Institute of Molecular Genetics, National Research Center "Kurchatov Institute", Moscow, 123182, Russia.
Vavilov Institute of General Genetics, Russian Academy of Sciences, 11999 Moscow, Russia.
Biochemistry (Mosc). 2022 Dec;87(12):1611-1621. doi: 10.1134/S0006297922120161.
Fundamental mechanisms underlying genetic control of lifespan are intensively studied and discussed due to the increasing importance of extending healthy human life. The stc gene of the model organism Drosophila melanogaster encodes a transcription factor, homolog of the human transcription factor NF-X1, involved in regulation of neuronal development and other processes, as well as in control of lifespan. In this work, we demonstrate that the stc knockdown in embryonic and nerve cells leads to changes in lifespan, with the nature of changes depending on the cell type and sex of individuals. Based on our results, we suggest that stc gene is involved in transcription regulation throughout life, and, as a result, also affects a complex integral trait, lifespan. At the same time, we show that the reduction of stc expression in neurons can alleviate the negative effect of glutamate on longevity, possibly preventing development of glutamate excitotoxicity, thus modifying the cell death program and preventing death of individuals due to phenoptosis.
由于延长人类健康寿命的重要性日益增加,遗传控制寿命的基本机制受到了深入的研究和讨论。模式生物果蝇的 stc 基因编码一种转录因子,与人类转录因子 NF-X1 同源,参与神经元发育和其他过程的调节,以及寿命的控制。在这项工作中,我们证明了 stc 在胚胎和神经细胞中的敲低会导致寿命的变化,变化的性质取决于细胞类型和个体的性别。基于我们的结果,我们认为 stc 基因参与了整个生命周期的转录调控,因此也影响了一个复杂的整体特征,即寿命。同时,我们表明,神经元中 stc 表达的减少可以减轻谷氨酸对寿命的负面影响,可能防止谷氨酸兴奋性毒性的发展,从而改变细胞死亡程序,防止因表型死亡而导致个体死亡。