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Willyumyum
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Alright I just took about 10 minutes and typed this as fast as I could... I thought it would be an interesting read for everyone, and something different to discuss..
MYOSTATIN BLOCKERS - Anabolic super-drugs of the future?
by Carlon M. Colker, MD, FACN...
If you are a true hard-core iron pumping junkie like I am, get ready to be completely freaked out by what I am about to tell you.. And I'm not talking about just being a little weirded out by the info that follows. I'm talking about a real mind-bender of literally gargantuan proportions.
What would you say if I told you it is quite possible that you could gain 100 pounds of muscle without ever having to pick up a weight?
On the one hand, for most upstart meatheads, the very concept will excite you. On the other hand, what a major bummer for those who have slaved away for years in the gym and struggled to make gains! Think of all the time and effort you might have put into the gym. Think about the sweat and tears. Maybe you don't have nearly 25 years of bodybuilding behind you like I do to pull your hair out over, but if you've put in at least a few years of religious commitment to what I call "the iron altar," you can at least somewhat relate to what I'm saying. Of course, either way you look at it , for the iron-blooded set, the very concept of a substance being able to cause virtually instant massive muscle growth is seductive beyond belief.
In simple terms, here is the scoop: recent published research has elucidated the true secret to muscle growth. Do you feel as if you've been killing yourself every day in the gym with little to show for it? Have you then compared yourself to the muscle head next to you who comes in only on weekend to do a lazy routine, but somehow still looks gigantic. Yes, it sucks. But this seemingly unfair difference seems to be largely the result of one substance - myostatin
NO HAPPY WHEEL NEEDED
About five years ago, the presence of myostatin (then called "growth and differentiation factor 8" or "GDF-8") was identified to be responsible for actually inhibiting the growth of muscle tissue in animals. To be precise, it was found that mice lacking the gene needed to produce myostatin actually gained slabs of beef without any resistance or exercise! Basically, these little buggers just laid around in their cages and got hugely muscled without even getting off their fuzzy little butts and getting on their happy wheel (or whatever it is they do for exercise).
In layman's terms, myostatin is basically a protein composed of a sequence of amino acids. It's produced by a specific gene sequence in the DNA of nearly every vertebrate-containing animal from the brook trout to the animal you wake up to every morning in the bathroom mirror. Myostatin works in the embryonic phase and during development to inhibit the growth of muscle. The "reason" for such a substance probably has something to do with an innate need to control and regulate the production of excess muscle.
Perhaps, from an evolutionary standpoint, having too much muscular bulk was actually a survival disadvantage. Maybe having too much mass meant not being able to get away quickly enough from danger. I imagine some buff and beefy ancestor cave dwellers spent too much time tanning their massive bodies in the sun and preening their animal-skin banana hammocks, only to end up food for a tyrannosaura (whatever -- sorry, a dinosaur expert I'm not). Of course, for the more religious set, perhaps the good Lord just doesn't care for big-muscled dudes, and that's why we have myostatin.
But, all kidding aside, for whatever reason we can theorize, the fact is that evolution has definitely selected out the myostatin-null population (i.e., those missing the gene sequence) and minimized their occurrence. OF course, if you are looking for a real ("real big," that is) example of the influence of the myostatin gene and how missing it causes colossal changes in appearance, you need to look no further than the good old cattle population. It turns out we see the proof of the muscle growth inhibiting power of myostatin in the rare but heritable condition among specific sub-population of cattle.
The Belgian Blue and the Piedmontese breeds are born with mutations in the sequence of their DNA that "codes" (i.e., produces) myostatin.² The result of their lack of myostatin is, to put it bluntly, a lot of bull! These animals are so big that it's beyond the ridiculous. In fact, one slow lumbering clip-clop over to the food trough, and their muscles ripple with a pump. Sometimes their rumps get so big from the lack of myostatin, that folds of muscle start hanging on top of each other. But that's muscle, not fat! Of these, the bigger bulls are truly a site to behold, so much so that my words cannot fairly describe how your jaw will drop if you ever get a chance to see on of the real big ones at a county fair, or some such place.
