The pre-exhaustion technique is commonly used by bodybuilders seeking to enhance the muscle growth of target muscles. The rationale for this technique is that performing a single-joint exercise first fatigues the agonist in isolation, thereby placing greater stress on the agonist and increasing its activation during multi-joint exercise and potentiating its hypertrophy [73]. Another variation is the reverse pre-exhaustion (e.g., triceps pushdown before the bench press), and the justification for this approach is that the fatigued synergist contributes less to the subsequent multi-joint exercise, thereby placing greater stress on the agonist group [74]. However, a study by Golas et al. [75] partially disagreed with this statement as the results indicated that a pre-exhaustion exercise (incline dumbbell fly) did not affect the pectoralis major activity during the flat bench press exercise at 95% 1RM. Despite that, pre-exhaustion of the synergist muscles (triceps brachii and anterior deltoid before the bench press) led to their higher activation during the multi-joint movement (bench press) as compared to the baseline [75]. Furthermore, results of a study by Soares et al. [50] suggested that pre-exhaustion (triceps pushdown followed by the bench press) decreased the maximal number of repetitions performed during a set to volitional fatigue.
Science and Development of Muscle Hypertrophy download.zip
The quest to increase lean body mass is widely pursued by those who lift weights. Research is lacking, however, as to the best approach for maximizing exercise-induced muscle growth. Bodybuilders generally train with moderate loads and fairly short rest intervals that induce high amounts of metabolic stress. Powerlifters, on the other hand, routinely train with high-intensity loads and lengthy rest periods between sets. Although both groups are known to display impressive muscularity, it is not clear which method is superior for hypertrophic gains. It has been shown that many factors mediate the hypertrophic process and that mechanical tension, muscle damage, and metabolic stress all can play a role in exercise-induced muscle growth. Therefore, the purpose of this paper is twofold: (a) to extensively review the literature as to the mechanisms of muscle hypertrophy and their application to exercise training and (b) to draw conclusions from the research as to the optimal protocol for maximizing muscle growth.
Written by Brad Schoenfeld, PhD, a leading authority on muscle hypertrophy, Science and Development of Muscle Hypertrophy provides strength and conditioning professionals, researchers, and instructors with a definitive resource for information regarding muscle hypertrophy.
Although muscle hypertrophy can be attained through a range of training programs, this text allows readers to understand and apply the specific responses and mechanisms that promote optimal muscle hypertrophy in their athletes and clients. It explores how genetic background, age, sex, and other factors have been shown to mediate the hypertrophic response to exercise, affecting both the rate and the total gain in lean muscle mass. Sample programs in the text show how to design a three- or four-day-per-week undulating periodized program and a modified linear periodized program for maximizing muscular development.
Myostatin-related muscle hypertrophy is a rare condition characterized by reduced body fat and increased muscle size. Affected individuals have up to twice the usual amount of muscle mass in their bodies. They also tend to have increased muscle strength. Myostatin-related muscle hypertrophy is not known to cause any medical problems, and affected individuals are intellectually normal.
Variants (also known as mutations) in the MSTN gene cause myostatin-related muscle hypertrophy. The MSTN gene provides instructions for making a protein called myostatin, which is active in muscles used for movement (skeletal muscles) both before and after birth. This protein normally limits muscle growth, ensuring that muscles do not grow too large. Variants that reduce the production of functional myostatin lead to an overgrowth of muscle tissue.
Myostatin-related muscle hypertrophy has a pattern of inheritance known as incomplete autosomal dominance. People with a variant in both copies of the MSTN gene in each cell (homozygotes) have significantly increased muscle mass and strength. People with a variant in one copy of the MSTN gene in each cell (heterozygotes) also have increased muscle bulk, but to a lesser degree.
A highly conserved signaling pathway involving insulin-like growth factor 1 (IGF1), and a cascade of intracellular components that mediate its effects, plays a major role in the regulation of skeletal muscle growth. A central component in this cascade is the kinase Akt, also called protein kinase B (PKB), which controls both protein synthesis, via the kinases mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3β (GSK3β), and protein degradation, via the transcription factors of the FoxO family. In this paper, we review the composition and function of this pathway in skeletal muscle fibers, focusing on evidence obtained in vivo by transgenic and knockout models and by muscle transient transfection experiments. Although this pathway is essential for muscle growth during development and regeneration, its role in adult muscle response to mechanical load is less clear. A full understanding of the operation of this pathway could help to design molecularly targeted therapeutics aimed at preventing muscle wasting, which occurs in a variety of pathologic contexts and in the course of aging.
