Genes related to muscle growth and regeneration
The growth and regeneration of muscle tissue can be achieved either by increasing the expression of genes that have a stimulating action, such as the insulin-like growth factor (IGF-1), or by inhibiting genes that usually act as repressors of growth processes, for example myostatin.
Muscle IGF-1 (mIGF-1) : The specific muscle isoform of the insulin-like growth factor (mIGF-1) plays a very important role in muscle regeneration. The IGF-1 gene has the task of repairing the muscle when it undergoes microscopic trauma during exercise.
Myostatin : Myostatin is a protein discovered in 1997 during cellular differentiation and proliferation studies. To understand what its real function was, mice were mated in which the gene coding for myostatin was inhibited.
The homozygous offspring (bearer of both mutated genes) showed superior muscular development compared to heterozygous mice (carriers of only one mutated gene) and normal ones. The body size was 30% higher, the muscle was hypertrophic and the weight was 2 or 3 times greater than in natural guinea pigs. Later histological analysis showed an increase in both the size of single muscle cells (hypertrophy) and their number (hyperplasia). At the same time there was a slight decrease in adipose tissue, while fertility and life span remained almost unchanged.
In 2004, studying a 5-year-old German child with abnormal strength and muscle mass development, the presence of a mutation in the gene that codes for myostatin was identified for the first time in humans. The influence on phenotypic expression was identical to that observed in laboratory mice and in the studied cattle breeds, so that the muscular strength of the child was similar if not even higher than that of an adult. A very interesting aspect is that the child's mother, from whom he inherited one of the two mutated alleles, was a professional sprinter and that some of his ancestors are remembered for their extraordinary strength.
Myostatin is a protein that therefore interacts with muscle development, inhibiting it; it is mainly produced by skeletal muscle cells and its action is regulated by the presence of an inhibitor called follistatin. The higher the level of follistatin, the lower the levels of myostatin, so the greater the muscular development. It seems that follistatin is able to interact with satellite cells by stimulating the proliferation of new muscle cells (hyperplasia). Normally the increase in muscle mass is due only to the increase in cell size (hypertrophy), while a slight hyperplasia may occur only in particular cases (muscle injuries).
Recently the myostatin inhibition approach in the treatment of muscular dystrophic diseases in animal models has aroused particular interest; both intraperitoneal injections of a myostatin inhibitor and specific deletions of the myostatin gene were performed, resulting in an improvement in muscular dystrophic disease. Current research is focusing on the study and development of these potentials, but there are still many hypotheses and few certainties. Studies on the role of myostatin in the human body are few, often discordant, and still awaiting confirmation. Muscle growth is in fact the result of a subtle balance between anabolic and catabolic factors and a single hormone, a gene or a particular substance is not enough to influence it significantly. To confirm this, there are studies in the literature that show that there are no important differences in the amount of muscle mass between normal subjects and others with myostatin deficiency.
Growth hormone (somatotropin - GH): GH or somatotropic hormone is a protein (a linear peptide composed of 191 amino acids) produced by the somatotropic cells of the anterior pituitary. It has pulsatile secretion, with more frequent and wider peaks in the first hours of sleep.
Sports activity represents a strong stimulus for the secretion of growth hormone. During long-term exercises the secretory peak is observed between the 25th and 60th minute, while in the case of anaerobic efforts this peak is recorded between the end of the 5th and the 15th minute of recovery.
With equal physical effort, GH secretion is greater:
- in women than in men
- in young people compared to elderly subjects
- in sedentary compared to trained ones
GH secretion during exercise is influenced by:
- INTENSITY'
A significant response of GH to exercise is already observed for low intensity exercises (50% of VO2max) and becomes maximum around the anaerobic threshold (70% of VO2max). A further increase in intensity does not cause any significant increase in the secretory peak. The greatest response of GH to physical effort is observed during exercises with great demand on anaerobic glycolysis and with massive production of lactate (eg body building). GH secretion is inversely proportional to the recovery period and directly proportional to the duration of the exercise.
- WORK OUT
The response of GH to exercise is inversely related to the degree of training. At the same exercise intensity, a trained person produces much less GH than a deconditioned subject, since lactidemia (quota of lactate in circulation) is lower.
The effects of GH are partly direct, such as the diabetogenic and lipolytic effect, and partly mediated by similar insulin factors: Insulin Growth Factor (IGF-1, IGF-2).
- TEMPERATURE
The response in GH secretion to the change in environmental temperature is directly proportional to the decrease in temperature itself.
The GH-IGF axis acts physiologically on the glucose metabolism, causing hyperglycemia; on the protidic metabolism, increasing the cellular uptake of amino acids and accelerating transcription and translation of mRNA, thus favoring protein anabolism and the development of muscular masses; finally it also acts on lipid metabolism, causing lipolysis with an increase in free fatty acids and ketone bodies.
There are many side effects associated with the administration of high amounts of GH: myopathy, peripheral neuropathies, fluid retention, edema, carpal tunnel syndrome, arthralgia, paresthesia, gynecomastia, benign intracranial hypertension with papilledema and headache, acute pancreatitis, glucose intolerance, plasma increases in cholesterol and triglycerides, arteriovenous diseases, cardiomegaly and cardiomyopathy. The musculoskeletal and cardiac effects associated with GH administration can be irreversible, often even after the hormone is withdrawn. It is also important to remember that da GH can induce the formation of neoplasms, especially in the colon, skin and blood.
Strategies for the detection of genetic doping
The inclusion of genetic doping by the World Anti-Doping Agency (AMA) in the list of prohibited substances and methods has been followed by the difficulty of developing methods for its detection, since both the transgene and the expressed protein would have been most likely indistinguishable from their endogenous counterparts.
The ideal sample for genetic doping detection should be easily accessible with samples that do not use an invasive approach; moreover, the survey should reflect not only the situation at the time of the withdrawal, but also that of a previous period of time the same. Body fluids (blood, urine and saliva) satisfy the first point, therefore the developed methodology should apply to at least one of these samples. Detection methods should be specific, sensitive, fairly fast, potentially cost-effective and should allow large-scale analysis.
The legal implications related to the use of any method that allows the monitoring of doping on athletes are such that, where possible, a direct method that unequivocally identifies the doping agent will always be preferred to an indirect method, which measures the change occurred in the cells, tissues or the entire body due to doping. With regard to genetic doping, the detection of the transgene, of the transgenic protein or of the vector itself would be a direct approach, but the opportunity to use this type of approach is minimal, as in the case of detection of forbidden peptide hormones such as erythropoietin and somatotropin. The indirect approach (biological passport) instead provides a certain reliability in the result of the tests, based on a statistical model, therefore more open to legal control. Furthermore, an agreement has not yet been reached between the important figures of the sporting community regarding an acceptable level of reliability.
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