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Antiaging Research Priorities [was Re: Major Criticisms of The

Excelife excelife at earthlink.net
Fri Sep 18 04:52:12 EST 1998

In article <36014B75.73282A9 at nospam.com>, james at nospam.com says...
>> First I've seen numerous posts, (but not from Tom), that state that CR is 
>> one of the very few methods of extending any organisms life span.  This is
>> patently not the case.  The appropriate way to phrase this phenomena is  
>> that "Caloric restriction has been demonstrated to retard aging processes 
>> and extend *maximal* life span in some species."
>> While CR mice do live longer than mice whose diet is not restricted they 
>> live no longer than than other mice on CR.  Their life span has not been 
>> increased by CR only their life expectancy has been increased.
>I know someone already said "huh?" to this, and I'd like to second the 
>motion. I'm not trying to be whatever...  I really have no idea what this is 
>supposed to mean.  I assume that it has something to do with an average 
>versus maximum age argument that you are trying to make.

Let me spell it out.  Mice have a genetically fixed life span, probably 
determined by the short telomeric length on some chromosomes, (I threw that 
in just to keep Tom happy:-).

The ages shown below are approximations and vary significantly depending on 
the type of mice studied but the relationships between the ages demonstrate 
my analysis.

Laboratory mice fed ad libitum or an unrestricted diet live approx. 2.5 years

CR mice on a diet at 60% of ad libitum live approx. 3.5 years.

Wild mice who eat when they can and often go without food live approx. 3.0 

Since no mice live longer than 3.5 years then the genetically determined 
*maximal* life span is 3.5 years.

CR gets the mice up to their maximal life span but cannot exceed it! 

>Regardless, I do not believe that you are correct.  Caloric restriction has 
>beenshown to increase both average and maximal lifespan (see Yu et al. 1990, 
>Yu et al. 1982, Sohal R et al. 1996, Weindruch R, 1996, etc.)  A rough 
>calculation from looking at the graph in the Yu paper (which used 115 rats 
>in each group) shows about a 37% increase in maximum lifespan and more like 
>50% increase in average life span.  So if you're saying that everyone has 
>changed their minds in the >past two years please provide references.

I'm suggesting that their definition of life span is based on that seen in 
laboratory mice fed ad libitum, ie; 2.5 years.  This is not the same 
definition we commonly use for human life span. In humans it is defined as 
the longest any one can possibly live.  Most people reading these papers 
don't realize that and think a major breakthrough has occurred when that is 
not the case.

The maximal life span in mice is approx. 3.5 years and the maximal life span 
for humans is 120 years. CR mice live close to their maximal lifespan and if 
we could get more people to live close their maximal life span through 
research into CR that would be commendable. 

>> This relegates this research to the same class as vaccines, antibiotics,
>> hormonal replacement and dietary supplements. It is valid research and >> 
could possibly achieve some significant increases in human life expectancy >> 
but has little if any relation to extending the human life span.

>And even if you were correct and caloric restriction only increased average 
>life span, placing a high priority on the research would still be 100% 
>justified. There is a very large difference in average life span versus 
>maximum life span inhumans.  For round numbers let's use 80 for average 
>lifespan and 120 for maximum lifespan.  That means that the worst case 
>scenario is that caloric restriction gives you another 20-40 years (on 
>average), instead of allowing you to live beyond 120.

Possibly, assuming that the adaptive reponse seen in CR mice is at all 
applicable to the way that humans respond to a restricted diet.  This has not 
been demonstrated by the research to date.  

>Perhaps you are saying "But a life expectancy of 100 to 120 years in not
>satisfactory to me, so I will research things that, while they may be much 
>less certain, have a chance of extending my life much more than caloric 
>restriction can."

If this research, which has been going on for quite some time, showed promise 
that we could extend human life expectancy by 20 years or more I would be 
behind it 100%.  The results aren't there!  There's not even a suggestion 
that this research will achieve these results any time soon.  Even the basic 
theory as to how or why it might work has not been established.  The problems 
associated with this research are close to insurmountable.  In mice it has 
not been effective in older mice, the beneficial effects of CR have not been 
demonstrated on species closely related to mice let alone man and at best it 
will only improve quality of life.

>Is anyone thinking that?  Wrong.  Because in those extra 20 to 40 years that 
>caloric restriction will allow you, if history is any indication, you will 
>have time to witness (and take advantage of) vast scientific progress that 
>we cannot even guess at right now.  I would say that if you knew right now 
>that you could live to be 120 with caloric restriction, your prospects for 
>living well beyond that (by taking advantage of the next 50-100 years of 
>scientific advancement) are pretty good.  Very good in fact.  Look at where 
>we were 50 years ago.  We didn't know what a restriction enzyme was.  We had 
>only recently discovered the structure of DNA.  And personal computers we 
>not due to exist for 30 years.  50 years is like night and day in science.  
>And if you happen to be fairly young and might expect to have almost 100 
>years from today...

I agree completely.  But lets work on something that has a chance of getting 
us there.

>> Dr. E.J. Masoro, a major researcher in the field of CR at The University 
>> of Texas Health Science Center at San Antonio, has suggested two possible
>> mechanisms. The first is "the altered metabolic characteristics of glucose
>> fuel use and of oxidative metabolism" and the second "relates to the     
>> enhanced ability of the rodents restricted in food intake to cope with >> 
challenges,which in turn has been linked to the glucocorticoid system and >> 
to the heat-shock protein system".
>> Any suggestions on how to proceed?
>Yep.  As I have already mentioned let's stop shooting in the dark and find 
>out exactly what genes are being up or down regulated by caloric 
>restriction.  We can do it now (using DNA chip technology), with the 
>incomplete genome sequence (which means we will probably have to do it again 
>later) and at least that will give us something to work with for the next 5 
>years of so until we have the complete sequence.

As I've mentioned previously this is exciting technology that can give us 
some very substantial insights into what is happening to the genes during 
various stages of development.  I'm not that familiar with the technological 
end of this research, (which is why I snipped the last part of your post), 
but I have seen some of the results it can achieve.  They are impressive and 
regardless of the "theory" being studied the information gleaned will benefit 
all aging research.

Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.

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