In article <3602CE24.D5124557 at notarealaddr.ess>, bmdelaney at notarealaddr.ess
>>>>Thomas Mahoney wrote:
>> Some mice in the wild undoubtedly encounter
>> conditions very close to that achieved by calorie/dietary
>>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).
As to the mice, while I agree that is the most likely scenario but we are
looking for the extraordinary mouse that lived the longest who probably came
pretty close to mimicking CR as used in the Labs. to determine maximum life
The most commonly used name in Medline is dietary restriction. You will get
a lot more hits using that then even calorie restriction
>> 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.
We're splitting hairs here and the fact that there is a difference at all
makes this a legitimate area for research. The point I would make is that
all CR mice, of the same species, have the same life span. This means that
CR has not altered the underlying genetic cause of aging.
>> 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.
If your defining aging as a general decline in functioning of an organism
over time then the processes you cite have a very significant role in the
aging process. Estrogen replacement therapy does an excellent job of making
the body react as if it were still producing estrogen itself. The key here
is that although you are addressing an age related symptom you have done
nothing to alter the underlying cause of cellular aging nor to extend maximum
>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
This is a distinct possibility. But once again whatever adaptations made are
already part of our intrinsic life span. Utilizing procedures learned from
this process may allow us to live up to that limit but not beyond.
>>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
I won't rule out this possibility but even here we would eventually run into
the finite replicative capacity of the cells. At the best we're delaying the
inevitable, which is definitely worth investigating, but I'd still rather
eliminate the inevitable altogether!
>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
I've read numerous research papers on the subject and will stick with my
analysis that while they may, eventually, be effective in delaying some age
related symptoms they are doing little to increase our life span.
>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
There are some significant hurdles to overcome and many more years of
research to find out if a successful therapy can be developed and it's
probably worth the effort. But again I put in in the same class as research
into melatonin, growth factors, hormonal replacement etc... Let's keep this
research going but there are other, far more promising, lines of research
that deserve a higher priority.
>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.
Thank you for the compliment and I do hope this research turns out the way
Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.