Proshkina Ekaterina, Pakshina Natalya, Koval Lyubov, Shchegoleva Evgeniya, Zemskaya Nadezhda, Shaposhnikov Mikhail, Moskalev Alexey
Institute of Biology, Komi Science Centre, Ural Branch, Russian Academy of Sciences, Syktyvkar, Russian Federation, 167982.
Institute of Longevity With a Clinic of Rehabilitation and Preventive Medicine, Russian Scientific Centre of Surgery Named After Academician B. V. Petrovsky, Moscow, Russian Federation, 119435.
Biogerontology. 2025 Jun 27;26(4):130. doi: 10.1007/s10522-025-10272-5.
Small non-coding RNAs coordinate essential cellular processes, including gene expression regulation, genome stability maintenance, and transposon suppression. These processes determine aging, lifespan, and resistance of cells and organisms to stress. In this work, we conducted a comprehensive study of the geroprotective effects of overexpression of two Dicer family genes (Dcr-1 and Dcr-2, which are responsible for the biogenesis of miRNAs and siRNAs) in different tissues of Drosophila melanogaster (nervous system, fat body, intestine, muscles). Activation of the Dicer genes affected the lifespan in a tissue- and sex-depending manner. Females with Dcr-1 overexpression in the nervous system exhibited a significant and reproducible increase in both median (10.0-13.4%, p < 0.001) and maximum lifespan (10.0-13.4%, p < 0.01). However, in other cases, the effect was insignificant or negative. Additionally, flies with neuronal Dcr-1 activation had increased expression of several longevity genes (Sirt1, bsk, tgo, Gadd45, Xpc, Azot, foxo, Hsf, Tsc1) and significantly increased survival after acute exposure to 700 Gy γ-radiation (40-200%, p < 0.05). But they had reduced resistance to starvation. This indicates a crucial role of the miRNA machinery and the Dicer family in providing protection against genotoxic effects and coordinating metabolic processes.
小非编码RNA协调细胞的基本过程，包括基因表达调控、基因组稳定性维持和转座子抑制。这些过程决定了细胞和生物体的衰老、寿命以及对压力的抵抗力。在这项工作中，我们对果蝇（黑腹果蝇）不同组织（神经系统、脂肪体、肠道、肌肉）中两个Dicer家族基因（Dcr-1和Dcr-2，它们负责miRNA和siRNA的生物合成）过表达的老年保护作用进行了全面研究。Dicer基因的激活以组织和性别依赖的方式影响寿命。在神经系统中过表达Dcr-1的雌性果蝇的中位寿命（10.0 - 13.4%，p < 0.001）和最大寿命（10.0 - 13.4%，p < 0.01）均有显著且可重复的增加。然而，在其他情况下，这种影响不显著或为负面。此外，神经元Dcr-1激活的果蝇中几个长寿基因（Sirt1、bsk、tgo、Gadd45、Xpc、Azot、foxo、Hsf、Tsc1）的表达增加，并且在急性暴露于700 Gy γ射线后存活率显著提高（40 - 200%，p < 0.05）。但它们对饥饿的抵抗力降低。这表明miRNA机制和Dicer家族在提供针对基因毒性作用的保护以及协调代谢过程中起着关键作用。