HEALING MATTERS
Although the proof of the effect of myostatin is clear enough in the skeletal muscle of the embryo developing into a mature animal like that of the bullish freaks I mentioned, the effect of myostatin in the adult human is far less understood. We do know that myostatin is secreted as a negative regulator of muscle growth when certain diseases occur in the adult population. For example, serum concentrations of myostatin are elevated in certain HIV+ patients. As a result, when full blown AIDS develops, the muscles deteriorate and waste away as a result of too much myostatin. In addition, we know that there's a myostatin influence when muscular injury occurs. In other words, when muscles are injured from trauma, they need to heal. Just like a cut in the skin forms a scab and eventually heals, injured muscle needs to repair itself. The role of myostatin is to control the healing process and keep it in check.
When skeletal muscles are injured (or after a hard workout), healing cells called "satellite cells" are activated and incorporated into the muscle cells along with various amino acids to promote repair and growth. IF this process occurs in an uncontrolled way, improper and excessive healing might result. Consequently, it's believed that myostatin is locally released to prevent overzealous healing of the muscle and control the rate of repair. In this way, confluent new muscle is produced, and not just a big hunk of poorly formed tissue. Of course, this is all still somewhat theoretical and has yet to be absolutely confirmed. So, its action in the adult human population is still poorly understood.
But, I guess the effect of myostatin on muscle as akin to the effect of some of the dermal (i.i., skin)-derived growth inhibiting factors that prevent skin scar healing from occurring too fast or in too great a degree. Excess skin he align as a result of too little inhibitory regulation can result in a massively over-developed scar called a "keloid." Keloids are more common among black people, and I have seen countless numbers over the years. Some of them can be quite minor and appear just like a puffy scar, while others can be large, shiny and unsightly. Cutting them out never helps because they tend to just reform. Radiation therapy seems to be the only solid method of treatment for the really bad ones. So, based on this parallel theory, one might conclude that the role of myostatin in the adult human is to keep the healing of muscles in check. But this simply has not been proven.
What we do know is that a recent review article from a research group in New Zealand made an interesting summary conclusion as it pertains to myostatin and its effect in the adult human. They concluded that the detection of myostatin in human muscle, combined with myostatin studies of humans with wasting diseases, plus the role of myostatin in the regulation of muscle regeneration ".... provide strong evidence for the role of myostatin in regulating muscle growth after birth." In summary, and simple terms, this is saying that the evidence clearly points to a definite role of myostatin in the adult human. Precisely what role that would be is still unclear.
STEROIDS OBSOLETE?
Either way, in the final analysis of what we know to date about myostatin, all roads seem to lead to the same profound endpoint question for all muscleheads -- could a drug that blocks the genetic expression of myostatin lead to muscle mass gains in the adult human? I would have to answer that question with a resounding YES, but with some serious caveats.
In theory, a "myostatin blocker" might be the ultimate anabolic agent of the future. Such a drug would most certainly make the currently available testosterone-based anabolic steroids and the best growth hormone look like nothing more than multivitamins! Of course, with genetic engineering and single-gene knockout procedures, I dare say the technology does currently exist to make such a drug. Unfortunately, the consequences of an irreversible alteration in genetic expression are frightening, to say the least.
In conclusion, the truth is that I would not lament too heavily over what you would have otherwise dont with all the time you spent pumping iron. I wouldn't chalk up all that hard work to a waste of time just yet. The fact is, the presence of myostatin protein has been shown to influence vital tissues like that of the heart muscle. This aspect of myostatin having an effect on other tissues of the body and not just skeletal muscle is troubling and will have to be taken into serious account in any future drug development technology. For instance, it might very well be that the irreversible alteration in genetic expression caused by such a myostatin blocker would cause the heart muscle to hypertrophy and grow.
Of course, if you have the chest cavity of an ox to house a 10-pound hear, I guess you'd have nothing to worry about!
references
1. McPherron AC., et al. Regulation of skeletal muscle mass in mice by a new TGF-B superfamily member. Nature. 387:83-90, 1997.
2. Kambadur R., et al. Mutations in myostatin (GDF8) in double-muscled belgian Blue and Piedmontese cattle. Genome Res. 7:910-916, 1997
3. Gonzolez-Cadavid NF,. et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc. Natl. Acad. Sci. USA 95:14938-14943, 1998.
4. Thomas MB., et al. Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J. Biol. Chem. 275:40235-40243, 2000
5. Kirk S., et al. Myostatin regulaton during skeltal muscle regeneration. J. Cell Physdiol 184:356-363, 2000.
6. Sharma M et al. Myostatin in growth and repair. Ererc Sports SciRev 29:4; 155-158, 2001
7 Sharma M., et al Myostatin, a transforming growth factor-B superfamily member, is expressed in hear muscle and is upregulated in cardiomyocytes after infart. J. Cell Physiol. 180:1-9, 1999.
