Slowed aging during reproductive dormancy is reflected in genome-wide transcriptome changes in Drosophila melanogaster

Abstract

BackgroundIn models extensively used in studies of aging and extended lifespan, such as C. elegans and Drosophila, adult senescence is regulated by gene networks that are likely to be similar to ones that underlie lifespan extension during dormancy. These include the evolutionarily conserved insulin/IGF, TOR and germ line-signaling pathways. Dormancy, also known as dauer stage in the larval worm or adult diapause in the fly, is triggered by adverse environmental conditions, and results in drastically extended lifespan with negligible senescence. It is furthermore characterized by increased stress resistance and somatic maintenance, developmental arrest and reallocated energy resources. In the fly Drosophila melanogaster adult reproductive diapause is additionally manifested in arrested ovary development, improved immune defense and altered metabolism. However, the molecular mechanisms behind this adaptive lifespan extension are not well understood.ResultsA genome wide analysis of transcript changes in diapausing D. melanogaster revealed a differential regulation of more than 4600 genes. Gene ontology (GO) and KEGG pathway analysis reveal that many of these genes are part of signaling pathways that regulate metabolism, stress responses, detoxification, immunity, protein synthesis and processes during aging. More specifically, gene readouts and detailed mapping of the pathways indicate downregulation of insulin-IGF (IIS), target of rapamycin (TOR) and MAP kinase signaling, whereas Toll-dependent immune signaling, Jun-N-terminal kinase (JNK) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways are upregulated during diapause. Furthermore, we detected transcriptional regulation of a large number of genes specifically associated with aging and longevity.ConclusionsWe find that many affected genes and signal pathways are shared between dormancy, aging and lifespan extension, including IIS, TOR, JAK/STAT and JNK. A substantial fraction of the genes affected by diapause have also been found to alter their expression in response to starvation and cold exposure in D. melanogaster, and the pathways overlap those reported in GO analysis of other invertebrates in dormancy or even hibernating mammals. Our study, thus, shows that D. melanogaster is a genetically tractable model for dormancy in other organisms and effects of dormancy on aging and lifespan.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2383-1) contains supplementary material, which is available to authorized users.

Drosophila insulin-like peptide 1 (DILP1) is transiently expressed during non-feeding stages and reproductive dormancy

“…Adult diapause is characterized by halted reproduction, a drastic reduction of food intake, accompanied by a shift in energy metabolism towards increased nutrient stores, as well as increased stress tolerance, and upregulated immune defense283454. In Drosophila diapause can only be triggered in newly eclosed flies before 10 h of adult life2832.…”

The African turquoise killifish: A research organism to study vertebrate aging and diapause

“…Invertebrate systems have also revealed organismal and genetic links between diapause and aging. First, the individuals that undergo diapause in C. elegans or Drosophila resume a normal lifespan when they reach adulthood (Klass & Hirsh, 1976; Kucerova et al., 2016; Zhao et al., 2016). In other documented examples of insects, individuals that have been through diapause significantly even outlive their counterparts that have never entered diapause (Tatar & Yin, 2001).…”

Characterization of Reproductive Dormancy in Male Drosophila melanogaster

“…Our investigation of female flies suggested that AKH signaling is upregulated and insulin signaling downregulated during dormancy (Kucerová et al, 2016). In the present study we did not detect a significant increase in Akh mRNA expression, but after recovery the levels dropped significantly (Figure 5A).…”

“…Adult dormancy in insects is manifested as an arrest of reproduction, accompanied by decreased food ingestion, suppressed metabolism, increased stress resistance, and extended adult lifespan (Tauber et al, 1986; Tatar and Yin, 2001; Denlinger, 2002; Hahn and Denlinger, 2011; Kubrak et al, 2014; Reis et al, 2015). Hence, adult diapause is highly interesting for identifying gene networks involved in adult senescence and increased longevity (see Tatar and Yin, 2001; Kucerová et al, 2016). …”

“…We have recently investigated experimentally induced reproductive dormancy in female Drosophila melanogaster ( Canton S strain) and established its physiological characteristics as well as genome wide effects on the transcriptome (Kubrak et al, 2014; Kucerová et al, 2016). Although the dormancy in laboratory strains of D. melanogaster does not qualify as a diapause in the strict sense of being induced in advance of poor environmental conditions, rather than being triggered by them (Tauber et al, 1986), we could demonstrate that D. melanogaster is nevertheless a genetically tractable model for dormancy and lifespan extension in other organisms.…”