Muscle Hypertrophy (I wannna get hyooooge)

There has been some very cool studies presented recently in the literature regarding muscle hypertrophy (increase muscle size) and I thought I would take some time to see what new insights we can find to maximize your hard working time in the gym.

Hold on, as here we go!

• Most studies are about 1 year old at best by the time you read them. Presentations are the most updated, as shown by the first abstract below. I went to that session at the ACSM Annual meeting since I was there presenting some other data and it was great! Almost 1.5 years later it comes out in print form.
• The opposite condition from muscle growth (hypertrophy) is atrophy (wasting or getting smaller). If we can really understand muscle atrophy, it will help us figure out hypertrophy.

Tales of Brick Layers and Igloos

Look, Canada!

Two processes occur at the same time

1) Protein Synthesis, adding more protein to muscle tissue.  Think brick layers making a house (or snow blocks making an Igloo if you live in Canada)

2) Protein Degradation (proteolysis), taking more protein from the muscle tissue. Think of your neighbor that you don’t like stealing bricks from your house before they set up (or chipping them off in the middle of the night).  If you live in an Igloo, beware of flames.

Ideally, we want protein synthesis (commonly called an anabolic process) to be increased and protein degradation (commonly called a catabolic process) to be decreased.  End result is more muscle!

In some cases of muscle atrophy, the catabolic processes, are about the same but the anabolic process are reduced.  Some loss of bricks, but almost none being put up (lazy workers), thus resulting in an OVERALL loss of muscle.   The hole in the bucket is bigger than the water coming in. No good!

Fernando et al. found, “After 16 wk of RT, gains in muscle mass, type II
myofiber size, and voluntary strength were similar in young and old”

This is great news, since you can get better if you start training at ANY AGE! Enough with the age excuse!  If I hear one more person state that it is all downhill after age 30 I am going to scream and then chuck a kettlebell at their head.

Bezerra P et al did a cool study where they hooked up 1 leg to electrodes to zap it (youch!) and also had them do a muscle contraction.

• They found a cross educational effect (the LEFT leg got stronger) with just the zapping of the right leg.
• No change in muscle hypertrophy of the LEFT leg, but the right leg got bigger (increased size, CSA).

The nervous system is key for strength and size, but local stress (muscle contraction) is needed for a size increase!

Al Shanti et al stated “Many reviews have focused on understanding the signalling pathways of IGF-I and its receptor, which govern skeletal muscle hypertrophy. However, alternative molecular signalling pathways such as the Ca(2+)/calmodulin-dependent transcriptional pathways should also be considered as potential mediators of muscle growth.“

In English please!

Growth factors IN the muscle (not to be confused with ones just in the blood) like IGF-1 are well known to affect muscle size.

The author argues that other pathways like calmodulin-dependent pathway may be just as important.   There are MANY pathways to muscle size increases with the more popular ones also being the mTOR-1 and probably AMPK too.

Great, But What Can I Do?

• Stimulate the muscle! Go lift something as local stress is probably the biggest factor for muscle hypertrophy.
• Eat something. Increasing insulin may help decrease the protein breakdown process
• Have protein after you train. Protein is required for adding muscle size, so have about 20-30 grams after you are done training.  I prefer CFM whey protein from Protein Factory, but have some protein first and then get nit picky about exactly what type.

Any comments, let me know!

Rock on

Mike T Nelson

REFERENCES

Regulation of Muscle Atrophy: Wasting Away from the Outside In: An Introduction.

Urso ML.

US Army Research Institute of Environmental Medicine, Natick, MA.

Whereas it is clear that periods of detraining, disuse, injury and aging are marked by losses in skeletal muscle mass and function, the emerging literature suggests that there are unique molecular signaling alterations depending on the perturbation. Understanding the phenotypical adaptations in skeletal muscle and factors that are thought to promote or inhibit genes involved in the atrophy program will elucidate how the muscular system responds to decreases in activity. Recent advances in the discipline have identified specific and innovative methods to promote skeletal muscle hypertrophy including gene therapy, pharmacological, and nutritional interventions. The same success has not been met concerning attenuating skeletal muscle atrophy. If novel approaches are to be implemented in humans to mitigate disuse- and age-related skeletal muscle loss, it is imperative that we evaluate critical regulators of skeletal muscle atrophy from a system to the cellular level. The symposium “Regulation of Muscle Atrophy: Wasting Away from the Outside In” was presented at the ACSM Annual Meeting in Indianapolis on May 29, 2008, to provide an overview of the skeletal muscle atrophy literature and our current understanding of the atrophy program from the whole system to the molecular level. In addition, this symposium addressed the feasibility of intervening with specific countermeasures to attenuate atrophy. This introduction identifies the scope of the symposium, which evaluates our current understanding of the atrophy program and how this information can facilitate the development of effective countermeasures.

TRANSLATIONAL
SIGNALING RESPONSES PRECEDING RESISTANCE TRAINING-MEDIATED MYOFIBER
HYPERTROPHY IN YOUNG AND OLD HUMANS.Mayhew DL, Kim JS, Cross JM,
Ferrando AA, Bamman MM.

University of Alabama at Birmingham.

