Re: Born to run; the story of the PEPCK-C(mus) mouse.
- From: Taka <taka0038@xxxxxxxxx>
- Date: Wed, 16 Apr 2008 19:24:55 -0700 (PDT)
On Apr 16, 5:37 pm, Olafur Pall Olafsson <olafurp...@xxxxxxxxx> wrote:
Remarkably, as reported in the full text the PEPCK-C(mus) mice lived
almost 2 years longer than the controls and had normal litters of pups
at 30-35 months of age.
Biochimie. 2008 Apr 1 [Epub ahead of print]
Related Articles, Links
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Born to run; the story of the PEPCK-C(mus) mouse.
Hanson RW, Hakimi P.
Department of Biochemistry, Case Western Reserve University School
of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4935, United
States.
In order to study the role of the cytosolic form of
phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-C) in
skeletal muscle, PEPCK-C(mus) mice were created by introducing the
cDNA for the enzyme, linked to the human alpha-skeletal actin gene
promoter, into their germ line. Two founder lines generated by this
procedure were bred together, creating a line of mice that have
9.0units/g skeletal muscle, as compared to 0.080units/g in muscle from
control animals. The mice were more active than controls in their
cages and could run for up to 5km, at a speed of 20m/min without
stopping (control mice run for 0.2km at the same speed). Male PEPCK-
C(mus) mice are extremely aggressive, as well as hyperactive. During
strenuous exercise, they use fatty acids as a fuel more efficiently
than do controls and produce far less lactate than do control animals,
perhaps due to the greatly increased number of mitochondria in their
skeletal muscle. PEPCK-C(mus) mice also store up to five-times more
triglyceride in their skeletal muscle, but have only marginal amounts
of triglyceride in their adipose tissue depots, despite eating 60%
more than controls. The concentration of leptin and insulin the blood
of 8-12 months of PEPCK-C(mus) mice is far lower than noted in the
blood of control animals of the same age. These mice live longer than
controls and the females remain reproductively active for as long as
35 months. The possible reasons for the profound alteration in
activity and longevity caused the introduction of a simple metabolic
enzyme into the skeletal muscle of the mice will be discussed.
PMID: 18394430 [PubMed - as supplied by publisher]
Related Links
* Overexpression of the cytosolic form of phosphoenolpyruvate
carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in
the mouse. [J Biol Chem. 2007]
* Phosphoenolpyruvate carboxykinase and the critical role of
cataplerosis in the control of hepatic metabolism. [Nutr Metab (Lond).
2005]
* Metabolic effects of developmental, tissue-, and cell-
specific expression of a chimeric phosphoenolpyruvate carboxykinase
(GTP)/bovine growth hormone gene in transgenic mice. [J Biol Chem.
1990]
* Regulation of phosphoenolpyruvate carboxykinase (GTP) gene
expression. [Annu Rev Biochem. 1997]
* A mutation in the peroxisome proliferator-activated receptor
gamma-binding site in the gene for the cytosolic form of
phosphoenolpyruvate carboxykinase reduces adipose tissue size and fat
content in mice. [Proc Natl Acad Sci U S A. 2002]
* >> See all Related Articles...
Here is a quote from the full text article:
"A second surprising result was the apparent extend longevity of the
PEPCK-Cmus mice; they lived almost 2 years longer than the controls
and had normal litters of pups at 30-35 months of age (most mice stop
being reproductively active at 12-18 months). We use the word
"apparent" because we have not as yet carried out a detailed aging
study, involving multiple mice, which are followed at regular
intervals over their lifetime; this type of study is currently in
underway in our laboratory so hopefully we will be able to state
unequivocally that the PEPCK-Cmus mice do live longer than controls.
However, the available evidence is strong enough to warrant some
speculation as to why these mice have such an extended life span. This
is especially important since the mice violate one of the pillars of
aging research, namely that limiting food intake increases longevity.
This general principle is supported by studies with species from flies
to rats, and seems well grounded in the literature. If correct, the
results with the PEPCK-Cmus mice imply that it is not the number of
calories consumed, but what happens to these calories one they are
consumed! The mice eat almost twice as much as control animals but
because of their hyperactivity, utilize the excess calories to satisfy
their energy demands. Perhaps the new paradigm in aging research
should be that sustained activity extends life span. At this point,
both the extended life span and the prolonged reproductive capacity of
the PEPCK-Cmus mice need detailed study before hard conclusions,
rather than speculation, will be forthcoming."
Excellent !!! This is a mutant mouse construct demonstrating a
perfect adaptation to the laboratory environment with food and refined
calories abundance. If this is replicated in human being we will get
perfect adaptation to the modern life in the city thriving on junk
foods and being overactive with the side benefit of increased
reproduction! These mutants will win in the prosperous western
environment.
But I wonder what happens if this mouse is hit by famine - just put it
in the wild during winter and let's see ...
Taka
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