X-Message-Number: 26500
From: "Michael C Price" <>
References: <>
Subject: Maximum lifespan can be extended
Date: Mon, 4 Jul 2005 09:15:18 +0100
Here's something I've just posted to the gerontology
research group, in response to an earlier post by one
of its founders to a journalist on the Wall Street Journal,
in response to an anti-aging article they had printed.
Hopefully my reply message makes sense on
its own -- if not see the previous post attached.
Cheers,
Michael C Price
http://mcp.longevity-report.com
http://www.hedweb.com/manworld.htm
***********************************
Dear Ms. Parker-Pope:
Don't be too discouraged by the argument that the existence of a species
maximum lifespan means that we can't easily extend human maximum lifespan.
In fact the opposite is true. Feeding rats, in separate experiments, extra
selenium and chromium (in larger amounts than they could possibly receive in
a natural diet) has extended their maximum lifespans beyond their species
maximum -- 15% longer with chromium, 43% longer (yes - 43%!) with selenium.
The latter would correspond to a human living to 174 years! And even more
if selenium and chromium acted additivity -- which we might expect for
biochemical reasons. References for these experiments are at the end of my
post.
There are a number of reasons why these experiments have been ignored by the
gerontological community, which I shall briefly list and answer:
a) the control laboratory rats were malnourished because their lab' diet
lacked essential nutrients. Answer: In the two experiments I refer to
above this was not the case -- but in any case this is irrelevant since the
treated animals exceeded the species maximum; we'd have to assume that *all*
laboratory *and* wild rats are malnourished for this to be a valid
criticism.
b) that humans are already getting enough of these minerals in their diet,
so these results will not extrapolate onto us. Answer: But extra selenium
is widely believed to reduce cancer incidence in humans and extra chromium
has been used to treat type II diabetes -- clearly our diets do not supply
the optimum amounts of these minerals.
c) humans live longer than rats, therefore our lifespans will be harder to
extend. Answer: This assumes that because humans have more optimised or
efficient metabolisms than rats (undoubtedly true) that therefore the
efficiency (and hence lifespan) can't be increased as easily -- but if this
was so then we would expect animals to be more prone to vitamin /mineral
deficiencies than the more optimal humans (not true, as far I can see) and
that therefore humans would not benefit from extra nutrients (such as
chromium and selenium). As we see in b) this isn't so. It seems as easy to
double the efficiency of a human's metabolism as it is a rat's or a
fruitfly's.
d) that the test animals ate less food (because it tasted horrible) and so
extended their lives by inadvertent or crypto- calorie restriction (which
is, of course, known to also extend maximum lifespan). Answer: in both
experiments the body weights were published. There was no significant
weight loss in the test animals (actually a slight gain in the selenate
group), so we can safely exclude crypto-CR as a confounding mechanism.
In conclusion, we have every reason to think that we can very dramatically
and very easily extend human maximum lifespan. Of course not everybody will
make the maximum lifespan. We need also to square the survival curve; for
this large doses of B-vitamins have proven very effective. But that'
another story. Also we have good reasons for thinking that other minerals
will also retard aging. Zinc, for example, has reversed the age-related
shrinkage of the thymus gland in mice and extended their maximum lifespan
(relative to controls). Magnesium is also a mineral that might be
effective -- although no lifespan test has been conducted yet. All in all
we might expect to live as long as the bow head whales that Dr Stephen Coles
mentions.
Cheers,
Michael C Price
PS here are the references, with a few quotes and my own comments:
Chromium:
1) Life Span is Increased in Rats Supplemented with a Chromium-Pyridine 2
Carboxylate Complex. Gary W Evans & Lynn K Meyer in Advances in Scientific
Research 1994 1(1) - this article is hard to get hold of (the journal
rapidly folded, I believe), but it specifies some extra information beyond
the other derivative references, such as the body weights of the different
groups not being significantly different at death (which excludes the
possibility of crypto-CR as a life-extending mechanism).