While skeletal muscle protein accretion during resistance training
(RT)-mediated myofiber hypertrophy is thought to result from
up-regulated translation initiation signaling, this concept is based on
responses to a single bout of unaccustomed resistance exercise (RE)
with no measure of hypertrophy across RT. Further, aging appears to
affect acute responses to RE but whether age differences in
responsiveness persist during RT leading to impaired RT adaptation is
unclear. We therefore tested whether muscle protein fractional
synthesis rate (FSR) and Akt/mTOR signaling in response to unaccustomed
RE differed in old vs. young, and whether age differences in acute
responsiveness were associated with differences in muscle hypertrophy
after 16 wk of RT. Fifteen old and 21 young completed the 16 wk study.
The phosphorylation states of Akt, S6K1, RPS6, 4EBP1, eIF4E, and eIF4G
were all elevated (23-199%) 24 h after a bout of unaccustomed RE. A
concomitant 62% increase in FSR was found in a subset (6 old, 8 young).
Age x time interaction was found only for RPS6 phosphorylation (+335%
in old only), while there was an interaction trend (P=0.084) for FSR
(+96% in young only). After 16 wk of RT, gains in muscle mass, type II
myofiber size, and voluntary strength were similar in young and old. In
conclusion, at the level of translational signaling we found no
evidence of impaired responsiveness among old and, for the first time,
we show that changes in translational signaling after unaccustomed RE
were associated with substantial muscle protein accretion (hypertrophy)
during continued RT. Key words: translation initiation, hypertrophy,
muscle fiber, aging.

Effects
of unilateral electromyostimulation superimposed on voluntary training
on strength and cross-sectional area.Bezerra P, Zhou S, Crowley Z,
Brooks L, Hooper A.

Department of Exercise Science, Southern Cross University, P.O. Box 157, Lismore, NSW 2480, Australia. j.bezerra.10@scu.edu.au

In this study we investigate the effects of unilateral voluntary
contraction (VC) and electromyostimulation superimposed on VC (EV)
training on maximal voluntary (MVC) force and cross-sectional area
(CSA), as assessed by magnetic resonance imaging of knee extensors.
Thirty young men were randomly assigned to either a control group (CG),
VC group (VG), or EV group (EVG). The VG and EVG trained the right leg
isometrically three sessions per week for 6 weeks. After training, MVC
increased in the right leg in the VG and in both legs in the EVG, and
EVG was significantly different from CG (all P < 0.01). increased
CSA was found only in the right leg in the VG and EVG (P < 0.01),
and correlated with improvements of MVC (r = 0.49, P = 0.01). It
appeared that the EV training was equally effective as VC at increasing
MVC and CSA, while having a greater cross-education effect. Increased
strength without muscle hypertrophy in the unexercised leg of the EVG
indicated that neural adaptation was responsible for the
cross-education effect.

Ca(2+)/calmodulin-dependent
transcriptional pathways: potential mediators of skeletal muscle growth
and development.Al-Shanti N, Stewart CE.

Institute for Biomedical Research into Human Movement and Health,
Manchester Metropolitan University, John Dalton Building, Oxford Road,
Manchester, M1 5GD, UK.

ABSTRACT The loss of muscle mass with age and disuse has a
significant impact on the physiological and social well-being of the
aged; this is an increasingly important problem as the population
becomes skewed towards older age. Exercise has psychological benefits
but it also impacts on muscle protein synthesis and degradation,
increasing muscle tissue volume in both young and older individuals.
Skeletal muscle hypertrophy involves an increase in muscle mass and
cross-sectional area and associated increased myofibrillar protein
content. Attempts to understand the molecular mechanisms that underlie
muscle growth, development and maintenance, have focused on
characterising the molecular pathways that initiate, maintain and
regenerate skeletal muscle. Such understanding may aid in improving
targeted interventional therapies for age-related muscle loss and
muscle wasting associated with diseases. Two major routes through which
skeletal muscle development and growth are regulated are insulin-like
growth factor I (IGF-I) and Ca(2+)/calmodulin-dependent transcriptional
pathways. Many reviews have focused on understanding the signalling
pathways of IGF-I and its receptor, which govern skeletal muscle
hypertrophy. However, alternative molecular signalling pathways such as
the Ca(2+)/calmodulin-dependent transcriptional pathways should also be
considered as potential mediators of muscle growth. These latter
pathways have received relatively little attention and the purpose
herein is to highlight the progress being made in the understanding of
these pathways and associated molecules: calmodulin, calmodulin kinases
(CaMKs), calcineurin and nuclear factor of activated T-cell (NFAT),
which are involved in skeletal muscle regulation. We describe: (1) how
conformational changes in the Ca(2+) sensor calmodulin result in the
exposure of binding pockets for the target proteins (CaMKs and
calcineurin). (2) How Calmodulin consequently activates either the
Ca(2+)/calmodulin-dependent kinases pathways (via CaMKs) or
calmodulin-dependent serine/threonine phosphatases (via calcineurin).
(3) How calmodulin kinases alter transcription in the nucleus through
the phosphorylation, deactivation and translocation of histone
deacetylase 4 (HDAC4) from the nucleus to the cytoplasm. (4) How
calcineurin transmits signals to the nucleus through the
dephosphorylation and translocation of NFAT from the cytoplasm to the
nucleus.