Brain transcriptome changes in the aging Drosophila melanogaster accompany olfactory memory performance deficits

Abstract

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.

Aging mechanisms—A perspective mostly from Drosophila

“…Other aging‐related neurological phenotypes can be also quantified, including brain degeneration vacuoles, 31,41,42 retinal degeneration and loss of ommatidium photoreceptor integrity, 41,42 and neuromuscular junction abnormalities 42,43 . Aging‐related cognitive decline can be assessed by evaluating the fly response to light, olfaction and taste, 44 and memory and learning 45‐47 …”

“…42,43 Aging-related cognitive decline can be assessed by evaluating the fly response to light, olfaction and taste, 44 and memory and learning. [45][46][47] Reproductive decline also occurs during aging and can easily be investigated by quantifying egg-laying or the number of progeny relative to copula copulation. 48,49 Additionally, germ line stem cells can be stained and quantified.…”

Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster

“…Importantly, our recent RNA-seq analysis revealed a significant age-related increase in the expression of the Pdk gene in the heads of old flies and a concomitant decrease in expression of the Mpc1 gene encoding mitochondrial pyruvate carrier [10]. Moreover, two recent transcriptomic studies of the aging fly brain revealed an overall decline in the expression of genes involved in mitochondrial oxidative phosphorylation [46,47]. Taken together, these data provide evidence of decreased pyruvate uptake by agedamaged mitochondria and/or lowered conversion of pyruvate to acetyl-CoA in addition to decreased mitochondrial oxidative phosphorylation in the aging brain.…”

Transcriptome analysis provides genome annotation and expression profiles in the central nervous system ofLymnaea stagnalisat different ages

“…Developmental transcriptomes of well-established invertebrate models such as Caenorhabditis elegans (C. elegans) (Boeck et al, 2016;Lu, Lai, Liao, & Tsai, 2020) and Drosophila melanogaster (D. melanogaster) (Graveley et al, 2011) have been reported. Recent efforts have also focused on the transcriptome of aging D. melanogaster (Moskalev et al, 2019;Pacifico, MacMullen, Walkinshaw, Zhang, & Davis, 2018) and C. elegans (Tarkhov et al, 2019), aiming to reveal molecular mechanisms of longevity or aging trajectories.…”