Strategies for Engineered Negligible Senescence SENS:

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Strategies for Engineered Negligible Senescence
(SENS) How foreseeable bioengineering can
comprehensively reverse human aging Aubrey
D.N.J. de Grey Department of Genetics, University
of Cambridge Website http//www.gen.cam.ac.uk/se
ns/ Email ag24_at_gen.cam.ac.uk Questions, reprint
requests etc. always welcome
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• Structure of this talk
• definitions, milestones and strategies
• why the War On Aging may be only a decade away
• why it may be a very short war
• why we may also win the peace very quickly
• what we can, and should, be doing to make this so

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Definitions Senescence (Anon) the process that
progressively reduces an organisms remaining
life expectancy Negligible senescence (Finch
1990) absence, in a population, of a degree of
senescence sufficient to be statistically
detectable by examining its age
distribution Engineered negligible senescence
(de Grey 1999) the biotechnological conversion
of a population that exhibits statistically
detectable senescence into one that does not
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A brief history of engineered negligible
senescence (ENS)
t1 t2 t3 t4 t5 t6 late-onset human ENS (LOHENS)
ubiquitous
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• Q What do people need, to start caring about
  life extension?
• A Laboratory life-extension results that they
  can identify with
• big
• in mammals
• treatment initiated late in life

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A brief history of engineered negligible
senescence (ENS)
t1 important components of human aging all
known to be so t2 feasible plan for Robust
Mouse Rejuvenation described t3 RMR developed
remaining LE of 2yo mice trebled LOHENS
widely seen as foreseeable, WOA begins t5
LOHENS developed, some people are in clinical
trials t6 late-onset human ENS (LOHENS)
ubiquitous
t4
t5
t6
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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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2. Why the War On Aging may be only a decade
away
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Metabolism Damage Pathology The
seven deadly things
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20 years is an extremely long time in science to
find nothing out
We can thus be highly confident that t1 1982
important components of human aging all known
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t2 is now t2 feasible plan for Robust Mouse
Rejuvenation described IABG 10 Cambridge, UK,
Sept 19-23 2003
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A brief history of engineered negligible
senescence (ENS)
t1 1982 important components of human aging
all known to be so t2 2002 feasible plan for
Robust Mouse Rejuvenation described t3
????-???? RMR developed remaining LE of 2yo
mice trebled t4 ????-???? LOHENS widely seen
as foreseeable, WOA begins t5 ????-???? LOHENS
developed, people are in clinical trials t6
????-???? late-onset human ENS (LOHENS)
ubiquitous
????-????
????-????
????-????
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A brief history of engineered negligible
senescence (ENS)
t1 1982 important components of human aging
all known to be so t2 2002 feasible plan for
Robust Mouse Rejuvenation described t3
2012-2022 RMR developed remaining LE of 2yo
mice trebled t4 2015-2027 LOHENS widely seen
as foreseeable, WOA begins t5 ????-???? LOHENS
developed, people are in clinical trials t6
????-???? late-onset human ENS (LOHENS)
ubiquitous
2015-2027
????-????
????-????
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3. Why it may be a very short war
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How long will the war on aging last? t5 t4
5-???y LOHENS developed, people are in clinical
trials
5-???y
t1 1982 important components of human aging
all known to be so t2 2002 feasible plan for
Robust Mouse Rejuvenation described t3
2012-2022 RMR developed remaining LE of 2yo
mice trebled t4 2015-2027 LOHENS widely seen
as foreseeable, WOA begins t5 2020-???? LOHENS
developed, people are in clinical trials t6
????-???? late-onset human ENS (LOHENS)
ubiquitous
2015-2027
2020-????
????-????
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Q Arent there lots of aspects of human aging
that mice dont get? A yes -- but as soon as
something is implemented in mice, it can be
translated incrementally to humans to suitably
humanised mice, to dogs, to monkeys. With
late-onset interventions (and ample funding --
remember WOA is in progress at this point), this
is relatively quick.
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Q How could LOHENS (complete control of human
aging) possibly arrive so soon after WOA
begins? A bootstrapping We age very slowly.
Even a doubling of the remaining life expectancy
