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Smaller chunks of your workout then can be dedicated to lower reps for continued strength progression and higher reps for stimulative variety. The traditional 6-12 rep zone is kind of a myth in the sense that research shows that you can go well outside that range and still grow, as long as you’re training close to muscular failure. In fact, the average rep count that subjects got with that load was 67 reps; not a very practical way to train.
Although the exact mechanisms underlying sarcopenia are not fully understood, evidence suggests that the loss of mitochondrial integrity in skeletal myocytes has emerged as a pivotal contributor to the complex etiology of sarcopenia. This hypothesis is also supported by the fact that in humans, CD34+ interstitial, mesenchymal cells are AR positive and expression of the AR is androgen dose-dependent (13, 102). Recently, it has been described that satellite cells can be transplanted into the muscle of mice, and they are able to proliferate. However, there are significant controversies regarding both the efficiency and the reality of skeletal muscle differentiation by many of these stem cell types. There are a number of potential sources of muscle stem cells for cell replacement therapies such as bone marrow-derived stem cells, hematopoietic stem cells, and MSCs.
Since about two-thirds of the mitochondrial proteins are located in the mitochondrial membrane and matrix, regulation of the enormously protein-dense matrix environment is particularly important for retaining normal mitochondrial functions. This is partly responsible for the increased incidence of apoptosis in aged skeletal muscle cells (50). However, mitochondrial dysfunction is strongly linked to the excessive release of ROS, which results in oxidative damage to lipids, proteins, and DNA, leading to the development of degeneration and biological aging (42). Many studies reporting an increase in muscle strength with TRT suffered from methodological problems, such as lack of a control group, lack of control for the effects of exercise, lack of control of the dose(s) of the hormones administered to maintain normal levels of circulating testosterone, or the inclusion of a very small number of patients. This cell proliferation is followed by a subsequent increase in the myonuclei number of the mature skeletal muscle, through the fusion of the satellite cells with pre-existing fibers resulting in muscle hypertrophy (12, 54, 82). In addition for changes at the skeletal muscle level, it has been described that other cell types are involved in testosterone-induced muscle functions. As described by Shen (72) (MIP/MTMR14), a recently described protein, is responsible for sarcopenia pathophysiology by controlling intracellular phosphatidylinositol phosphate (PIP) levels via influencing SOCE and Ca2+ storage and release from the sarcoplasmic reticulum (72).
From a descriptive/histological point of view, sarcopenia induces a change in the proportion of skeletal muscle fibers, inducing a shift from type II (fast) to type I (slow) fibers as well as preferential loss of type II fibers (22). Regarding gender differences in muscle distribution, it has been observed that woman had up to 40% less muscle in the upper body but no more than 33% less mass in the lower body compared to man (16). Clinical studies of androgen supplementation in age-related diseases and muscle wasting are a focus of emerging interest (11). Indeed, most of the intrinsic as well as extrinsic (systemic) muscle changes that occur with age are believed to be involved in the development of sarcopenia (5, 6). However, the pathophysiological mechanisms underlying this muscle syndrome and its relationship with plasma level of androgens are not completely understood. Currently, there is increasing interest on the anabolic properties of testosterone for therapeutic use in muscle diseases including sarcopenia.
Several recent studies have suggested a link between AAA proteases-dependent mitochondrial protein quality control and muscle quality/function maintenance. Mitoproteases serve as the first line of defense against mild mitochondrial damage and involves the degradation of misfolded or damaged proteins (55). Therefore, decline in mitochondrial function and loss of mitochondrial content in motor neurons may contribute to a decrease in muscle strength (51, 52). An increase in Ca2+ concentration induces mPTP opening, which further exacerbates the imbalance of intracellular Ca2+ homeostasis, possibly caused by leaky ryanodine receptors in aged skeletal muscle (49). In deed, the production of mild oxidative stress acts as a cellular signal that increases skeletal muscle strength, while further increases reduce strength and promote muscle fatigue (48). Conversely, the accumulation of ROS in the muscle and neuron cells has the potential to damage cellular mitochondria (46). Figure 1 shows the general pathways initiated by mitochondrial alteration resulting in motor neuron and muscle cell death and culminating in sarcopenia (14).
Signals of 17β-estradiol and testosterone affect mitochondria function through multiple pathways. Schematic illustrating the roles that 17β-estradiol and testosterone play in mitochondrial protection of skeletal myocytes. Both steroids trigger complex molecular mechanisms involving crosstalk between mitochondria, the nucleus, and the plasma membrane, and the result of this action is mitochondrial protection (Figure 2). For a detailed description of the regulation of estrogens on mitochondrial function, see (136, 137). Moreover, 17β-estradiol also appears to regulate multiple other aspects of mitochondrial function through ERs, including ROS generation, antioxidant defense, and Ca2+ handling (126–131). 17β-estradiol also increases the transcription of mitochondrial nuclear-encoded genes, and mitochondria-encoded genes through the ERα/β mediated activation of NRF1 and TFAM (122, 123). It can also be produced locally from fat, brain, skeletal muscle, and testes by aromatization, which converts androstenedione and testosterone to 17β-estradiol (116, 117).
Through a process known as Translation, those blueprints are sent to a Ribosome, which is like a muscle protein-building factory that manufactures a string of amino acids based on the blueprint from the mRNA. From the mechano-sensors, a signal gets sent to a beast mode molecule called mTOR, which is a major regulator of cellular growth in general. Then there are Filaments, which bind to the famous actin proteins that slide during contraction, making them a really good candidate for sensing tension. When it comes to muscle growth, there isn’t just one pathway with one outcome, but rather many different interconnected pathways with many different downstream effects. We know that mechanical tension is the main thing driving muscle growth, but what happens next? Also, paying attention to things like the mind-muscle connection, at least on certain exercises, and eccentric control should also help, as those aspects of lifting have been shown to increase intramuscular tension. This means we need to lift with good consistent technique while using the acute training variables and progressive overload to push the level of intramuscular tension up over time.
There’s also this other path that’s triggered by amino acids in the protein we eat. From there, mTOR goes to the nucleus and tells the DNA machinery to produce a messenger RNA (mRNA) strand, which you can think of as a set of blueprints for building new muscle. "Conclusively identifying major hypertrophy stimuli and their sensors is one of the big remaining questions in exercise physiology."