Why does calorie restriction reduce the rate of aging?

Robert Bradbury rbradbur at hardy.u.washington.edu
Wed Aug 26 23:29:45 EST 1992

In article <Aug. at pilot.njin.net>
  macko at pilot.njin.net (Peter C. Macko) writes:
> bradbury at sftwks.UUCP (Robert Bradbury) writes:
>  Have there been any studies that have varied the sources of the
>calories fed to CR animals?  

Yes, quite a few in fact.  The basic conclusion is that in general CR works
without regard to the fat/carbohydrate/protein proportions in the diet.
High fat or protein diets seem to be decrease longevity, perhaps because
the storage of fat in adipose tissue is more efficient than converting
carbohydrates/protein to fat for storage (i.e. fat provides more "usable"
calories than carbohydrate/protein) and high protein intake stresses
the kidneys and to a lesser degree the liver due to the nitrogen elimination
requirements.  One can get a small difference (perhaps 5-10% increase in LS)
by consuming a high carbohydrate/low fat/protein diet but this is small
compared with the 20-30% increase in LS you could get on a high fat/protein
diet if the calories are restricted by 40%.  Of course the best situation
is a high carbo diet with 40% less calories.

>  Is there any measurable difference in the metabolic rates of CR animals
>and animals on a "normal diet" throughout different points in their 
>lifespans before the normal diet animals reach "old age"?

A decrease in metabolic rate was for a long time the suspected mechanism
of increasing the life span.  That has been disproven.  After a period
of adaptation in which MR may be decreased, the metabolic rate per unit
of lean body tissue returns to normal.  (This is a key point since it
indicates that the metabolism associated with adipose tissue which is
diminished in CR animals may have decreased significantly.)  There is
a slight decrease in temperature at various times of the day but this
doesn't seem to reduce O2 consumption.  This may imply a shift
in energy use from thermogenesis to DNA/protein repair.

> Are youthful
>animals on a normal diet more energetic  then those on a restricted diet?

No, physical activity is the same, certainly lifetime activity is increased
CR animals due to the lifespan extension.

>At what point in life, if any, does this get reversed?

Physical activity is the same.  The decline in function happens at the
very end of the life of CR animals just as in the AL (ad libitum fed)
animals except it begins at an older age.  One has to look at the death/
disease incidence curves to understand this.  What it looks like is that
someone inserted a number of years into the middle of the survival curve.

> Should the CR diet
>start later in the animal's life, does it have the same, somewhat reduced,
>or no impact at all?  

Starting CR during childhood or puberty prolongs that phase of growth.
Starting CR in adulthood has most of the impact of starting it in puberty
or childhood.  It is almost as if once you reach adulthood a clock starts
ticking and CR reduces the clock's rate.  Of course the later in adulthood
one begins CR the smaller the impact.

>So if there are any good scientific references on this subject and the
>studies done to date please recommend them.

Books/articles by Roy Walford or Richard Weindruch which I've mentioned
already are the best place to start.   Some recent reviews in the last
couple of years include:
  Nutr-Rev 49(9):278-80
  Mut-Res  250(1-2):17-24
  Hematol-Oncol-Clin-North-Am 5(1):79-89
  Basic-Life-Sci 53:351-361
  Proc-Soc-Exp-Biol-Med 195(3):304-311

Robert Bradbury		uunet!sftwks!bradbury or rbradbur at u.washington.edu

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