Molekulyarnaya Meditsina (Molecular medicine)Molekulyarnaya Meditsina (Molecular medicine)Молекулярная медицина1728-29182499-9490Russkiy Vrach Publishing House11336110.29296/24999490-2021-01-03ArticlesСтатьиReview ArticleMolecular and genetic markers of sarkopeniaМолекулярно-генетические маркеры саркопенииKucherAksana NikolaevnaКучерАксана Николаевна

Leading Researcher, Laboratory of Population Genetics. Research Institute of Medical Genetics, professor, doctor of Biological Sciences.

ведущий научный сотрудник лаборатории популяционной генетики, НИИ медицинской генетики, профессор, доктор биологических наук

aksana.kucher@medgenetics.ruTomsk National Research Medical Center, Russian Academy of ScienceТомский национальный исследовательский медицинский центр Российской академии наук15012021191VOL 19, NO1 (2021)ТОМ 19, №1 (2021)172918112022Copyright ©; 2021, Russkiy Vrach Publishing HouseCopyright ©; 2021, ИД "Русский врач"2021Russkiy Vrach Publishing HouseИД "Русский врач"https://journals.eco-vector.com/1728-2918/article/view/113361

Sarcopenia is a progressive and generalized pathology of skeletal muscles of multi-factor nature. The present review focuses on the analysis of molecular genetic markers that may contribute both to sarcopenia risk formation and the variability of diagnostically relevant signs for a given disease. According to GWAS, polymorphic variants of369genes are associated with such a diagnostically significant sign for sarcopenia as “muscle mass”. According to information provided in the database «DisGeNet» on sarcopenia-associated genes, and in «Gene Ontology» on genes involved in regulation of muscle atrophy (GO:0014737, GO:0014732, GO:0014736) and muscle regeneration (GO:0014839), 69 genes can be considered as candidate sarcopenia genes. Genes associated with muscle mass and candidate genes for sarcopenia have pleiotropic properties, are involved in the regulation of a wide range of biological processes (including the metabolism of hormones, carbohydrates, lipids, proteins; response to stimuli (sex hormones, nutrients), in the regulation of gene expression , protein/serine kinase activity and MAPK signaling pathway); these genes are associated with multi-factorial diseases that are comorbid with sarcopenia; sensitive or determine the response to drugs, hormones, nutrienes (including creatine, corticosteroids, aldosterone, aldosterone antagonists, metformin, protein. Differences are recorded between healthy individuals and sarcopenia sufferers in the level of DNA methylation and in the level of gene expression (including in muscles), the products of which are involved in metabolic pathways significant for maintaining homeostasis in muscles. The methylation pattern and the level of gene expression is influenced by a wide range of factors, including the age of individuals, their hormonal background, the level of physical activity and the type of physical exercise, the consumption of nutrients. Thus, by now, a wide range of molecular genetic markers have been identified at the genomic, epigenome, and transcriptomic levels, which, along with traditional risk factors (and in interaction with them), can contribute to the risk of developing sarcopenia.

Саркопения - это прогрессирующая генерализованная патология скелетных мышц многофакторной природы. Настоящий обзор посвящен анализу молекулярно-генетических маркеров, которые могут вносить вклад в формирование риска развития саркопении и в изменчивость диагностически значимых для данного заболевания признаков. По данным GWAS для полиморфных вариантов 369 генов установлены ассоциации с фенотипом «мышечная масса». Согласно информации, представленной в базе DisGeNet об ассоциированных с саркопенией генах, и в Gene Ontology - о генах, участвующих в регуляции процессов атрофии (GO:0014737, GO:0014732, GO:0014736) и регенерации (GO:0014839) мышц, 69 генов могут рассматриваться в качестве генов-кандидатов саркопении. Гены, ассоциированные с мышечной массой, и гены-кандидаты саркопении обладают плейотропными свойствами, вовлечены в регуляцию широкого спектра биологических процессов (включая метаболизм гормонов, углеводов, липидов, протеина; ответ на стимулы (половые гормоны, нутриенты), регуляция экспрессии генов, протеин/серинкиназной активности и MAPK-сигнального пути); ассоциированы с коморбидными с саркопений заболеваниями многофакторной природы, чувствительны или определяют ответ на лекарственные средства, гормоны, нутриены (включая креатин, кортикостероиды, альдостерон, антагонисты альдостерона, метформин, белковые добавки). Между здоровыми индивидами и страдающими саркопенией зарегистрированы различия по уровню метилирования ДНК и по уровню экспрессии генов (в том числе и в мышцах), продукты которых участвуют в метаболических путях, значимых как для поддержания гомеостаза в мышцах. На характер метилирования и уровень экспрессии генов оказывает влияние широкий спектр факторов, включая возраст обследуемых, их гормональный фон, уровень физической активности и тип физических упражнений, потребление нутриентов. Таким образом, к настоящему времени на геномном, эпигеномном и транскриптомном уровнях выявлен широкий спектр молекулярно-генетических маркеров, которые наряду с традиционными факторами риска (и во взаимодействии с ними) могут вносить вклад в риск развития саркопении.

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