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IGF-1 the Most Powerful Mediators of Muscle Growth
As we approach the new millennium we find the science of building muscle
progressing faster than ever before. Long gone are the days of simple trial and
error when it comes to building muscle. The modern bodybuilder demands more than
just "hear say" if they are to adopt a new training routine or nutritional
supplement. This column was created to keep today�s bodybuilder on the cutting
edge of scientific research that might benefit them in their quest for body
perfection.
Not since the travels of Juan Ponce de Leon has the fountain of youth seemed so
close!
Title:
Viral mediated expression of insulin-like growth factor I blocks the
aging-related loss of skeletal muscle function
Researchers:
Elisabeth R. Barton-Davis*, Daria I. Shoturma*, Antonio Musaro, Nadia Rosenthal,
and H. Lee Sweeney*,
* Department of Physiology, University of Pennsylvania School of Medicine,
Philadelphia, PA and Cardiovascular Research Center, Massachusetts General
Hospital, Charlestown, MA
Source:
Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15603-7
Summary:
Although the mechanisms underlying age associated muscle loss are not entirely
understood, researchers attempted to moderate the loss by increasing the
regenerative capacity of muscle. This involved the injection of a recombinant
adeno-associated virus directing overexpression of insulin-like growth factor I
(IGF-I) in differentiated muscle fibers.
They demonstrated that the IGF-I expression promotes an average increase of 15%
in muscle mass and a 14% increase in strength in young adult mice (Figure 1),
and remarkably, prevents aging-related muscle changes in old adult mice,
resulting in a 27% increase in strength as compared with uninjected old muscles
(Figure 2). Muscle mass and fiber type distributions were maintained at levels
similar to those in young adults. These results suggest that gene transfer of
IGF-I into muscle could form the basis of a human gene therapy for preventing
the loss of muscle function associated with aging and may be of benefit in
diseases where the rate of damage to skeletal muscle is accelerated.
Discussion:
I�m not sure where to begin. This study has the potential to completely change
the way we age.
In this experiment, a recombinant adeno-associated virus, directing
overexpression of insulin-like growth factor I (IGF-I) in mature muscle fibers,
was injected into the muscles of mice. The DNA that was originally in the virus
was removed along with markers that stimulate immune response. DNA coding for
IGF-1 was then put into the virus along with a promoter gene to ensure high
rates of transcription. The results, as you can see by figures 1 & 2, were
dramatic.
IGF-1 plays a crucial role in muscle regeneration. IGF-1 stimulates both
proliferation and differentiation of stem cells in an autocrine-paracrine
manner, although it induces differentiation to a much greater degree. IGF-1,
when injected locally, increases satellite cell activity, muscle DNA, muscle
protein content, muscle weight and muscle cross sectional area. The importance
of IGF-1 lies in the fact that all of its apparent functions act to induce
muscle growth with or without overload although it really shines as a growth
promoter when combined with physical loading of the muscle.
IGF-1 also acts as an endocrine growth factor having an anabolic effect on
distant tissues once released into the blood stream by the liver. IGF-1
possesses the insulin-like property of inhibiting degradation, but in addition
can stimulate protein synthesis. The insulin-like effects are probably due to
the similarity of the signaling pathways between insulin and IGF-1 following
ligand binding at the receptors.
The ability of IGF-I to stimulate protein synthesis resembles the action of GH,
which was shown in separate studies on volunteers to stimulate protein synthesis
without affecting protein degradation. Although it is often believed that the
effects of GH are mediated through IGF-1, this cannot be the case entirely.
First, the effects of the two hormones are different, in that GH does not change
protein degradation. Second, the effect of GH is observed with little or no
change in systemic IGF-1 concentrations. Age related muscle loss has been
prevented with GH injections, however it is believed that this is accomplished
through IGF-1.
The results of this study are similar to other studies where IGF-1 was injected
directly into muscle tissue, resulting in increases in size and strength of
experimental animals. Using a virus as a genetic vehicle has an advantage over
simply injecting the growth factor. The effects of a single viral treatment last
significantly longer (months if not years) because the muscle cell itself is
constantly overproducing its own IGF-1 from injected DNA.
The fact that the IGF-1 produced by the muscle of these mice did not reach the
blood stream is interesting. Systemic injections of IGF-1 have not been
successful in inducing this kind of anabolic effect in humans. In addition,
IGF-1 produced by the liver is genetically different than that produced by
muscle tissue. It could be that providing additional DNA for the muscle to
produce it�s own IGF-1 is the key to achieving anabolic and rejuvenative effects
specifically in skeletal muscle.
In this study there was a preferential preservation of type IIb muscle fibers in
aging mice. These are the fibers most sensitive to muscle hypertrophy from
training and they are also the first fibers to disappear with aging. In the mice
receiving the engineered virus, there was also a preservation of the motor
neuron, leading to an increase in functional capacity. It is speculated that age
related muscle loss is secondary to the loss of neuronal activation of type-II
fibers. By preventing the degeneration of typ-II motor units, functional
capacity could be maintained into old age. This technique may also serve useful
in the prevention of osteoporosis. Further study is necessary to determine
wether IGF-1 is having an effect only on muscle fibers or on nervous tissues as
well.
Finally, it was also exciting to see muscle growth in the young mice who
received the injection (15% increase in muscle mass). This means that the
injection provided levels of IGF-1 far and above what the muscle normally has
access to and not simply a preservation of normal levels. Remember that this was
not combined with exercise. The growth of the injected muscles happened even
without an extreme mechanical stimulus. The mice were simply allowed to run
around as they usually do. Because of these dramatic results, the authors
expressed concern about the use of this technique to enhance performance or
cosmetic appearance. Research Update is not my personal soap box so I won�t go
off on the gender centered hypocrisy of cosmetic enhancement in our society. All
we can hope for is that this technique will be used to treat more important
diseases such as muscular dystrophy and thereby become somewhat available for
other uses as well.
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