How Your Muscles Grow

It's a simple, albeit rarely asked question: How do our muscles grow? Really now, have you ever spent any time researching the subject to delineate the hypertrophy process in skeletal muscle tissue? I bet you haven't.

Why? Because we normally limit our "research" to the training parameters and nutritional guidelines that are purported to induce hypertrophy. The lack of specific knowledge of hypertrophy possessed by most trainers and trainees isn't surprising since, up until the last few years, much of the hypertrophy process was ambiguous.

Why Do We Lift Weights?

Most of us lift weights to build bigger muscles. Sure, many of us also seek über-strength; however, if given the choice, I bet the majority of T-Nation readers would favor big muscles over big lifts.

Therefore, this information is intended to help you better understand how your muscles grow bigger. And somewhere along the way, you'll probably develop a clearer picture of why we train with certain levels of intensity and volume. Moreover, you might begin to question your current parameters in favor of more novel methods. (Yep, my high frequency training views just might coalesce with this information.)

Resistance training causes muscle damage if the volume and intensity relationship is sufficient. By performing an exercise such as the back squat for quadriceps hypertrophy, you're creating microscopic damage to your quadriceps fibers that send a signal for growth and repair.

Importantly, "growth" and "repair" both refer to the hypertrophy process. Indeed, the repair of damaged muscle is what causes the growth. But specifically, what is this "repair" process I'm referring to?

Stem Cells and Politics

I'm sure you're familiar with the ongoing ethical and political debates regarding stem cells. While this article is certainly not a lesson in ethics, it's pretty clear that stem cell research could revolutionize our world with regard to tissue regeneration, and it could lead to novel treatments for various diseases. Let's review the role of stem cells.

Stem cells are general, non-specific (undifferentiated) cells that can transform into any cell in the body. Liver, skin, retina, muscle - they're all possible cell types that can be created by stem cells. When muscle fibers are damaged from resistance training, stem cells accumulate at the site of damage to induce muscle fiber growth.

These stem cells are named satellite cells in skeletal muscle tissue for no reason other than to confuse you (okay, not really). That muscle growth you've experienced since discovering T-Nation? Yep, you can thank your satellite cells since they caused the formation of new actin and myosin proteins at the site of damage. How'd they do this, you ask?

Following a bout of stressful resistance training, your muscles are damaged. This damage must be repaired. So, your muscles must send a signal to the satellite cells so the repair process can occur.

This is akin to your buddy who's getting his "clock cleaned" at the local watering hole. If it weren't for his girlfriend's 2 A.M. call to tell you that he overstayed his welcome at the beer joint, you'd never know he was in dire straits. Recent research demonstrates that mechano growth factor (MGF) is what "calls" your satellite cells to repair the damage after exercise (1). MGF is derived from the insulin-like growth factor (IGF-1).

In response to growth hormone, the IGF-1 gene can splice to form a gene known as IGF-1Ea. It's been postulated that the IGF-1Ea gene might be first expressed in response to exercise-induced muscle damage. However, Adams demonstrated that MGF is expressed earlier than IGF-1Ea after exercise (2).

Therefore, MGF appears to be the first party called to clean up the mess. Importantly, the expression of MGF after exercise-induced damage lasts for only a day or so (3), followed by IGF-1Ea expression that lasts for much longer.

After resistance training muscle damage, the human IGF-1 gene can be spliced to produce IGF-1Ea and MGF. Hormones (e.g. growth hormone) cause the upregulation of IGF-1Ea. It appears that local muscle cell damage (mechanical overload) is what might cause the IGF-1 gene to upregulate expression of MGF.

In other words, both IGF-1Ea and MGF are upregulated after exercise; however, each is created in response to a different signal - the two signals being hormonal (IGF-1Ea) and mechanical (MGF).

Furthermore, in response to exercise, MGF appears to upregulate before IGF-1Ea, and MGF is shorter lived (~24 hours). Mechanical overload (i.e. muscle damage) sends a signal to the regulatory sequence 1 portion of the human IGF-1 gene; hormones send a signal to the regulatory sequence 2 of the same gene. Each of these signals cause increased expression of MGF and IGF-1Ea, respectively.

		IGF-1Ea Expression Hormones
Reg Seq 1	1	Reg Seq 2	2	3	4	5	6
	Human IGF-1 Gene
Muscle Damage MGF Expression

Too much science for ya? Okay, I'll summarize what I've mentioned thus far. Importantly, the following sequence shows the time order of events that research demonstrates. It does not indicate that one process is necessarily dependent on the other.

What's Been Demonstrated (For Now)

Exercise-Induced Muscle Damage

MGF Expression
(due to mechanical overload)

IGF-1Ea Expression
(due to hormonal signals)

Satellite Cell Accumulation

Muscle Growth

Is MGF the Answer to Your Hypertrophy Woes?

Obviously, MGF has created much discussion amongst the scientific community. Importantly, both IGF-1Ea and MGF can induce skeletal muscle hypertrophy. But the question remains: which appears to be a more powerful trigger for hypertrophy?

Two similar experiments were performed that helped shed some light on the answer. Musaro injected IGF-1Ea cDNA into rat muscles. Goldspink injected MGF cDNA into mouse muscles. In Musaro's study, a 25% increase in fiber cross-sectional was observed after four months (4). Goldspink demonstrated a 25% increase in the fiber cross-sectional area within two weeks!

