Pulled this from another board, lengthy but very good read.

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 ADVANCE \d4 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 its 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 whether 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 soapbox 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.




IGF1, also known as somatomedin C, is polypeptide hormone about the same size as insulin. It is produced predominantly in the liver in response to growth hormone (GH) release from the pituitary gland. Many of the growth promoting effects of GH are due to its ability to release IGF1 from the liver. The conversion ratio of GH to IGF1 varies greatly in different individuals but most external sources of GH convert around 4-6mcg of IGF per one I.U. of GH. IGF-1 acts on several different tissues to enhance growth. IGF1 belongs in the 'superfamily' of substances known as 'growth factors,' along with epidermal (skin), transforming; platelet derived fibroblast, nerve, and ciliary neurotrophic growth factors. None of the other factors have any bearing on exoskeletal tissue incidentally however These agents all have in common the ability to stimulate cell division, known as mitogenesis, and cell differentiation. Meaning That In the case of IGF1 which does act on muscle tissue it will initiate the growth of new muscle fibers, and subsequently new receptors for testosterone. Users have unanimously concluded that it enhances cycles of steroids significantly. They also seem to be adamant about its ability to reduce fat and improve vascularity a great deal.



The IGF1 Hype



There is a considerable amount of hype surrounding IGF1. Every one is blaming the distended bellies of modern Bodybuilders on it. Also the freaky proportions that old bodybuilders that have been around for years are starting to attain. Anti-aging proponents are touting it as the miracle cure for every thing from Parkinson's disease to Alzheimer's. And the medical community has published numerous articles on it for its ability to cause cancer, diabetes and gigantism. While at the same time performing documented experiments on thousands of patients of muscle wasting diseases. And reporting significant turnabouts in there conditions. So what is a guy to think about IGF1 as far as athletic enhancement is concerned? Well first of all you need to know that most experiments conducted with IGF1 do not list the type of IGF used. I have written Dr. Robert Saline of the Swedish rejuvenation institute on several occasions and we have had in-depth discussions on the subject of IGF1 for physical appearance enhancement. He feels it would be unethical to prescribe IGF1 to a bodybuilder to increase muscle mass simply due to the fact that IGF1 has valid applications in the medical community, (Like I could give a rats ass about "ethical"). He can not argue that it is extremely effective as a promoter of muscle growth far beyond what androgens (steroids) alone can offer. Well fortunately in America IGF1 is not a drug (yet) and the FDA has no control over it as of now. This will change in the very near future however, Im absolutely sure of it.



How to use IGF1



Assuming that you have acquired legitimate IGF1 (R3) long chain, That's IGF1 with the binding protein added. You should take dosages ranging from 60mcg up to 120mcg per day in divided doses. One injection in the morning and again at bed time. Never exceed 120mcg in one day. IGF1 can cause serious gastrointestinal problems such as tumors intestinal swelling diarrhea and vomiting. Most IGF1 comes in a concentration of 1000mcg per ML or CC so it makes it easy to measure in an insulin syringe. 10 IU on the syringe is 100mcg. Do the math.



IGF + Insulin



If you plan on doing IGF1 with Insulin, listen closely IGF1 is not that expensive, sure you can get away with using less by including insulin in the stack, but IGF1 and Insulin together have a pro-insulin effect on your blood sugar balance. It can enhance the chances of a hypoglycemic episode ten fold. I would recommend against it for any one not ABSOLUTLY comfortable with insulin or IGF1.



Here is how insulin and IGF1 work together. Igfbp3 is the binding protein, which allows IGF1 to remain active in the system for a long enough period of time to really work its magic. IGF1 by nature has a half-life of less than 10 minutes by its self. The molecule was so small it would escape the blood stream very rapidly. This was the reason IGF1 was so "underground". It took very frequent injections at high dosages to achieve even minimal results. Aside from this reconstituting the compound required a degree in biochemistry. This short acting version was the only IGF1 known until recently IGF1 would have been administered in 100 mcg dosages 4-6 times a day. That is a hell of a lot of IGF1. That explains a lot of the distended bellies. Now with R3 long chain IGF1 and the Binding protein IGFBP3 IGF1 will last up to 6 hours in the system. By binding IGF to the IGFBP3 you make the molecule larger and it gets trapped in the blood stream until the protein is broken down and the IGF molecule escapes. You can further its life by combining Insulin with it, although I here its very risky. Insulin prevents the breakdown of IGFBP3 and leaves the IGF1 molecule roaming free in the blood stream for longer periods of time up to 12 hours as insulin levels return to normal IGFBP3 will begin to break down and the IGF1 will escape from its bound protein IGFBP3 again having a half life of less than 10 minutes.



