Molecular and genetic markers of sarkopenia


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Abstract

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.

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About the authors

Aksana Nikolaevna Kucher

Tomsk National Research Medical Center, Russian Academy of Science

Email: aksana.kucher@medgenetics.ru
Leading Researcher, Laboratory of Population Genetics. Research Institute of Medical Genetics, professor, doctor of Biological Sciences.

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