Exciting? Well, Carl Sagan once said, "Extraordinary claims require extraordinary evidence." Unfortunately, I can't look at Goldspink's study with a critical eye since very little information is available on the technique he used. Indeed, Goldspink is holding that information very tightly. Sagan wouldn't be pleased.

Nevertheless, a few other studies have pointed toward the potential hypertrophic effects that MGF might induce. We all know that muscle mass declines with aging. Could MGF be the reason for this decline?

Owino et al demonstrated that the muscles of older rats expressed significantly lower levels of MGF compared to younger rats (5). Hameed et al reported a similar finding in the muscles of humans (6). However, it's known that growth hormone declines with aging. Therefore, since growth hormone declines, IGF-1 likely declines with it since growth hormone upregulates the IGF-1 gene.

As such, less MGF would be expressed if the expression of IGF-1 decreased. In other words, the demonstration that MGF is lower in elderly muscles might simply be due to a decline in growth hormone.

The Future of Hypertrophy Training?

Here's what we know. The formation of new muscle tissue requires the donation of a nucleus. So, if you want to grow more muscle tissue, you must have satellite cell accumulation at the site of damage since satellite cells donate a nucleus that allows for muscle fiber formation.

Therefore, for super-fast hypertrophy, it appears that you must upregulate one, or many, of the steps within the hypertrophy cascade that induce satellite cell accumulation.

It doesn't appear that IGF-1Ea is the answer. After all, Musaro's demonstration of a 25% increase in cross-sectional area isn't very profound since the process took four months. That's not to say that any of us wouldn't appreciate such size gains; however, expression of MGF appears to be much more powerful.

What's interesting about MGF expression is that it's all but diminished after ~24 hours. Could this be reason enough to train your muscles every 24 hours? It seems if we could upregulate MGF expression every 24 hours without overloading the system, we might be able to shift the anabolic:catabolic ratio in our favor. So, the idea is to upregulate MGF expression with resistance training, and to keep the process going at the highest level possible.

What if we trained our muscles every 12 hours? After all, if MGF upregulation does induce satellite cell proliferation at the site of damage, could each resistance training session cause an upregulation of MGF expression, thus leading to more muscle? In other words, would further stimulation at the 12 hour mark increase MGF expression, or would it create a negative feedback, thus diminishing expression?

Would 12 hours be enough time to allow MGF to do its "magic" before we upregulated it again? Could MGF be upregulated again within 24 hours, or must we wait until it diminishes before reactivation? Unfortunately, at this point, no one knows. However, if any of these are true, then high frequency workout regimens just might be the future of hypertrophy training.

The Boot Camp Effect?

Now, I must back up a little because I'm going out on a limb. There's enough ambiguity within the hypertrophy process to fill Bill Gate's wallet. Obviously, I haven't mentioned the issue of nutrition and the real-world examples of overtraining in lifters who've annihilated their muscles with daily training sessions. Indeed, without proper rest and nutrition, you can be sure the likelihood of MGF causing hypertrophy would decrease.

Furthermore, it's likely that there are other unknown processes that cause the hypertrophy response. I'm trying to coalesce the muscle growth examples I've seen in the real world with what science is currently demonstrating with regard to the hypertrophy response. The most substantial, and fastest, hypertrophy increases I've ever witnessed were with individuals who trained their muscles with very high frequencies.

I'll never forget how shocked I was when my buddy returned from boot camp. Not only had he lost 20 pounds of fat, but he drastically increased the size of his pecs. I asked him what in the hell he'd done for his pecs? He shrugged his shoulders and said, "All I know is that I was told to do 20 push-ups about every 90 minutes."

Could this hypertrophy be due to an upregulation of MGF, IGF-1Ea, or a combination of the two? Based on the aforementioned research, it appears that MGF might be the most powerful factor.

Two things seem evident. First, a surplus of calories each day will make hypertrophy much easier on a high frequency plan. Second, daily training sessions with excessive volume and intensity would likely shift the anabolic:catabolic ratio far enough out of whack to offset any noticeable hypertrophy.

Therefore, it seems that a well-designed high frequency plan would include constantly changing parameters in order to manage fatigue and control the catabolic effects of constant stimulation.

Conclusion

I've given you a little insight into my brainstorming that created the Perfect 10 training program. If you've been appalled by the underdevelopment of any body part, I suggest you give it a try. The feedback I've received has been incredible.

Here's what the future holds. I've taken the info in this article a step further, and I've compiled much feedback from trainees all over the world who've been on my Perfect 10 program. In the near future, I'm going to release a program that should turn this industry upside down. Stay tuned!

References

1. McKoy G, et al. (1999) J Physiol 516: 583-592.

2. Adams GR (2002) J Appl Physiol 93: 1159-1167.

3. Hill M & Goldspink G. (2003) J Physiol 549: 409-418.

4. Musaro A, et al. (2001) Nat Genet 27: 195-200.

5. Owino V, et al. (2001) FEBS Lett 506: 259-263.

6. Hameed M, et al. (2003) J Physiol 547: 247-254.