinicalbiogerontologistandasuperb
laboratoryscientistwhoworkedattheinterface
ofbusinessandbiomedicineasthePresidentof
theKronosScienceLaboratories,wherehe
conceivedandpursuedavarietyofresearchand
developmentprojectsaimedvariouslyatearly
detectionandpreventionofage-relateddiseases
andunderstandingandslowingtheaging
processinpatients.Hewasinternationally
recognizedasaseminalthinkerintheareaof
biologicalagingandwastheauthorand
co-authorofnumerousscientificarticlesand
bookchapters.Hewasaconsummatelyskeptical
enthusiastforinterventivegerontology.
ItisanextremeandtragicironythatChris
developedcanceratarelativelyyoungageand
diedonJanuary10,2009afteravigorous
3-monthbattle. Hesetamagnificentexampleof
howtolivelifecourageouslytothefullest
withoutillusion. Hewillbesorelymissedbyall
whoknewhim.

Preface
Biogerontologyiscomingofage.Itnowseemsclearthatafundamentalunderstand-
ingofthemolecularpathwaysunderlyingage-relatedpathologyhasthepotentialto
translateintoaneteconomicimpactofoveratrilliondollarsayearintheUSalone
and to alleviate a massive toll of human suffering. At the same time, a tidal wave
ofagingpostWorldWarIIbabyboomersispoisedtobeginfloodingtheshoresof
ourhealthcaresystemwithinthecomingdecade.Itisthereforenowstrategicand
timelyformedicalresearchtoturnitsattentiontothemolecularandcellularmech-
anismsofagingandage-relateddisease,andthepurposeofthisbookistoprovide
a broad perspective on future possibilities for mitigating aging and improving the
human condition that can be envisioned today based on available knowledge and
reasonablededuction.
Oneofthelargestbarrierstosuccessfulinterventioninagingislikelypsycholog-
icalratherthantechnological.Awidespreadmisperceptionpersiststhatmodifying
humanagingbordersontheimpossible.However,thisskepticismisnotsupported
by science. There are now numerous examples of therapies based on fundamental
insights in molecular biogerontology that are in clinical development, and many
moresuchtherapiesareexpectedtounfoldovertimescalesrangingfromthevery
near term to the more distant future. We call attention to many of these in this
volume.
Without a doubt, there has never been a more exciting time in the history of
biogerontology than the present and, just as certainly, the best is yet to come. Ten
yearsago,LeonardGuarenteandCynthiaKenyonexpressedtheirgrowingsenseof
hope and optimism about the future of biogerontology in these inspiring words in
anoutstandingarticleinNature(GuarenteandKenyon2000):
Thefieldofageingresearchhasbeencompletelytransformedinthepastdecade....When
singlegenesarechanged,animalsthatshouldbeoldstayyoung.Inhumans,thesemutants
wouldbeanalogoustoaninetyyearoldwholooksandfeelsforty-five.Onthisbasiswe
begintothinkofageingasadiseasethatcanbecured,oratleastpostponed....Thefield
ofageingisbeginningtoexplode,becausesomanyaresoexcitedabouttheprospectof
searchingfor–andfinding–thecausesofageing,andmaybeeventhefountainofyouth
itself.
Buttheresultsthatstimulatedsuchhopein2000havebeenfarsurpassedinthe
last ten years. To give just one example, the seminal observation in the 1980s that
vii
viii Preface
geneticdamage(theage-1mutation)inC.eleganscouldextendlifespanby40–65%
(Klass1983;Johnson1987;FriedmanandJohnson1988),whichultimatelyledto
themodernparadigmofgeneticregulationofaging,wasconfirmedbutonapracti-
calleveldwarfedin2007bythediscoverythatstrongermutationsinthesameage-1
genecanactuallyextendlifespaninC.elegansbyastaggering10-fold(Ayyadevara
etal.2008;ShmooklerReisandMcEwen2010).Thefindingthatagenetichierarchy
controlledbyonegenecanineffectcontrol100%ofthenormalagingprocessfora
timeinexcessofthenormalmaximumlifespaninatleastthisspeciesisaprofound
development that we celebrate on the cover of the present volume as symbolic of
thefuturepotentialofinterventivegerontology.Norhaveresultswithhigherorgan-
isms failed to excite the interest of biogerontologists, the public, and the business
communityaswell.Therecentlargeinvestmentinbiogerontologybyamajorphar-
maceuticalcompanymarksaneweraofpromiseforinterventionintohumanaging.
Despitealloftheprogressofthepastdecadeofbiogerontologicalresearch,una-
nimity of views on the meaning and implications of present knowledge has not
yetbeenachieved.Differentinterpretationsofandhypothesesaboutagingarestill
possible, and controversy continues even over the meaning of specific animal and
cellularmodelsandtheireventualapplicabilityorlackofapplicabilitytoorimplica-
tions for human intervention. Accordingly, the reader willnotice basic differences
of opinion between some of the contributors to this book. This is as it should be,
and it is hoped that some of these disagreements will be stimulating. In fact, we
maybejustifiablyaccusedofdeliberatelystokingthefiresofdisagreementinsome
casesintheinterestsofpromotingdebateandtherebyacceleratingtheresolutionof
conflictingviewsandstimulatingnewthoughtsingeneral.