YUM
MYOSTATIN BLOCKERS - Anabolic super-drugs of the future?
by Carlon M. Colker, MD, FACN...
If you are a true hard-core iron pumping junkie like I am, get ready to be completely freaked out by what I am about to tell you.. And I'm not talking about just being a little weirded out by the info that follows. I'm talking about a real mind-bender of literally gargantuan proportions.
What would you say if I told you it is quite possible that you could gain 100 pounds of muscle without ever having to pick up a weight?
On the one hand, for most upstart meatheads, the very concept will excite you. On the other hand, what a major bummer for those who have slaved away for years in the gym and struggled to make gains! Think of all the time and effort you might have put into the gym. Think about the sweat and tears. Maybe you don't have nearly 25 years of bodybuilding behind you like I do to pull your hair out over, but if you've put in at least a few years of religious commitment to what I call "the iron altar," you can at least somewhat relate to what I'm saying. Of course, either way you look at it , for the iron-blooded set, the very concept of a substance being able to cause virtually instant massive muscle growth is seductive beyond belief.
In simple terms, here is the scoop: recent published research has elucidated the true secret to muscle growth. Do you feel as if you've been killing yourself every day in the gym with little to show for it? Have you then compared yourself to the muscle head next to you who comes in only on weekend to do a lazy routine, but somehow still looks gigantic. Yes, it sucks. But this seemingly unfair difference seems to be largely the result of one substance - myostatin
NO HAPPY WHEEL NEEDED
About five years ago, the presence of myostatin (then called "growth and differentiation factor 8" or "GDF-8") was identified to be responsible for actually inhibiting the growth of muscle tissue in animals. To be precise, it was found that mice lacking the gene needed to produce myostatin actually gained slabs of beef without any resistance or exercise! Basically, these little buggers just laid around in their cages and got hugely muscled without even getting off their fuzzy little butts and getting on their happy wheel (or whatever it is they do for exercise).
In layman's terms, myostatin is basically a protein composed of a sequence of amino acids. It's produced by a specific gene sequence in the DNA of nearly every vertebrate-containing animal from the brook trout to the animal you wake up to every morning in the bathroom mirror. Myostatin works in the embryonic phase and during development to inhibit the growth of muscle. The "reason" for such a substance probably has something to do with an innate need to control and regulate the production of excess muscle.
Perhaps, from an evolutionary standpoint, having too much muscular bulk was actually a survival disadvantage. Maybe having too much mass meant not being able to get away quickly enough from danger. I imagine some buff and beefy ancestor cave dwellers spent too much time tanning their massive bodies in the sun and preening their animal-skin banana hammocks, only to end up food for a tyrannosaura (whatever -- sorry, a dinosaur expert I'm not). Of course, for the more religious set, perhaps the good Lord just doesn't care for big-muscled dudes, and that's why we have myostatin.
But, all kidding aside, for whatever reason we can theorize, the fact is that evolution has definitely selected out the myostatin-null population (i.e., those missing the gene sequence) and minimized their occurrence. OF course, if you are looking for a real ("real big," that is) example of the influence of the myostatin gene and how missing it causes colossal changes in appearance, you need to look no further than the good old cattle population. It turns out we see the proof of the muscle growth inhibiting power of myostatin in the rare but heritable condition among specific sub-population of cattle.
The Belgian Blue and the Piedmontese breeds are born with mutations in the sequence of their DNA that "codes" (i.e., produces) myostatin.² The result of their lack of myostatin is, to put it bluntly, a lot of bull! These animals are so big that it's beyond the ridiculous. In fact, one slow lumbering clip-clop over to the food trough, and their muscles ripple with a pump. Sometimes their rumps get so big from the lack of myostatin, that folds of muscle start hanging on top of each other. But that's muscle, not fat! Of these, the bigger bulls are truly a site to behold, so much so that my words cannot fairly describe how your jaw will drop if you ever get a chance to see on of the real big ones at a county fair, or some such place.
HEALING MATTERS
Although the proof of the effect of myostatin is clear enough in the skeletal muscle of the embryo developing into a mature animal like that of the bullish freaks I mentioned, the effect of myostatin in the adult human is far less understood. We do know that myostatin is secreted as a negative regulator of muscle growth when certain diseases occur in the adult population. For example, serum concentrations of myostatin are elevated in certain HIV+ patients. As a result, when full blown AIDS develops, the muscles deteriorate and waste away as a result of too much myostatin. In addition, we know that there's a myostatin influence when muscular injury occurs. In other words, when muscles are injured from trauma, they need to heal. Just like a cut in the skin forms a scab and eventually heals, injured muscle needs to repair itself. The role of myostatin is to control the healing process and keep it in check.
