Genetics and Muscle Growth - What are the factors? - ABCbodybuilding

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  #1  
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 m2 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.

Conclusions

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.
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Old 09-06-2007, 10:11 AM
MartinofSweden MartinofSweden is offline
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Default Re: Genetics and Muscle Growth - What are the factors?

Thanks for sharing, I find this topic very intersting even though Im not very knowledgeable. Just a few short questions, I hope they make sense: Is there a relationship between the lokal anabolic response from mechanical stimuli and endocrine anabolic hormones, and do the latter in any way influence the magnitude of the former? If there is an adding effect of the two, which would be considered more important for muscle hypertrophy? By the way, if you for some reason would be looking to do a case study on a guy who has an abnormal ability to put on muscle mass and who seems to lack the ability to put on fat let me know.

/ M
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Old 09-07-2007, 12:31 AM
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Default Re: Genetics and Muscle Growth - What are the factors?

Great questions!

[ QUOTE ]
Is there a relationship between the lokal anabolic response from mechanical stimuli and endocrine anabolic hormones, and do the latter in any way influence the magnitude of the former?

[/ QUOTE ]

Local factors will increase powerfully even if endocrine factors are taken out of the equation.
So for example you could have low circulating IGF levels, and still have high local IGF levels. Which is exactly what happens in gymnasts for example. because of their low levels of calories relative to caloric expenditure, they have low circulating IGF, but clearly have great local muscular growth responses. This allows us to adapt to training even under lower calorie conditions

As for part two of the question, yes circulating factors can influence local factors. However the extent of this influence is not well characterized. For example, even though exercise stimulated mechanogrowth factor big time, evidence from studies which have injected GH have found that GH enhanced the amount of MGF in the muscle. So, essentially it seems that you need the mechanical stimulation to activate it, but that systemic factors definately influence this.

In fact one model used in animal studies will transplant an old muscle into a young animals body. Once in the young animals body satellite cell activation acts just as it would have, if they were the original cells of the young animal. This clearly suggests that the surrounding environment also effects the satellite cell response

In addition, in the origional study by kim and colleagues, they found that the young individuals had higher testosterone levels than both elderly males and young females.

[ QUOTE ]
If there is an adding effect of the two, which would be considered more important for muscle hypertrophy? By the way, if you for some reason would be looking to do a case study on a guy who has an abnormal ability to put on muscle mass and who seems to lack the ability to put on fat let me know.

[/ QUOTE ]

Great question! I would suggest from current data that at physiological levels (e.g. your normal hormone levels) that the local effect is the most dominant aspect that drives muscle tissue growth and that systemic or endocrine factors play a larger role in maintaining your overall gains from training. For this reason, people with lower hormone levels may actually need a bit more frequent stimulation to get gains, and definitely to maintain their gains after training.

In terms of their direct effect on muscle growth, I would say that the endocrine factors do play a role at physiological levels in the skeletal muscle adaptation. for example, acute growth hormone responses after exercises are correlated pretty high with muscle growth, suggesting they play a strong role, but not as strong as local factors.

Now, I do not think that the rise in endocrine substances and its effects on growth are completely additive, but may actually augment the local response. As stated earlier, it appears that GH administration, at least in the elderly increases MGF in response to training, so it could augment the local response. So for this question, it is difficult to really come to a solid conclusive answer.

Finally, at supraphysiological levels, such as is used extensively in the IFBB, clearly hormones have a big time effect directly on muscle growth.
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Old 09-07-2007, 05:08 PM
MartinofSweden MartinofSweden is offline
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Default Re: Genetics and Muscle Growth - What are the factors?

President, thanks for the great answers! May I bother you with a few more? First of all let me remind you Im just a layman, and I have not even read the article so forgive me if my questions are irrelevant. One of the things that came up when reading your summay was the way strenght training is defined. I suppose a conventional approach to training for muscle hypertrophy was followed, but I wonder if that is the optimal stimuli for hypertrophy in all individuals (or any, but thats a different qustion), even if the study proved the point that individuals respond differently to this particular type of training.

I suppose heavy multi joint -exercises may result in an increased serum testosterone level, and high intensity strenght training stimulates GH-secretion very well which leads, as you stated above, to an elevated MGF-expression locally, aside from the elevation in growth factors that occurs locally from mechanical stimuli independantly of systemic hormones. From this point of view it would be beneficial to employ heavy resistance, multi joint exercises. If local factors are of more interest on the other hand, then working an individual muscle to full exhaustion (I suppose?) should be the best way to achieve growth, and maybe one should consider training with vascular occlusion. Perhaps a combination of the two would be optimal, stimulating both systemic as well as local factors.

On the other hand, previous research has shown that heavy, high velocity eccentric training induces both strength gain and hypertrophy to a greater extent than both concentric training and conventional strength training. Targeting explosive type fibers was key (and to me still is!). Being a layman Im not sure I understand what mechanisms underlie growth in these different scenarios, or even if there is a difference. For instance, training with vascular occlusion causes practically no injury to myofibrils, while practically nothing causes more damage to them than high velocity eccentric training. In the meanwhile pure concentric contractions, even if under heavy resistance (thereby recruiting type 2X fibers) dont do much for muscle hypertrophy. Taken together it all seem kind of inconclusive, and at times contradictory.

