Department of Neuroscience, The Scripps Research Institute-Florida, Jupiter, Florida, United States of America.
PLoS One. 2018 Dec 21;13(12):e0209405. doi: 10.1371/journal.pone.0209405. eCollection 2018.
Cognitive decline is a common occurrence of the natural aging process in animals and studying age-related changes in gene expression in the brain might shed light on disrupted molecular pathways that play a role in this decline. The fruit fly is a useful neurobiological model for studying aging due to its short generational time and relatively small brain size. We investigated age-dependent changes in the Drosophila melanogaster whole-brain transcriptome by comparing 5-, 20-, 30- and 40-day-old flies of both sexes. We used RNA-Sequencing of dissected brain samples followed by differential expression, temporal clustering, co-expression network and gene ontology enrichment analyses. We found an overall decline in expression of genes from the mitochondrial oxidative phosphorylation pathway that occurred as part of aging. We also detected, in females, a pattern of continuously declining expression for many neuronal function genes, which was unexpectedly reversed later in life. This group of genes was highly enriched in memory-impairing genes previously identified through an RNAi screen. We also identified deficits in short-term olfactory memory performance in older flies of both sexes, some of which matched the timing of certain changes in the brain transcriptome. Our study provides the first transcriptome profile of aging brains from fruit flies of both sexes, and it will serve as an important resource for those who study aging and cognitive decline in this model.
认知能力下降是动物自然衰老过程中的常见现象，研究大脑中与年龄相关的基因表达变化可能有助于揭示在这一下降过程中起作用的分子途径的紊乱。果蝇由于其较短的世代时间和相对较小的大脑体积，是研究衰老的有用神经生物学模型。我们通过比较 5 天、20 天、30 天和 40 天龄的雌雄果蝇，研究了果蝇全脑转录组随年龄的变化。我们使用了对分离的脑组织样本进行 RNA 测序，然后进行差异表达、时间聚类、共表达网络和基因本体富集分析。我们发现，参与衰老过程的线粒体氧化磷酸化途径的基因表达总体下降。我们还在雌性果蝇中发现了许多神经元功能基因的连续表达下降模式，这一模式在生命后期出乎意料地逆转。这组基因在通过 RNAi 筛选鉴定的记忆损伤基因中高度富集。我们还发现，雌雄果蝇的短期嗅觉记忆能力都有缺陷，其中一些与大脑转录组的某些变化时间相匹配。我们的研究提供了来自雌雄果蝇衰老大脑的首个转录组图谱，它将成为那些在该模型中研究衰老和认知能力下降的人的重要资源。
