Effect of the Histone Lysine Methyltransferase G9a Inhibitor on the Lifespan and Radioresistance of Drosophila melanogaster

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).