My questions are basically these:

-Are there differnt mechanisms underlying muscular hypertrophy to different types of stimuli?

-Could it be that different people respond differently to different types of stimuli? Perhaps a non-responder to the definition of strenght training above would be a responder to other definitions of strength training?

Thanks for taking your time /M

(By the way, what type of supplements would be beneficial to "wanna be excellent responders"? [img]/forum/images/graemlins/grin.gif[/img])
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Old 09-08-2007, 10:34 AM
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Default Re: Genetics and Muscle Growth - What are the factors?

[ QUOTE ]

-Are there differnt mechanisms underlying muscular hypertrophy to different types of stimuli?



[/ QUOTE ]

First,

great post. You are correct, it is very difficult to define the complete optimal exercise perscription.

One point you made that was fantastic was the use of local, isolation exercises in combination with compound to get growth, particularly for localized growth. In fact, the main way to answer your questions are really to test them in the lab on non responders. E.G. once you have identified a non responder, try and utilize more isolation exercises to bring out a greater localized response.

Now, as to your question of there being different mechanisms, there may be, but ultimately if you are going to get moderate or extreme muscular hypertrophy, no matter what the training stimulus is the end product is going to have to be activation of satellite cells and the subsequent addition of new nuclei to the cell. The evidence is clear on this.

Now as for techniques like blood occlusion, I think one possible mechanism this may work is through a different type of muscle damage, such as oxidative damage. Blood occlusion causes a lot of development of free radicals, and these cause damage to the muscle tissue, which would activate satellite cells. At least that is one possible mechanism.

[ QUOTE ]
-Could it be that different people respond differently to different types of stimuli? Perhaps a non-responder to the definition of strenght training above would be a responder to other definitions of strength training?

[/ QUOTE ]

There is no question about it! Now that we have identified non responders, the next logical step is to examine if there are stimuli which would enhance their growth and bring out moderate to extreme hypertrophy (if this is possible) in them as well.

Here are my thoughts, and this includes you last question as well

1. Ultimately it comes down to activation of satellite cells
2. Satellite cell activation is a matter of transfering mechanical stimuli into a signal which activates satellite cells.
3. Key signals from training occur in the cell membrane of the muscle fiber. So, one possible intervention is to try and maintain the integrity of the cell membrane so that it can signal optimally. For example in the above study they trained 3 days a week hard. But, because the non responders were not releasing
as many local growth factors it may suggest that this type of training is too much stress for them, and instead they should train twice a week each muscle group. Or better yet, they should use a periodized training, alternating heavy load, eccentric concentric training, with less stressful days with less emphasis on eccentric training. By doing so, it allows a continual stimulus, but allows for more time for the cell membrane to maintain enough integrity so that it can signal optimally.

This is just one idea.

There are numerous ideas we need to examine in the lab, and I am definately going to think carefully about all of the things you suggest.

Supplements

Well when we look at mechanical transduction, one of the main signaling molecules is nitric oxide. Mechanical stimuli activates nitric oxide synthase in the muscle cell to produce more N02 and this carries the signal to release local growth factors.

What we know is, in clincial conditions supplementation with Arginine ehances sattelite cell activation. It may be that non responders, may become moderate to extreme responders if we isolate them out in experiments and supplement them with arginine. I'd like to test this in the future.

Now, the most obvious supplement that can ehnance cellular integrity is HMB. In this case, if non responders were supplemented with a high dose of HMB, it may have maintained the integrity of their cell membrane, thereby enhancing mechanical signaling and brought them up to moderate to high hypertrophy.

So, overall I would say non responders may respond differently to both mechanical and nutritiional stimuli!
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Old 09-08-2007, 10:55 AM
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Default Re: Genetics and Muscle Growth - What are the factors?

Once again thanks, your answers are both comprehendable and satisfying.
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Old 09-08-2007, 03:41 PM
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Default Re: Genetics and Muscle Growth - What are the factors?

Thank you as well for your insight as well!
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Old 09-13-2007, 09:53 PM
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Default Re: Genetics and Muscle Growth - What are the factors?

That is very cool Jake! I'm actually doing a paper on the endocrinology of exercise, specifically on testosterone, IGF-1, and growth hormone, so I'll probably include this study and some of your other papers as sources. I haven't started it yet, but when I do I'll probably pm about some topics and thoughts (if that's cool with you). Your dissertation sounds very interesting, when do you plan on finishing it?
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Old 11-21-2012, 01:38 PM
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Default Serum Response Factor

Serum Response Factor seems to be crucial in the adaptation to training, and decreases with age. Check out:
http://www.plosone.org/article/info%...l.pone.0003910
heaps of great references.
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