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Osteoarthritis (OA) is one of the most common diseases of the musculoskeletal system, accomplished by a high level of disability. The leading pathogenetic factors of these age-associated diseases include the interrelated processes of “inflammatory aging” and mitochondrial dysfunction, which lead to the development of chronic inflammation and degradation of different joint tissues. The present article contains results about point mutations in mitochondrial genome of peri-articular muscular tissues in the patients with primary OA (experimental group) and post-traumatic osteoarthritis (control group). The study involved 67 volunteers over 53 years old with basic diagnosis of post-traumatic or primary gonarthrosis / coxarthrosis stage 3. Clinical diagnosis was made on the basis of medical history, complaints, clinical and X-ray examination data. The material for the study included the samples of muscles (80 to 100 mm³) obtained at knee or hip replacement surgery. Several techniques have been adapted for isolation, enrichment and purification of nucleic acids, thus allowing to obtain up to 500 ng of mitochondrial DNA (mtDNA) from the biopsies. The prepared mtDNA libraries were sequenced at NGS platform. Bioinformatic analysis was carried out using the following programs: MitoHPC (to detect rare single-nucleotide mutations of mtDNA), MitoSAlt (to detect rare deletions at the mtDNA level) and Splice-Break2 (to detect rare deletions at the level of mtDNA RNA transcripts). Common point mutations A189G (adenine to guanine at position 189) and T408A (thymine to adenine at position 408) were detected. In the control group, the A189G mutation was revealed in 7 patients and T408A mutation was found in 8 volunteers (both mutations were detected in 6 out of 9 persons). In experimental group, the A189G mutation was found in 43 of 58 patients, T408A – in 35 volunteers. In this group of volunteers, both mutations were registered in 19 subjects. The level of mutation frequency, expressed as allele frequency (VAF) in the experimental group significantly exceeded that of the control group. Moreover, in experimental group, unlike control group, a significant correlative relationship was established between the presence of an increased level of mutations in the mitochondrial genome, and a number of clinical and laboratory parameters in volunteers. The described mutations in the mitochondrial genome of periarticular muscle tissue seem to be associated both with aging process and with the direct development of age-associated pathology, i.e., osteoarthritis. The increased levels of mutations in positions 189 and 408 of the regulatory region of mitochondrial genes detected in our patients are apparently associated with both increased level of mutations typical of pathological aging and, possibly, with genotoxic effects of high-dose therapy with non-steroidal anti-inflammatory drugs on mitochondrial genome.