Multiomic Analysis of Adult Diapause in Drosophila melanogaster Identifies Hallmarks of Cellular Quiescence

Age is a fundamental aspect of biology that underlies the efficacy of a broad range of functions. Identifying determinants for how quickly or slowly we age will contribute greatly to our understanding of age as a modifier of overall health, particularly to the advancement of therapeutic interventions designed to mitigate or delay age-associated disorders. While much work has been devoted to the study of genetic or pharmacological interventions that extend lifespan, this approach does not necessarily recapitulate the physiological profile of naturally long-lived individuals. Diapause and diapause-like states constitute natural, inducible and evolutionarily conserved examples of lifespan plasticity that are well-suited to serve as physiologically accurate models of longevity. Here, we leveraged a metabolically critical signaling organ in Drosophila, the fat body, to examine diapause-associated transcription in the context of chromatin accessibility and the regulation of lifespan. Through a combination of ATAC-seq and RNA-seq, our observations suggest chromatin is globally reorganized in diapause and may assume a poised conformation to facilitate the rapid transcription of pro-development genes upon diapause termination. We found particular significance of GAF, NELF, and RNA polymerase III in this context. Congruently, transcription during diapause appears to favor many processes supporting the maintenance of cellular quiescence and the inhibition of differentiation. Our data are consistent with a model wherein diapause induces cellular quiescence in the fat body, as was additionally supported through fluorescent microscopy and comparison with public ChIP-seq data for developmentally juvenile files. This work opens the possibility that longevity in diapause may be partially determined through a lack of mitogenic signaling from the quiescent niche, concurrent with changes to the hormonal and immunological profiles that skew metabolism towards tissue maintenance. ### Competing Interest Statement The authors have declared no competing interest.