of 60-year-olds, such that at 80 they are still
physiologically 60 but then they decline at
present rate, allows 20 years (a very long time
in science!) to develop a doubling of the
remaining life expectancy of those same people at
80, etc, etc.
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Q But wont life-extended people be at risk
from yet-unknown causes, which will take time to
research/cure? A monkeys It is very
unlikely that humans will ever suffer at age N
from anything that monkeys dont get by at least
age N/2 given the same medical care. We will
thus have a long (and increasing!) lead time to
develop cures for as yet unknown age-related
problems before any human ever exhibits them.
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4. Why we may also win the peace very quickly
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How long will it take to win the peace? t6 t5
5-100y late-onset human ENS (LOHENS) ubiquitous
5-???y
t1 1982 important components of human aging
all known to be so t2 2002 feasible plan for
Robust Mouse Rejuvenation described t3
2012-2022 RMR developed remaining LE of 2yo
mice trebled t4 2015-2027 LOHENS widely seen
as foreseeable, WOA begins t5 2020-???? LOHENS
developed, people are in clinical trials t6
2025-???? late-onset human ENS (LOHENS)
ubiquitous
2015-2027
2020-????
2025-????
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With infinite funds and infinitely many medical
personnel... the situation would be simple
enough nothing would stop us from providing
rejuvenation therapy for free, to everyone,
without delay. Arguments stressing the dangers
of doing so (overpopulation, boredom, tyrants
reigning forever) will be unpersuasive, to say
the least. But funds and expertise will be
finite...........
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The history of availability of medical care not
a useful precedent Difference 1 public
pressure will force the compulsory purchase (for
extremely large sums) of any patent that risks
retarding universal access Difference 2 in the
long term, rejuvenation therapy pays for itself,
however expensive it is, by wealth produced
thereafter by the beneficiary
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Inference the sooner we start setting funds
aside and training more medics, the
better Danger un-meetable demand (starting at
t4, the start of the WOA) for traditional medical
care to help people make the cut Danger strife
between wealthy immortal nations and poor
subhuman nations in a post-9/11 world
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5. What we can, and should, be doing to make
this so
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The curious case of the catatonic
biogerontologists Straw polls at IABG 10,
22/9/03 1) Most BGs think I might be right
about t3 2) Most BGs think we shouldnt discuss
t5, t6 Are these views compatible?
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Will WOA begin in one decade, or two?
t3 t2 10-20y RMR developed remaining LE of
2yo mice trebled t4 t3 3-5y LOHENS widely
seen as foreseeable, WOA begins
3-5y
Biogerontologists
Peer review, short-termism
Media
Ballot box
Government, industry
Voters, shareholders
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Strategy 1 break down the wall of comfortable
academic fallacies de Grey 2003, Exp. Gerontol.
38 927-934 Theres no evidence that aging can
be appreciably altered Theres so much in
biology that we dont remotely understand Its
more important to compress morbidity Tyrants
will reign forever treatments will only be for
the rich The population crisis would be
unmanageable Replacing brain cells would
endanger continuance of identity We must say
nothing to cause optimism until we succeed in
mice Well be seen as charlatans failure will
rebound as loss of funding
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Strategy 2 remember that 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 open the WOA floodgates
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• How many billionaires
• are there in the USA?
• - are friends (or friends of friends) of at least
  one person in this room?
• are needed to fund the IBG as just described?

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The Methuselah Mouse Prize
Biogerontologists
Philanthropy and Vision
Peer review, short-termism
Media
Ballot box
Voters, shareholders
Government, industry
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The Methuselah Mouse Prize
FAME
Biogerontologists
Philanthropy and Vision
Peer review, short-termism
Media
Ballot box
Voters, shareholders
Government, industry
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http//www.methuselahmouse.org/
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A closing word to anyone who doesnt believe my
timescales
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Lets roll
Website http//www.gen.cam.ac.uk/sens/ Email
ag24_at_gen.cam.ac.uk