Moskalev Alexey, Guvatova Zulfiya, Shaposhnikov Mikhail, Lashmanova Ekaterina, Proshkina Ekaterina, Koval Liubov, Zhavoronkov Alex, Krasnov George, Kudryavtseva Anna
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Institute of Biology of Komi Science Center of Ural Branch of Russian Academy of Sciences, Syktyvkar, Russia.
Front Genet. 2019 Mar 5;10:149. doi: 10.3389/fgene.2019.00149. eCollection 2019.
Some effects of aging in animals are tissue-specific. In neuronal overexpression of Gclc increases lifespan and improves certain physiological parameters associated with health benefits such as locomotor activity, circadian rhythmicity, and stress resistance. Our previous transcriptomic analyses of heads, primarily composed of neuronal tissue, revealed significant changes in expression levels of genes involved in aging-related signaling pathways (Jak-STAT, MAPK, FOXO, Notch, mTOR, TGF-beta), translation, protein processing in endoplasmic reticulum, proteasomal degradation, glycolysis, oxidative phosphorylation, apoptosis, regulation of circadian rhythms, differentiation of neurons, synaptic plasticity, and transmission. Considering that various tissues age differently and age-related gene expression changes are tissue-specific, we investigated the effects of neuronal overexpression on gene expression levels in the imago thorax, which is primarily composed of muscles. A total of 58 genes were found to be differentially expressed between thoraces of control and overexpressing flies. The level demonstrated associations with expression of genes involved in the circadian rhythmicity, the genes in categories related to the muscle system process and the downregulation of genes involved in proteolysis. Most of the functional categories altered by overexpression related to metabolism including Drug metabolism, Metabolism of xenobiotics by cytochrome P450, Glutathione metabolism, Starch and sucrose metabolism, Citrate cycle (TCA cycle), One carbon pool by folate. Thus, the transcriptomic changes caused by neuron-specific overexpression in the thorax were less pronounced than in the head and affected pathways also differed from previous results. Although these pathways don't belong to the canonical longevity pathways, we suggest that they could participate in the delay of aging of overexpressing flies.
衰老对动物的某些影响具有组织特异性。在神经元中过表达Gclc可延长寿命,并改善某些与健康益处相关的生理参数,如运动活性、昼夜节律性和抗应激能力。我们之前对主要由神经组织组成的头部进行的转录组分析显示,与衰老相关的信号通路(Jak-STAT、MAPK、FOXO、Notch、mTOR、TGF-β)、翻译、内质网中的蛋白质加工、蛋白酶体降解、糖酵解、氧化磷酸化、细胞凋亡、昼夜节律调节、神经元分化、突触可塑性和传递等相关基因的表达水平发生了显著变化。考虑到不同组织的衰老方式不同,且与年龄相关的基因表达变化具有组织特异性,我们研究了神经元过表达对主要由肌肉组成的成虫胸部基因表达水平的影响。共发现58个基因在对照果蝇和过表达果蝇的胸部之间存在差异表达。该水平显示出与昼夜节律相关基因的表达、与肌肉系统过程相关类别的基因以及蛋白水解相关基因的下调有关。过表达改变的大多数功能类别与代谢有关,包括药物代谢、细胞色素P450对外源生物的代谢、谷胱甘肽代谢、淀粉和蔗糖代谢、柠檬酸循环(TCA循环)、叶酸一碳池。因此,胸部神经元特异性过表达引起的转录组变化不如头部明显,且受影响的通路也与之前的结果不同。虽然这些通路不属于典型的长寿通路,但我们认为它们可能参与了过表达果蝇衰老的延迟。