Exercise Science, LLC

Personal Training and Rehabilitation, New Orleans, LA.


Muscle Strength vs. Size

Size vs. Strength - Genetic Aspects

Myosin Light Chain Kinase (MLCK) is one of the genes associated with variations in strength.
Size vs. Strength

Myosin Light Chain Kinase (MLCK) is one of the genes associated with variations in strength. MLCK genotype phosphorylates myosin’s regulatory light chain (RLC). RLC functions to modulate force production in fast twitch fibers by regulating attachments at the cross-bridge between actin and myosin. An increase in RLC phosphorylation results in a greater number of attachments, increasing force production. (Childers & McDonald, Muscle Nerve 2004) See Fig. 1

Fig. 1

Individuals that are homozygote for the T allele (TT genotype) have greater baseline strength as compared to individuals that are homozygote for the C allele (CC) as well as the heterozygote (CT) genotype, due to a greater number of cross-bridge attachments. (Clarkson, et al, 2005) See Fig. 2. Subjects possessing the TT genotype will be stronger, without necessarily having larger muscles.

Fig. 2

Although this increased baseline strength may represent a survival advantage on one hand, it results in a larger force decrement after an eccentric exercise stimulus, as well as greater exercise induced microtrauma, as measured by both creatine kinase and myoglobin activity. See Figs. 3 and 4.

Fig. 3

Fig. 4

One of the strongest genetic influencers on size versus strength is interleukin-15 (IL-15) genotype. IL-15 is a cytokine and an important component of the immune system, playing a role in modulating inflammation (Parera, 2012). IL-15 is found in abundance in skeletal muscle (Nieman et al. 2003), which has some of the highest levels of any tissue (Grabstein et al. 1994, Quinn et al. 1997). A number of studies have shown IL-15 to be both anabolic and anti-catabolic (Quinn et al. 1995, Carbo et al. 2000, Quinn et al. 2002).

Riechman et al. 2004 examined the association between variations in the IL-15 receptor genotype and muscle adaptations in response to 10 weeks of high intensity resistance training. One hundred fifty three subjects (76 men and 77 women between 18-31 years) participated in a 10 week resistance training program. The subjects completed 3 sets of 13 exercises for the entire body, 3 times per week, with 80% of a 1RM for 6-10 repetitions. Resistance was increased when the subjects were able to perform 10 reps. They were tested for total lean mass, arm circumference, leg circumference, and isometric strength.

Subjects with the A allele had significantly greater increases in total lean mass, arm circumference, and leg circumference. There was a significant linear trend with each additional A allele, such that muscle size increases were greatest in A/A > C/A > C/C. The researchers had originally hypothesized that the genotype with the largest increase in cross sectional area, would also have the largest gains in muscle strength. However, this was not the case. There was a non significant trend in the opposite direction, such that the average strength gain was lower with each additional A allele, A/A < C/A < C/C. Stated more simply, the genotype with greatest increase in muscle size (A/A) had the lowest increase in muscle strength. Conversely, the genotype that had the greatest increase in muscle strength (C/C) had the smallest increase in muscle size. See Figs. 5 and 6

Fig. 5

Fig. 6

This was a surprising finding and makes sense from an evolutionary perspective.. The A/A genotype, with greater increases in muscle size, is more rare than both the C/C and C/A genotypes, representing 21% of the subjects (See table 1 for the frequency of the A allele). Skeletal muscle is metabolically active tissue. It requires nutrients and energy to maintain. Adding less muscle mass per unit of strength gained would represent increased efficiency and a survival advantage.

Table 1

The authors concluded the following:

“Hypertrophy has been considered the ideal response to resistance training and cellular studies of muscle growth, but muscle quality has been examined recently to reflect a measure of mass to performance efficiency. If neurological and biochemical adaptations are not sufficient to respond to the overload stimulus, hypertrophy may be a compensating adaptation.”


Priscilla M. Clarkson, Eric P. Hoffman, Edward Zambraski, Heather Gordish-Dressman, Amy Kearns, Monica Hubal, Brennan Harmon and Joseph M. Devaney
ACTN3 and MLCK genotype associations with exertional muscle damage.
Journal of Applied Physiology 99:564-569, 2005. First published Apr 7, 2005; doi:10.1152/japplphysiol.00130.2005

Martin K. Childers DO, PhD, Kerry S. McDonald PhD
Regulatory light chain phosphorylation increases eccentric contraction–induced injury in skinned fast-twitch fibers.
Muscle Nerve 29: 313–317, 2004
First published: 24 November 2003 https://doi.org/10.1002/mus.10517

Grabstein KH, Eisenman J, Shanebeck K, Rauch C, Srinivasan S, Fung V, Beers C, Richardson J, Schoenborn MA, Ahdieh M, Johnson L, Alderson MR, Watson JD, Anderson DM, and Giri JG.
Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor.
Science 264: 965–968, 1994.

Quinn LS, Haugk KL, and Damon SE.
Interleukin-15 stimulates C2 skeletal myoblast differentiation.
Biochem Biophys Res Commun 239: 6–10, 1997.

Nieman DC, Davis JM, Henson DA, Walberg-Rankin J, Shute M, Dumke CL, Utter AC, Vinci DM, Carson JA, Brown A, Lee WJ, McAnulty SR, and McAnulty LS.
Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run.
J Appl Physiol 94: 1917–1925, 2003.

Quinn LS, Haugk KL, and Grabstein KH.
Interleukin-15: a novel anabolic cytokine for skeletal muscle.
Endocrinology 136: 3669–3672, 1995.

Carbó N, Lopez-Soriano J, Costelli P, Busquets S, Alverez B, Baccino FM, Quinn LS, Lopez-Soriano FJ, and Argiles JM.
Interleukin-15 antagonizes muscle protein waste in tumor-bearing rats.
Br J Cancer 83: 526–531, 2000.

Quinn LS, Anderson BG, Drivdahl RH, Alvarez B, and Argiles JM.
Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders.
Exp Cell Res 280: 55–63, 2002.

Perera PY, Lichy JH, Waldmann TA, Perera LP.
The role of interleukin-15 in inflammation and immune responses to infection: implications for its therapeutic use.
Microbes Infect. 2012 Mar;14(3):247-61. doi: 10.1016/j.micinf.2011.10.006. Epub 2011 Oct 25. PMID: 22064066; PMCID: PMC3270128.

blog comments powered by Disqus