IUBio Biosequences .. Software .. Molbio soft .. Network News .. FTP

Antiaging Research Priorities [was Re: Major Criticisms of

Brian Manning Delaney bmdelaney at notarealaddr.ess
Fri Sep 18 16:18:29 EST 1998



Thomas Mahoney wrote:
> In article <3602A142.514CD024 at notarealaddr.ess>,
> bmdelaney at notarealaddr.ess says...
>>Thomas Mahoney wrote:
>>> In article <36021FF5.2CF95D48 at notarealaddr.ess>,
>>> bmdelaney at notarealaddr.ess says...
>>>
>>>> Thomas Mahoney/ Excelife wrote:
>TM/E: Quite correct. Mice in the wild undoubtedly
>TM/E: encounter periods where food is scarce and the
>TM/E: effects seen in CR are likely an adaptive
>TM/E: response to these conditions. Thus the actual
>TM/E: life span of the mice is that seen in CR.
>>>>
>BMD: I'm not sure how this way of looking at it is helpful.
>>
>>[....]
>BMD: Take another example. Say we had evolved a mechanism whereby
>BMD: eating a certain substance found in a now rare plant turns
>BMD: on telomerase in enough cells, in the right way, to slow
>BMD: aging. No one has been known to eat the substnce because our
>BMD: dietary habits over the last few centuries have precluded
>BMD: its consumption. But suddenly we discover it, and people
>BMD: start taking it and living to be 140 years old. Since this
>BMD: ability to age slowly under the conditions of the presence
>BMD: of this substance is an evolutionary adaptive response,
>BMD: would you say people living to 140 by means of this
>BMD: substance aren't extending their life span?
>>
>>> Here you changed the premise. By stating that
>>> they lived to 140 you have, by definition,
>>> increased the maximum life span in humans.
>>
>> I don't get it. You seem to be operating with two
>> definitions of maximum life span: 1) the longest an animal
>> (of a particular species) can live under conditions like any
>> of those which originally selected for an adaptive
>> anti-aging response (see your quote, above); and 2) the
>> longest any member of a species has lived.
>> 
>> If we adopt (1), then you are wrong that I've changed the
>> premise. The point of the example was to show just that.
>> 
>> As for (2), I can't see how this definition ever would be
>> useful. If I invent a drug that lets people live to 180,
>> then, under this definition, I can't say that the drug
>> extends human maximum life span after the first person has
>> taken it. Doesn't seem helpful. Wouldn't we want to say the
>> second and third people taking it are also living beyond the
>> human maximum life span? The second and third aren't
>> BREAKING RECORDS, sure, but that's something different.

> The definition of life span provided by James, "maximum
> lifespan observed in the wild without
> researcher intervention", is appropriate and
> very close to what I've been trying to say.

James' definition is the one commonly used by researchers,
and makes a lot of sense. (This is essentially my #1
definition above.)

> Some mice in the wild undoubtedly encounter
> conditions very close to that achieved by calorie/dietary
> restrictions.

Only for brief periods. For longer periods, they would tend
to be on FR (food restriction), not CR. FR extends life
slightly, but not nearly as much as CR (also called by
Walford in his first book a "high/low" diet -- a bunch of
other confusing names have come into use recently).

> Full laboratory controlled CR may
> provide a slight incremental increase in life
> span for mice but that's more  an artifact of
> the experiment than any fundamental break through.

No, all evidence indicates that it provides much more than
an incremental increase in life span, even compared with
rodents in the wild that experience periodic FR (and perhaps
even periodic CR) during droughts, etc.

> In humans the maximum lifespan observed in the
> wild without researcher intervention is 122 years.

(Technically, some would argue that anyone living beyond 115
is a statistical "outlier," but that's a minor point.)

> In your examples if the treatment used allows a
> person to live significantly  longer than 122
> years then the treatment has altered the basic
> genetic control of the aging process and you
> will probably be receiving a Nobel  Prize.

This is where I don't get your reasoning. It's almost as if
you're ruling out "nurture's" role in aging, or ruling out
the existence of a broad range of environmental conditions
under which different genes can find expression. Why
couldn't it be the case, for example, that 1) as a response
to conditions of food scarcity, mammals (and perhaps all
living things) evolved the ability (i.e., developed the
GENETIC changes necessary for the ability) to retard aging
until more food is available, and 2) humans who have lived
to 115-120 haven't had these genes expressed (or haven't had
them expressed in the right way) consistently enough to live
beyond ~120?

In other words, I see no evidence to rule out the follow
theory: Humans on fairly strict CR started in early
adulthood could live 20-35% longer than the maximum life
span as we've defined it. Some would argue that those living
being 105 or so actually did practice a mild, inconsistent
(and inadvertent) CR. (Call it a mild, inconsistent
"researcher intervention".) If so, than we could expect CR
to get us only to 126-142 or so. If not, CR could get us to
146-162. Either way, I'd call that an extension of maximum
life span.

But you apparently feel there's little reason to believe
that CR will work in a wide range of animals. I'd like to
know why. It's been tested in a broad range of organisms,
and works dramatically in all of them, with a few irrelevant
exceptions (like the amoeba, which becomes immortal if
overfed). James pointed to the primate studies. In addition,
I'd point to studies which show that a CR-like diet, in
humans, radically alters biomarkers in a way that suggests
aging is being retarded (lowered fasting glucose, for
example). (Search Medline for /Walford/ to see a few of
these studies.)

To be sure, we don't know for certain that CR will work in
humans, but it seems extremely unlikely that it won't work
at all.

As I said before, I very much like your company's plans, and
wish you the best. But I think your belief that attempts to
develop CR-mimicking drugs aren't likely to pan out, or that
they aren't likely to pan out in a way that significantly
extends what most people would consider the human maximum
life span, is unwarranted.

Best,
Brian.



--
Brian Manning Delaney
My email address is here:
http://xyz.uchicago.edu/users/bmdelane/email4.htm
[Wrists: "Leave unambiguous typos."]
Note: All statements in this article are in jest; they
are not statements of fact.
"Mein Genie ist in meinen Nuestern." -Nietzsche.
** Please do not CC your Usenet articles to me. I'll find
them.



More information about the Cellbiol mailing list

Send comments to us at biosci-help [At] net.bio.net