Molecular BiologyMolecular BiologyМолекулярная биология0026-89843034-5553The Russian Academy of Sciences69967810.7868/S3034555325060061МОЛЕКУЛЯРНАЯ БИОЛОГИЯ КЛЕТКИResearch ArticleEffect of the Histone Lysine Methyltransferase G9a Inhibitor on the Lifespan and Radioresistance of Drosophila melanogasterВЛИЯНИЕ ИНГИБИТОРА ГИСТОН-ЛИЗИН-МЕТИЛТРАНСФЕРАЗЫ G9a НА ПРОДОЛЖИТЕЛЬНОСТЬ ЖИЗНИ И РАДИОУСТОЙЧИВОСТЬ Drosophila melanogasterTimushevaN. SТимушеваН. Сproshkina.e.n@ib.komisc.ruShaposhnikovM. VШапошниковМ. Вproshkina.e.n@ib.komisc.ruProshkinaE. NПрошкинаЕ. Нproshkina.e.n@ib.komisc.ruMoskalevA. AМоскалевА. Аamoskalev@list.ruInstitute of Biology, Komi Science Centre, Ural Branch, Russian Academy of SciencesИнститут биологии Коми научного центра Уральского отделения Российской академии наукInstitute of Longevity with a Clinic of Rehabilitation and Preventive Medicine, Russian Scientific Centre of Surgery named after Academician B.V. PetrovskyИнститут долголетия с клиникой реабилитации и превентивной медицины Российского научного центра хирургии им. академика Б.В. Петровского25122025596VOL 59, NO6 (2025)ТОМ 59, №6 (2025)95797027122025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://vietnamjournal.ru/0026-8984/article/view/699678

The enzyme lysine methyltransferase G9a is an important regulator of transcription of various genes and cellular processes, but its role in determining aging and radioresistance of an organism has not been well studied. In this work, the effect of UNC0646, a selective G9a inhibitor, on the lifespan of Drosophila melanogaster and its resistance to γ-radiation and paraquat was investigated. UNC0646 at the concentrations of 0.1–100 μM exerted a geroprotective effect on females, causing an increase in the average lifespan by 1.6–13.9% (p < 0.05). At the same time, after consuming this substance for two weeks, a decrease in Drosophila resistance to γ-radiation was observed. The positive effect of the drug on the lifespan of females may be due to the activation of genes of DNA damage response and repair (D-Gadd45, mei-9, spn-B, Ku80) and proteostasis genes (Hsp27, Hsp68, Atg1, Ire1).

Гистон-лизин-метилтрансфераза G9a играет важную роль в регуляции транскрипции различных генов и клеточных процессов, однако ее участие в детерминации старения и радиоустойчивости организма недостаточно изучено. В данной работе анализировали влияние селективного ингибитора G9a – UNC0646 – на продолжительность жизни особей Drosophila melanogaster и их устойчивость к действию γ-излучения и параквата. UNC0646 в концентрации 0.1–100 мкмоль/л оказывал геропротекторное действие на самок дрозофилы, вызвав увеличение средней продолжительности жизни на 1.6–13.9% (p < 0.05). В то же время у дрозофил, получавших UNC0646 в течение 2 недель, наблюдалось снижение устойчивости к γ-излучению. Положительное влияние UNC0646 на продолжительность жизни самок может быть обусловлено активацией генов ответа на повреждение ДНК и репарации ДНК (D-Gadd45, mei-9, spn-B, Ku80) и генов протеостаза (Hsp27, Hsp68, Atg1, Ire1).

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