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Vol 59(2025) N 6 p. 981-992; DOI 10.1134/S0026893325700414  N.S. Timusheva1, M.V. Shaposhnikov1, E.N. Proshkina1*, A.A. Moskalev2** Effect of Histone Lysine Methyltransferase G9a Inhibitor on Lifespan and Radioresistance in Drosophila melanogaster 1Institute of Biology, Komi Science Centre, Ural Branch, Russian Academy of Sciences, Syktyvkar, 167982 Russia2Institute of Longevity and Clinic of Rehabilitation and Preventive Medicine, Petrovsky National Research Center of Surgery, Moscow, 119435 Russia *proshkina.e.n@ib.komisc.ru **amoskalev@list.ru Received - 2025-04-07; Revised - 2025-06-10; Accepted - 2025-06-13 Histone lysine methyltransferase G9a is an important regulator of transcription of various genes and cell processes, but its role in determining aging and radioresistance is still poorly understood. The selective G9a inhibitor UNC0646 was tested for effect on lifespan and resistance to γ radiation and paraquat in Drosophila melanogaster. UNC0646 used at concentrations of 0.1-100 μM exerted a geroprotective effect on females, increasing the average lifespan by 1.6-13.9% (p < 0.05). Resistance to γ radiation was found to decrease in D. melanogaster receiving UNC0646 with food for 2 weeks. A positive effect of the inhibitor on lifespan in females might be due to the activation of genes involved in the DNA damage response and repair (D-Gadd45, mei-9, spn-B, and Ku80) and proteostasis (Hsp27, Hsp68, Atg1, and Ire1). lifespan, stress resistance, у radiation, histone methyltransferase G9a, UNC0646, Drosophila melanogaster |
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