Despite some present disagreements, however, the more important truth is that
modernbiogerontologyhasdevelopedmanycommonly-agreeduponbroadthemes
thatseemsufficientlyreliabletojustifyanexaminationoftheirimplicationsforthe
futureofhumanaging,andsuchanexaminationnowseemsparticularlytimely.
Although this book is entitled “The Future of Aging,” no one can predict the
futureinspecificdetail,andwedonotattempttodothishere.Instead,ourgoalis
onlytoprovideabroaderandmorecompleteandpracticalsenseofwhatthefuture
mightbringthanhasbeenavailableinoneplaceheretofore.
PartOneofthisvolumeconsidershistorical,anthropological,philosophical,eth-
ical,evolutionary,andgeneralevidentiaryperspectivesontheproposalthatagingin
thefuturemaybeappreciablydifferentfromagingasitisexperiencedtoday.Given
often-repeatedskepticismthatagingeithercanorshouldbesignificantlymodified
in man, the arguments in Part One should help to establish the contrary view that
aginginterventionoughttobebothgenerallyfeasibleanddesirable.
Part Two presents many specific and potentially transformative proposed inter-
ventive approaches, organized in roughly chronological order, with the earliest
interventionscomingfirstandthemoredistantinterventionscominglast.Onecan
imagine useful interventions proceeding in a series of steps, many of which seem
likelytobestepsoutlinedinthisbook.Thepossiblestepsdescribedherebeginto
provide a kind of tentative roadmap to the future of potential pathways to human
life extension in which greater and greater control over aging is achieved over the
Preface ix
nextseveraldecades.Butitseemsunlikelywewillhavetowaitdecadesformajor
changestobecomeevident.Infact,intryingtodecideonthesequenceofchapters
in Part Two, it was striking how many of these chapters, while offering powerful
andparadigm-changingpotentialinterventions,arealsovyingtobeamongthefirst
to have their approach put into practice. And yet even as impressive as the cur-
rent list of interventive approaches is, the rapid pace of ongoing developments in
biogerontologyensuresthatthelistisincomplete,afactthatunderscoresevenmore
thepotentialthatliesahead.
Itishopedthatthepresentglimpseintothefutureofhumanagingandtherefine-
ments to it that will follow will be of assistance to policy makers as they attempt
to decide how public funds should be directed and how population aging should
beaddressed.Governmentalprojectionsoffuturehumanlifeexpectancyhavebeen
consistentlyandsignificantlyinerrorinfailingtoanticipatesteadyandevenaccel-
eratingreductionsinmortalityrates(Horiuchi2000;Tuljapurkaretal.2000;Vaupel
2010), perhaps in part because of the lack of an adequately convincing argument
for or any sufficiently concrete therapeutic basis for a timetable for greater future
longevity. In addition, current NIH spending priorities continue to ignore the fact
thatlearninghowtosuccessfullymitigateagingitselfwouldbeadramaticallymore
efficientandthereforemorehumanewaytodealwiththediseasesofaging,which
accountforthebulkofUShealthcareexpenditures,thancontinuingtodevotesuch
an overwhelming share of our research resources to a piecemeal attack on these
diseases.Althoughthispointhasbeenmademanytimesbefore,perhapstheavail-
ability of a credible roadmap to a better future for aging will make the argument
easierforpolicymakerstoacceptinthefuture.
In the end, the extent to which aging can be modified will impact all of us
and our loved ones in a very personal way. This bald fact alone justifies bring-
ing together thought leaders in the field of aging research to attempt to glimpse
the future even if we are at a time in history when the full function of the human
genomeisnotknownandourpresentknowledgeofagingremainsveryincomplete.
Fortunately, despite the acknowledged limitations of today’s knowledge, today’s
evidence already speaks for itself. We truly and unquestionably are learning how
tointervene,indiverseways,intoaging,anditseemsinevitablethatthiswillmate-
riallyaffecthumanaging.Thefutureofagingwillbegintoarrivesoonerthanmany
ofusthink.
WethanktheeditorialstaffatSpringer,andparticularlyFabiodeCastro,Marlies
Vlot,andTanjavanGaans,fortheirtrustandfortheirsteadfastsupportofourcon-
ceptforthisbook,eveninthefaceofsomestrongoppositionbycertainreviewers.
Wethankaswellalloftheanonymousreviewersoftheconceptofthisbook,whose
commentsbothproandconhelpedustorefineourmessage.WealsothankBrenda
Peters for her devoted, highly skillful, cheerful, and very helpful volunteer edito-
rialassistance,andKarenJessieofIntegraIndiaforoutstandingandunderstanding
productionassistance.
Finally, we thank our many wonderful authors, who cheerfully and patiently
endured an at times rather vigorous process of peer review. Their opinions, of
course,remaintheirown!