The above reference is hard to obtain (I have a paper coipy and can scan in
and send if required); here are some derivative references about the same
experiment:
2) Composition and Biological Activity of Chromium-Pyridine Carboxylate
Complexes. GW Evans and DJ Pouchnik, Journal of Inorganic Biochemistry 49,
pg 177-187 (1993). PMID: 8433089
Describes the action of dietary chromium picolinate (relative to chromium
chloride and chromium nicotinate) in reducing glycation & plasma glucose
levels in rats as they aged.
3) Longevity effect of chromium picolinate--'rejuvenation' of hypothalamic
function? McCarty MF in Med Hypotheses 1994 Oct;43(4):253-65 PMID:
7838011
"The first rodent longevity study with the insulin-sensitizing nutrient
chromium picolinate has reported a dramatic increase in both median and
maximal lifespan.." Gives additional information about the
Evans-Meyer-Pouchnik chromium picolinate experiment on rats: Cohort maximum
lifespan (last survivor) was 48 months, extending the previous species
maximum by 15% to give a total maximum lifespan increase of 26%.
4) Chromium picolinate increases longevity. Evans GW, Meyer LK in AGE (the
Journal of the American Aging Association) Oct 1992; 15(4), 134.
5) Chromium Picolinate. Gary W Evans, (1996) ISBN 0895299119.
Gives additional information about the Evans-Meyer-Pouchnik chromium
picolinate experiment on rats: Mean lifespan extension of 27%. However,
the strain of rats used may have been pre-diabetic.
5b) The Longevity Factor: Chromium Picolinate. RA Passwater, (1993), ISBN
0879836199.
Selenium:
6) Selenium and tellurium in rats: effect on growth, survival and tumors.
Schroeder HA, Mitchener M in J Nutr. 1971 Nov; 101(11): 1531-40 PMID:
5124041. The selenate dose used (3ppm) was toxic (carcinogenic); despite
this the mean LS was extended by 9%, maximum cohort LS by 48%., which at 60
months beat the previous species maximum of 42 months by 43%. (Selenite at
3ppm was highly toxic and not pursued.) The ratio of max cohort LS /
control mean LS was 2.25. (cf: control max/mean LS = 1.52) The controls
received 50ug/kg selenium / wet diet weight.
Zinc:
7) Presence of links between zinc and melatonin during the circadian cycle
in old mice: effects on thymic endocrine activity and on the survival.
Mocchegiani E, Santarelli L, Tibaldi A, Muzzioli M, Bulian D, Cipriano K,
Olivieri F, Fabris N. in J Neuroimmunol. 1998 Jun 15;86(2):111-22. PMID:
9663556
"The beneficial effect of the links between zinc and melatonin on thymic
functions during the circadian cycle, may be extended to a prolonged
survival in aging, where, however, zinc may be more involved [than
melatonin]."
Median lifespan extension 39%; max lifespan extension 10% (relative to the
controls) for the zinc sulphate mice
----- Original Message -----
From: L. Stephen Coles, M.D., Ph.D.
To:
Cc: Gerontology Research Group ;
Sent: Wednesday, June 22, 2005 6:27 AM
Subject: [GRG] Special Section in Today's Wall Street Journal
Ms. Tara Parker-Pope, Health Writer
The Wall Street Journal
New York, New York
Tuesday, June 21, 2005; 10:20 PM PDT; Los Angeles, Calilfornia
Dear Ms. Parker-Pope:
I read your recommendations on heath matters every week, and am
generally impressed with the quality of your work. Over the last few years,
I have communicated regularly with other members of the WSJ staff like
Sharon Begley and Antonio Regalado rather than you, because they tend
to focus more on research than on day-to-day clinical issues. I was also
interviewed for a front-page Section "A" story by Jeff Zaslow [1]. Also, I
saw in yesterday's WSJ, Section R, is devoted to "The Secrets of Successful
Aging: What Science Tells Us about Growing Older and Staying Healthy"
in which you cited one of our statistics "65" in the Table on page R3 "By
the
Numbers."