When skeletal muscles are injured (or after a hard workout), healing cells called "satellite cells" are activated and incorporated into the muscle cells along with various amino acids to promote repair and growth. IF this process occurs in an uncontrolled way, improper and excessive healing might result. Consequently, it's believed that myostatin is locally released to prevent overzealous healing of the muscle and control the rate of repair. In this way, confluent new muscle is produced, and not just a big hunk of poorly formed tissue. Of course, this is all still somewhat theoretical and has yet to be absolutely confirmed. So, its action in the adult human population is still poorly understood.
But, I guess the effect of myostatin on muscle as akin to the effect of some of the dermal (i.i., skin)-derived growth inhibiting factors that prevent skin scar healing from occurring too fast or in too great a degree. Excess skin he align as a result of too little inhibitory regulation can result in a massively over-developed scar called a "keloid." Keloids are more common among black people, and I have seen countless numbers over the years. Some of them can be quite minor and appear just like a puffy scar, while others can be large, shiny and unsightly. Cutting them out never helps because they tend to just reform. Radiation therapy seems to be the only solid method of treatment for the really bad ones. So, based on this parallel theory, one might conclude that the role of myostatin in the adult human is to keep the healing of muscles in check. But this simply has not been proven.
What we do know is that a recent review article from a research group in New Zealand made an interesting summary conclusion as it pertains to myostatin and its effect in the adult human. They concluded that the detection of myostatin in human muscle, combined with myostatin studies of humans with wasting diseases, plus the role of myostatin in the regulation of muscle regeneration ".... provide strong evidence for the role of myostatin in regulating muscle growth after birth." In summary, and simple terms, this is saying that the evidence clearly points to a definite role of myostatin in the adult human. Precisely what role that would be is still unclear.
STEROIDS OBSOLETE?
Either way, in the final analysis of what we know to date about myostatin, all roads seem to lead to the same profound endpoint question for all muscleheads -- could a drug that blocks the genetic expression of myostatin lead to muscle mass gains in the adult human? I would have to answer that question with a resounding YES, but with some serious caveats.
In theory, a "myostatin blocker" might be the ultimate anabolic agent of the future. Such a drug would most certainly make the currently available testosterone-based anabolic steroids and the best growth hormone look like nothing more than multivitamins! Of course, with genetic engineering and single-gene knockout procedures, I dare say the technology does currently exist to make such a drug. Unfortunately, the consequences of an irreversible alteration in genetic expression are frightening, to say the least.
In conclusion, the truth is that I would not lament too heavily over what you would have otherwise dont with all the time you spent pumping iron. I wouldn't chalk up all that hard work to a waste of time just yet. The fact is, the presence of myostatin protein has been shown to influence vital tissues like that of the heart muscle. This aspect of myostatin having an effect on other tissues of the body and not just skeletal muscle is troubling and will have to be taken into serious account in any future drug development technology. For instance, it might very well be that the irreversible alteration in genetic expression caused by such a myostatin blocker would cause the heart muscle to hypertrophy and grow.
Of course, if you have the chest cavity of an ox to house a 10-pound hear, I guess you'd have nothing to worry about!
references
1. McPherron AC., et al. Regulation of skeletal muscle mass in mice by a new TGF-B superfamily member. Nature. 387:83-90, 1997.
2. Kambadur R., et al. Mutations in myostatin (GDF8) in double-muscled belgian Blue and Piedmontese cattle. Genome Res. 7:910-916, 1997
3. Gonzolez-Cadavid NF,. et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc. Natl. Acad. Sci. USA 95:14938-14943, 1998.
4. Thomas MB., et al. Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J. Biol. Chem. 275:40235-40243, 2000
5. Kirk S., et al. Myostatin regulaton during skeltal muscle regeneration. J. Cell Physdiol 184:356-363, 2000.
6. Sharma M et al. Myostatin in growth and repair. Ererc Sports SciRev 29:4; 155-158, 2001
7 Sharma M., et al Myostatin, a transforming growth factor-B superfamily member, is expressed in hear muscle and is upregulated in cardiomyocytes after infart. J. Cell Physiol. 180:1-9, 1999.
YUM