Insulin should be taken at the normal dosage it is usually administered at minus 10% about 45 minutes prior to the IGF1 infusion. Again let me remind you this can be deadly if you don't know what you are doing. And of course do not use Insulin for the nighttime injection of IGF1 by taking it in the morning you prolong the IGF1's half life to 12 hours and then take a 6 hour injection, you should be fine. Hell if you want to eat a big bowl of rice and drink another 100g of simple carbs 45 minutes before the bed time IGF1 infusion you could spike insulin for at least a few hours of extended IGF1 activity. If your not going to be using insulin in the stack then go ahead and do the same in the morning.



What users report



Users of IGF1 have reported various results but all along the same lines, It does not appear to be dramatically less effective in any one individual (at least not to the best of my knowledge). I have a good friend who had to stop taking IGF1 due to stomach illness that was completely unrelated But he to experienced good gains from it for the 2 weeks he was on it, his dosage was 120mcg per day. One hour after the first injection he went to the gym and immediately told me about the uncontrollable pump he got from just one set.



That would indicate to me that he was experiencing some form of cell volumization. The general consensus on IGF1 seems to be that its benefits are as fallow:



Increased Pump Pumps are reported to be so severe that workouts are often cut short due to lack of ability to the muscle through the full range of motion...ouch



Gains retention is increased if IGF is used in a cycle I am not sure why, but IGF1 seems to make gains on a cycle stick with virtually no post cycle loss. Every bodybuilder I've spoken with seems to think this for some reason. Most of them use drugs like Anadrol or Dianabol with it because of the amount of size attained with these drugs. The usual draw back to these drugs is that in most users there is a post cycle "crash" that occurs, so the reasoning is to toss IGF1 into the stack and grow larger faster with out the post cycle crash blues.



Reverses testicular atrophy



Testicles if shrunken will return to "full swing" so to speak even in the middle of a cycle. If not shrunken they will not shrink during the cycle. This may explain partially why gains are kept after the cycle.



Fatigue



Users report feeling drained and tired all day. This seems to be one of the negative side effects to IGF1, it will make you sleep longer and you will require more sleep at night to feel rested for the morning. This is common with high doses of HGH and exhibited in children, whose IGF1 levels are extraordinarily high. A child needs 4 hours more sleep than an adult on average does. This may be directly or indirectly related to IGF1 levels.



Stiffness



An almost arthritic feeling is commonly associated with high levels of HGH, well IGF1 has the exact same property. IGF1 will cause your hands, fingers and knuckles to ache this is one way you can be sure you got real IGF1.



IGF-1's Side effects



Every thing has a down side. To bake a cake ya gotta brake an egg. IGF1 is no exception. The drug used in larger quantity around the 100mcg+ range will cause headaches, occasional nausea and can contribute to low blood sugar or hypoglycemia in some users. Although I have never heard of this first hand I'm sure its true.



IGF1 will attach its self to the lining of the intestine and cause atrophy of the gut. Every thing IGF1 touches will grow and you have a lot of receptors on the lining of the large intestine and inner wall of the abdominal well. This is what causes the GH gut look. You can easily avoid this by limiting your dosages and cycle lengths. IGF1 cycles should be kept to 4-6 weeks with 4-6 weeks off in-between. IGF-1 is considerably more powerful than HGH and you need to think of it along those lines as far as dosing goes. We all know what to much HGH can do over prolonged periods of usage. The Neanderthal look is definitely not going to win any shows this year. I would recommend 80 mcg a day for 4 weeks at a time you should get good results from that for a while. I don't know if you will need to up the dosage at any point, but I would think in the case of IGF1 it wouldn't matter. If 80mcg doesn't do it for ya, then bump it up to 100 You should definitely feel it at this point If not suspect the IGF1 as being fake. Beyond 120 mcg per day your asking for trouble, This compound demands as much respect as its sister amino Insulin.



Clinical Facts about IGF-1



IGF-1 is a polypeptide of 70 amino acids (7650 daltons), and is one of a number of related insulin-like growth factors present in the circulation. The molecule shows approximately 50% sequence homology with proinsulin and has a number of biological activities similar to insulin. IGF-1 is a mediator of longitudinal growth in humans or how tall you are capable of becoming. Serum IGF-1 concentrations are altered by age, nutritional status, body composition, and growth hormone secretion. A single basal IGF-1 level is useful in the assessment of short stature in children and in nutritional support studies of acutely ill patients. For the diagnosis of acromegaly, a single IGF-1 concentration is more reliable than a random hGH measurement (Oppizi, et al., 1986). IGF-1 can be used for the assessment of disease activity in acromegaly (Barkan, et al., 198.



Almost all (>95%) of serum IGF-1 circulates bound to specific IGF binding proteins (IGFBPs), of which six classes (IGFBPs 1-6) have been identified (Rudd, 1991). BP3 is thought to be the major binding protein of IGF-1.