The foreseeability of real antiaging medicine:

1
The foreseeability of real anti-aging
medicine Faith, rational design, and our duty to
abandon dogmatism just this once Aubrey D.N.J.
de Grey Department of Genetics, University of
Cambridge Email ag24_at_gen.cam.ac.uk Website
http//www.gen.cam.ac.uk/sens/
2
Structure of this talk 1) some unpleasant truths
about our rhetoric 2) human calorie restriction
and its emulation 3) an alternative with a
paradigm problem 4) why something must be done
3
Yes, Huber authorised this quote The difficult
political climate for a major life extension
research branch within the NIA is reflected by
recent email correspondence with Huber Warner,
Associate Director of NIAs Biology of Aging
Program, in which Warner wrote, our NIA Director
does not look forward to having congressmen ask
him during testimony sessions about whether our
goal is to extend the human life span. Mackey T,
Rejuvenation Research 7211
4
Was this wise, in the long run? Aging is not a
disease Add life to years, not just (!) years
to life one-hoss shay
5
What Jim Fries actually wrote Present data allow
calculation of the ideal average life span,
approximately 85 years. Chronic illness may
presumably be postponed by changes in life style,
. Thus, the average age at first infirmity can
be raised, thereby making the morbidity curve
more rectangular. Extension of adult vigor far
into a fixed life span compresses the period of
senescence near the end of life. Fries 1980,
NEJM 303130
6
The desperate discernment of compression of
morbidity
Manton 1997, PNAS 942593 Hodes testimony 2001
7
The desperate discernment of compression of
morbidity
Proportion of US over-65s disabled reduced by
25 !!! Hm, but proportion severely disabled
reduced by only 5
National Long-Term Care Survey (Manton 2001,
Fries 2003)
8
The desperate discernment of compression of
morbidity
Average time spent disabled reduced by 19 Time
spent severely disabled increased by 2
9
The desperate discernment of compression of
morbidity
Himsworth/Goldacre 1999, BMJ 3191338
10
Has this rhetoric served gerontology well?
Does this parity match our media exposure?
11

• A radical new theory politicians are not as dumb
  as they look
• Might it conceivably be that
• - politicians see no convincing evidence for
  sustained compression of morbidity?
• nor for biogerontologys potential to deliver it
  in the foreseeable future?
• rhetoric better supported by real data would
  elicit more positive reactions?

12
Are bioconservatives exploiting our fear of
discussing extreme life extension? Beyond
Therapy 311 pages Ageless Bodies 46
pages Biogerontologists who discuss foreseeable,
extreme life extension in the media
1 Biogerontologists who dont N-1, N
6 Interpretation our failure to educate the
public out of their ambivalence about real
anti-aging medicine gives bioconservatives a
foothold via which to turn people against ES
cells etc.
13
A modest proposal evidence-based rhetoric
Biogerontologists
Peer review, short-termism
Media
Ballot box
Voters, shareholders
Government, industry
14
A modest proposal evidence-based rhetoric
Philanthropy and Vision
Biogerontologists
Peer review, short-termism
Media
Ballot box
Voters, shareholders
Government, industry
15
A modest proposal evidence-based rhetoric
Philanthropy and Vision
Biogerontologists
Peer review, short-termism
Media
Ballot box
Voters, shareholders
Government, industry
16
How should we approach serious life extension?
Three sincerely-held views 1) Denial -- e.g.
Hayflick, Olshansky 2) Faith -- e.g. A4M, Miller,
Guarente 3) Rational design -- e.g. de Grey
17
Denial are the arguments robust? Proposals to
circumvent aging by replacing all parts as they
age with new or younger parts are unlikely to be
tenable .... When everything is replaced in a
car, it is no longer identical to the original.
In parallel with the dilemma of replacing all
parts in an aging inanimate object, doing so in
humans would result in a different
person. Hayflick 2004, JGBS 59A573
18
Denial are the arguments robust? slow
development at any age is viewed universally as a
serious pathology. If retarding the mental and
physical development of someone from birth to age
20 years for, say, 10 years, in order to gain a
decade of additional life is unattractive, then
slowing ones aging processes in later life will
not be attractive for the same reasons. Hayflick
2004, JGBS 59A573
19
Faith the hype and the reality A4M believes
that the disabilities associated with normal
aging are caused by physiological dysfunction
which in many cases are already? amenable to
medical treatment, such that the human life span
mean? max? can already? be increased, and the
quality of ones life improved as one grows
chronologically older. American Academy of
Anti-Aging Medicine
20
Faith the hype and the reality CR typically
produces in rodents an increase in mean and
maximal longevity of about 30-40. if begun at
weaning Similarly, mouse dwarf mutants, small
dog breeds -- prenatal CR?. Thus one can, with
some confidence, expect that an effective
antiaging intervention begun when?? might
increase the mean and maximal human lifespan by
about 40 Miller 2002, Milbank Q 80155
21
Proportionality the null hypothesis?
22

• Proportionality the null hypothesis?
• Okinawans versus same-age mainland Japanese
• half the dementia
• half the breast, colon and prostate cancer
• less than half the cardiovascular disease
• (just like bona fide CR in rodents)
• 3.4 times as many centenarians . i.e. a maximum
  lifespan 1.5 years more than mainland Japan.
  Mean lifespan was only 1.3 years more.

23
Evolutionary theory supports the data, not the
hype the extent of the evolutionary pressure to
maintain adaptability to a given duration of
starvation varies with the frequency of that
duration .... The pattern of starvation that the
weather imposes is suggested here to cause all
terrestrial animals, even those as far apart
phylogenetically as nematodes and mice, to
possess the ability to live a similar maximum
absolute (rather than proportional) amount longer
when food is short. de Grey 2005, Gerontology
51, in press
24
Rational design of real anti-aging medicine
de Grey 2002-2004, various
25
Impossibly piecemeal? An analogy
26
(No Transcript)
27
Response of the establishment an instructive
comparison Intervention to remove the
accumulating damage would sever the link between
metabolism and pathology, so has the potential to
postpone aging indefinitely. We survey the major
categories of such damage and the ways in which,
with current or foreseeable biotechnology, they
could be reversed. Such ways exist in all cases,
implying that indefinite postponement of aging
may be within sight. Aubrey de Grey, Bruce Ames,
Julie Andersen, Andrzej Bartke, Judy Campisi,
Roger McCarter
28
Response of the establishment an instructive
comparison I think it would be irresponsible to
publish the work as it stands, because it could
engender quite unwarranted optimism in
readers. Anonymous review of de Grey, Ames et
al Rae laments that he "has yet to hear a cogent
rejoinder " from the anti-aging skeptics in my
view it's because we skeptics have yet to see
anything even remotely convincing from de Grey
and his ilk, and don't wish to draw further
public attention to this fringe
movement Anonymous review of letter to JGBS
29
What is at stake? - Some large egos (including
mine) - Some chunk of todays modest budget -
100,000 lives per day that we delay success of
the right research
30
100,000 lives a day? Whos hyping now? My
axiom Extending healthy lives saving lives Old
people are people too Any challenge?
31
Escape velocity why saving lives is, if
anything, an understatement
de Grey 2004, PLoS Biology 2723
32
Whose duty is it to act?
Biogerontologists
Peer review, short-termism
Media
Ballot box
Voters, shareholders
Government, industry
33

• Conclusion
• Our traditional rhetoric has failed utterly
• If anyone can break the logjam, we can
• Instead, we are cravenly distorting biology
• This is costing thousands of lives each day
• Now is the time to take risks for life