A real cure for aging is no longer science fiction

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A real cure for aging is no longer science
fiction Aubrey D.N.J. de Grey Department of
Genetics, University of Cambridge Email
ag24_at_gen.cam.ac.uk Reprints, general info
http//www.gen.cam.ac.uk/sens/
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Something you may not know Your parents almost
certainly want you to die unnecessarily young
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Something you may not know Almost all adults
want everyone to die of aging, by age 120 or so,
forever
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Why? Fun Not fun
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The global trance Some common excuses for not
curing aging Wouldnt it be crushingly
boring? How would we pay the pensions? What
about starving Africans? Dictators would rule
forever! Claim nobody is that blind about
anything else -- so, they MUST be in a trance
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Q Why is aging defended? A Because it is
agreed to be awful, but its inevitable Except
one day, it wont be Topic of todays talk that
day is soon -- we can already hasten it
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FAQ 1 What is the big new idea?
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Aging in a nutshell Metabolism (the hugely messy
network of homeostatic processes that keep us
alive) causes Pathology (the hugely messy network
of anti-homeostatic processes that kill us) This
is not controversial -- indeed, it is why most
biogerontologists think theres little hope of
curing aging for ages
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A very simple observation Aging is indisputably
a side-effect of essential biochemical and
cellular processes BUT Its functional effect
(loss of performance) is delayed Putting it
another way Being alive must have immediate
side-effects, since metabolically active
molecules are short-lived BUT Those effects must
accumulate, and have a threshold level below
which they are harmless
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Aging in slightly less of a nutshell Metabolism
ongoingly causes damage whereas Damage only
eventually causes pathology This turns out to be
very useful
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Three paradigms for intervention Gerontology
Engineering Geriatrics Metabolism
Damage Pathology Claim only
the engineering approach can achieve
substantial extension of human healthspan any
time soon
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FAQ 2 Thats all a bit abstract and
theoretical, innit?
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FAQ 3 Yes, but thats just an analogy why
believe it?
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Metabolism Damage Pathology The
seven deadly things
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FAQ 4 How do you know that that list is
complete?
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20 years is a suspiciously long time to find
nothing out
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FAQ 5 Wont our solutions be very imperfect at
first?
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Life extension escape velocity
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FAQ 6 How close are we to fixing these things?
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We know how to fix all of them (in mice, in
principle!)

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• Why dont graveyards fluoresce?
• Some bacteria and fungi can break down really
  unusual things, and are used for bioremediation
  (a form of environmental decontamination). They
  break down rubber, TNT, PCBs, dioxins...
• Intracellular (often fluorescent) junk does not
  accumulate in the soil, even in areas rich in
  human remains. They are highly energy-rich, so
  microbes could live off them.
• Can micro-organisms capable of degrading
  lysosomal junk be isolated from the soil??

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• Steps to biomedical application
• Isolate competent strains select by starvation
• Identify the enzymes (mutagenesis, chemistry,
  genomics)
• Make lysosome-targeted transgenes, assay cell
  toxicity
• Test competence in vitro (more mutagenesis/selecti
  on)
• Construct transgenic mice, assay toxicity in vivo
• Test competence in disease models (apoE-/- mice,
  etc)
• Test in humans as for lysosomal storage diseases

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• Why mice are so important
• cheap (hence well-studied many versatile
  biotechnological tools available)
• short-lived (so life extension results can be
  obtained quickly)
• furry (so the public will take notice)
• Milestone Robust Mouse Rejuvenation (RMR) make
  normal two-year-old mice, expected to live one
  more year, actually live three more years

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• Time till robust human rejuvenation?
• Short answer hard to say, because
• humans already live long, so improving us is
  harder
• safety. Society doesnt like treatments that
  cure 90 of us but kill the rest, whereas in
  mice thats progress
• However, the 7 strands are just as comprehensive
  for human aging as for mouse aging. Thus
• if we had RMR today, RHR could be only 15 years
  away
• - if we translate pre-RMR work to humans at once,
  we may do it even faster. My guess 50 chance
  of RHR by 2030

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FAQ 7 Why didnt they say this on the TV the
other day?
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Biogerontologists
Peer review, short-termism
Media
Ballot box
Voters, shareholders
Government, industry
How can this logjam be broken???
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Fact to remember scientists will do anything
interesting for food
Biogerontologists
Philanthropy and Vision
Peer review, short-termism
Media
Ballot box
Voters, shareholders
Government, industry
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Proposal an Institute of Biomedical
Gerontology Remit to promote, co-ordinate and
fund the focused development of solidly
science-based rejuvenation biotechnologies such
as those I have discussed Basis 100m/year of
purely philanthropic funding would have a 90
chance of making enough progress in already
long-lived mice (therapy starting at 2/3 of life
expectancy giving three-fold greater remaining
lifespan), within 10 years, to change public
attitudes and start the real War On Aging
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FAQ 8 Well then, what are we all waiting for?
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Humanitarian context of the effort to cure aging
as soon as possible Fun Not fun
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Humanitarian context of the effort to cure aging
as soon as possible Many reasons are often given
why curing aging might have undesirable
consequences. One simple fact answers them
all Extending (healthy) lives saving
lives Failing to work to cure aging is no more
nor less than condemning 100,000 people every day
to die unnecessarily young on the basis of their
age. No possible downside of curing aging can
justify this.
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• Summing up
• Given adequate, focused funding, RMR will be
  doable in a decade with 90 probability
• RHR timeframe unknowable, but could be only
  5-10 years after RMR if there is aggressive
  translation to humans of pre-RMR progress
• Maybe longer, but so what?

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Lets roll
Email ag24_at_gen.cam.ac.uk Reprints, general info
http//www.gen.cam.ac.uk/sens/