February 1, 1999
Volume 2, Number 3
Research Update
by Bryan Haycock MSc., CSCS
bryan@thinkmuscle.com
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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! IGF-1 once again proves to be one
of the most powerful mediators of muscle growth.
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.
by Bryan Haycock MSc., CSCS
bryan@thinkmuscle.com
Please send us your feedback
on this article.