However, I have to register a complaint... You have made it harder
for me to overcome the resistance of the public in deluding themselves
that there is anything they can do to live significantly longer than they
otherwise would. The illusion is that stress reduction (will keep your
telomeres long for a longer time, or whatever), exercise, nutrition, weight-
reduction, and so forth can really make an impact, and that in some sense
"there is hope." Well, I'm sorry. I don't expect that anyone will live
longer
than Madam Jeanne Calment did (122) in our lifetimes, no matter what we
do (short of making a really dramatic break though in genetic engineering
that changes "the rules of the game"). Why? Because the phenotype of
Maximum Lifespan for any mammalian species is built into the genotype
(genome) of that species. We are pretty much at the outer edge of
shrews, mice, rats, bats, dogs, cats, horses, chimps, and elephants, with
the single exception of bow whales (who are acknowledged by zoologists
to live to ~220 years).
I have devoted the last 40 years of my life to understanding the
aging process in all sexually-reproducing organisms on this planet,
including humans as a special case, and I am sad to report that there is
no amount of stress reduction that could ever get us into the bow-whale
class. It's simply not in our genomes, as a species.
It's not that you said anything particularly wrong. Each one of the
scientists who is strongly driven (by ego) to discredit any competing
theory of the aging process, other than the one that he or she is
proselytizing at the current moment, has lots of data to support their
position -- whether it's caloric restriction, growth hormone,
progeria(s), free radicals, telomeres, or whatever. Each of these
scientists represents a "card" in a "deck." The job of the reporter is to
shuffle the deck and repackage it in language that can be understood by
ordinary folks. None of the cards that you have presented
is mis-characterized, and as a reporter, not an inventor of new cards, you
explained things well (in non-technical language). The problem is with your
shuffling. Your self-proclaimed originality was that you wanted to put
"stress reduction" toward the top of the deck and push "inheritance of
longevity
from one's parents" down toward the bottom. I suppose because "stress"
is something one can do something about, while one no longer has the option
to re-choose one's parents, and so the die was cast,
so to speak, leaving one's longevity to "fate" rather than within one's
control. Well, I'm sorry to report that the original shuffling was probably
more correct than yours; so there you have it. We really don't know
what the "real" shuffling should be since some of the cards are still
missing
from our deck, due to a lack of imagination by the scientific community in
general and biogerontologists in particular.
The Swedish twin study that you cite stating that "only about 30 percent of
longevity can be attributed to genes" is probably true as studies go, but
misrepresents the importance of genes in "the oldest old." (There are
virtually
no twins [identical or fraternal] when you get out into the Supercentenarian
class, so all bets are off in terms of making a valid statistical argument).
My
own guess, based on the statistics that we have accumulated for the last
five
years together with the interviews of maybe ten Supercentenarians and one
autopsy that I've done in the Pathology Department at UCLA), is that our
DNA makes an 80 to 90 percent contribution in making it to Supercentenarian
status. These extraordinary outliers live as long as they do, not because of
any conscious stress-reduction program or failure to indulge in bad habits
(which many do, like smoking, drinking heavily, or both). They live as long
as they do in spite of not because of their bad habits.
But they almost always have long-lived parents and siblings. So there! I'm
sure that won't make your readers feel any better, but that's the way it is.
My final argument is that every single person who has any chance of
living through the next 15 - 20 years without dying of a pre-existing
chronic condition and really want to live a very long time should instantly
adopt an intense program of nutrition, dietary supplements, exercise, and
stress reduction, because real anti-aging interventions, based on knowledge
of stem-cell technology and comparative genomics, may come in just in that
time frame. It would be a real shame that because you did something
foolish and died before you could benefit from these scientific discoveries,
which I believe to be just around the corner (in terms of the "long eye of
history"),
that you suffered an opportunity cost of truly profound dimensions. This
IS a really big deal that your readers should know about.
Sincerely yours,
Steve Coles
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