Two in vivo genetic approaches have been used to understand how muscle mass is regulated. One is based on the generation of transgenic and knockout mice, in which expression of muscle regulatory genes is selectively modified. The potential of the traditional gene overexpression or deletion approaches has been fully exploited with the introduction of the Cre/loxP technique and the use of inducible transgenes, which allows for the modulation of gene expression specifically in muscle tissues and at different developmental stages. It is thus possible to distinguish between the effects on the regulation of muscle growth during development from the effects on the maintenance of muscle mass in adulthood. An alternative approach to address muscle-mass regulation in the adult is based on in vivo transfection of skeletal muscles by electroporation with plasmids coding for specific components of signaling pathways, or for mutants bearing constitutively active or dominant negative properties. Transfection with plasmids able to generate specific small interfering RNAs in muscle fibers is also increasingly being used as a loss-of-function model. The ability of various factors in preventing muscle atrophy can be explored by transfecting denervated muscles.
The activity of the IGF1-Akt pathway can be modulated by a variety of other factors and pathways acting on different steps (Figure 3). IGF binding proteins (IGFBPs), the most important probably being IGFBP5, can block IGF1 action by inhibiting its binding to the IGF1 receptor. Mechanical signals via integrin β1 and integrin-linked kinase (ILK) lead to phosphorylation of the IGF1 receptor and activation of the PI3K-Akt pathway in muscle cells [13]. Whether another downstream integrin effector, the integrin-dependent focal adhesion kinase (FAK), affects the IGF1-Akt pathway in skeletal muscle remains to be established. FAK null mice are embryonic lethal, and skeletal muscle-specific conditional mutants have not been reported. Overexpression of FAK by electrotransfer was found to induce slight hypertrophy in adult rat muscles, but the effect on the IGF1-Akt pathway was not investigated [14]. Activation of IRS types is inhibited by phosphorylation of serine residues induced by inflammatory cytokines such as tumor necrosis factor α (TNFα) via Jun N-terminal kinase (JNK) [15]. PTEN (phosphatase and tensin homolog deleted from chromosome 10) is a lipid phosphatase that converts PIP3 to PIP2, thus opposing the action of PI3K, and interfering with Akt docking to the plasma membrane. Myostatin, also called growth and differentiation factor 8 (GDF8), acts as negative regulator of muscle growth, as shown by the hypertrophic phenotype induced by inactivation of the myostatin gene [16]. Myostatin, together with activin A, another member of the TGFβ family, acts via its receptor activin receptor IIB (ActRIIB) on Smad2 and Smad3, inhibitors of Akt; conversely, mTOR inhibits Smads [17, 18]. In cultured muscle cells, addition of IGF1 dominantly blocks the effect of myostatin [17]. In adult skeletal muscle, muscle hypertrophy can be induced and muscle wasting prevented by blocking myostatin either via postdevelopmental myostatin gene knockout, or with follistatin (a myostatin antagonist) or anti-myostatin antibodies or a soluble ActRIIB decoy receptor (see [19, 20] and references therein).
The Igf1 gene can produce multiple transcripts by alternative RNA processing, thus generating divergent peptides at the carboxyl terminus, called the E peptides. Two isoforms, IGF1A and IGF1B, are found in most mammals, and an additional form, IGF1C, is present in primates and humans [49]. The E peptides appear to be essential for muscle growth regulation because viral delivery of IGF1A or IGF1B promoted functional hypertrophy in mouse muscles, whereas delivery of mature IGF1 devoid of E peptide failed to cause an increase in muscle mass [50]. The effect of an IGF1 isoform (IGF1A) was investigated in a transgenic mouse model, in which expression of this isoform was driven by the myosin light chain 1 fast promoter [51]. The transgenic mice showed postnatal increase in muscle mass and strength, and were protected from age-related muscle atrophy and weakness. Moreover, aging transgenic muscles retained a regenerative capacity comparable with that of young animals. Surprisingly, Akt activation was not detected in these mice [52], suggesting that IGF1 may signal via alternative pathways. A potential alternative pathway could be the serum- and glucocorticoid-responsive kinase 1 (SGK1), a PI3K-dependent kinase with structural homology to Akt, which is strongly expressed in many tissues, including skeletal muscle and heart [53]. SGK1 is activated by IGF1, PI3K and PDK1, and can induce phosphorylation of S6K and GSK3β in cardiomyocytes [54] and phosphorylation of FoxO3 in various cell types [55]. However, this alternative pathway has not been explored in skeletal muscle. IGF1-dependent signaling via the mitogen-activated protein kinase/extracellular signal-regulated receptor kinase (MAPK/ERK) pathway has also been implicated in IGF1-dependent muscle growth regulation [56, 57], however a constitutively active Ras double mutant that selectively activates the ERK pathway did not induce hypertrophy of regenerating muscle fibers [58]. 2ff7e9595c
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