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Old 09-06-2007, 12:45 AM
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Default Genetics and Muscle Growth - What are the factors?

My Major professor, Dr. Kim and I are currently working on some extensive and exciting research on skeletal muscle tissue. I wanted to share some research from Kim on what at least partly may explain genetic differences between individuals. The study is

Bamman MM, Petrella JK, Kim JS, Mayhew DL, Cross JM.Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humans. J Appl Physiol. 2007 Jun;102(6):2232-9. Epub 2007 Mar 29.

First, let me give you some background.

Concept 1. The myonuclear domain theory

Muscle fibers have several nuclei (are multinucleated).
As you know the nucleus contains the genetic information specific for building the proteins in the muscle cell.

The myonuclear domain theory suggests that each nucleus is responsible for a certain region of the muscle fiber, and that the region it controls is limited.

This means that theoretically if we resistance train, muscle fibers can expand but only to a point which can be handled by the existing nuclei. After this the muscle fiber must add new nuclei or further growth cannot occur.

When growth occurs this is known as 'expansion of the myonuclear domain'

Sattelite cells - On the muscle cell you have specific cells which like our moon are located to the periphery of the muscle fiber between the outside layer just before the muscle fiber known as the basal lamina, and the actual cell membrane of the muscle fiber known as the sarcolema.

Basically, evidence is clear that after resistance training these cells begin to divide, and then they travel to the injured site of the cell. Here they actually stimulate the regeneration of the muscle fiber, and they also differentiate or change into myotubes which are immature muscle fibers. These myotubes contain the contractile proteins myosin and actin, and finally the myotubes end out fusing to the muscle fiber. In the process they donate new contractile proteins making the fiber bigger and
they donate their nuclei!

Well. Kim and colleagues have found in past studies that young males have 2 times more growth then the elderly and young females and that the difference between the two is that the young males are the only group to actually add new nuclei to their muscle cells. While the elderly and females also grow, they did not increase cell nuclei. So what happened is that they ended out hitting a growth ceiling as discussed earlier.
Using advanced statistics they found that muscle fibers could not expand beyond 2,000 Ám2 before needing the addition of new nuclei.

Here is that study

Petrella JK, Kim JS, Cross JM, Kosek DJ, Bamman MM.Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E937-46.

Now that you have a background, lets talk about the study of interest

Bamman MM, Petrella JK, Kim JS, Mayhew DL, Cross JM.Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humans. J Appl Physiol. 2007 Jun;102(6):2232-9. Epub 2007 Mar 29.

66 people who fell in young and elderly age groups. Subjects underwent 16 wk of resistance training (3 days/wk) focused primarily on the knee extensors.

After the 16 weeks they divided individuals up into 3 clusters

1. Extreme responders (gained a lot of muscle)
2. moderate responders
3. non responders ( no significant increase in muscle)

The three responder clusters did not differ by training intensity, training volume, or adherence to the program.

Growth Factors which regulate sattelite cell activation

There are a number of growth factors which stimulate sattelite cells to both divide and differentiate (to change into immature muscle cells and fuse to existing ones).

Two you should be aware of are

1. Insulin like growth factor I - There is a form which is released locally in muscle tissue known as mechanogrowth factor. This is known to to activate sattelite cells to proliferate, and possibly to also differentiate (though another form of IGF in muscle may assist in the latter process more)

2. Myogenin - this is a transcription factor, or a protein which stimulates sattelite cells to differentiate.

They found essentially that mechanogrowth factor, and myogenin were higher in the extreme responders, moderate in the moderate responders and low in the non responders.


Well, I can go much deeper than this, but let me explain things as follows

1. Sattelite cells even in non responders or aged muscle appear to be able to be activated as good as responders

2. what is different is the surrounding suit of growth factors.
Thus, genetic differences in growth may be related to satellite cells, and in particular the growth factors in one individual relative to another.

3. This study looked elderly as well as young men. And whats cool is that they actually found that some of the extreme responders were in the aged group! This means that while overall the average of elderly men is lower than young, that there are those with the capacity for extreme growth. Also they found non responders in young individuals, which means that there are young individuals who do not release enough growth factors for substantial satellite cell activation and therefore growth.

What can we do about this, E.G. are there any practical applications?

Well, there may very well be. What Dr. Kim and I are looking into is ways to enhance signal transduction through nutritional supplementation. One thought is that mechanical signals ultimately trigger growth factors, and this all occurs through the cell membrane. What we know is that the integrity of the cell membrane is critical to conduct these signals. Therefore certain supplements which strengthen the integrity of the cell membrane would theoretically enhance signal transduction. This will actually be what my Dissertation will be on.
Dr. Jacob Wilson, Ph.D, CSCS
Professor of Exercise Science, University of Tampa Bay

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