Effects of aging on gene expression networks in the Drosophila genetic reference panel

The genetic basis of naturally occurring variation in organismal senescence and lifespan remains largely unknown. We quantified genome-wide gene expression levels of young and 3-week-old flies of the Drosophila Genetic Reference Panel and performed a systems genetics analysis integrating genomic, transcriptomic, and organismal phenotype variation. Aging had widespread but small effects on nearly the entire transcriptome, which were dependent on the genetic background. Although the co-expression module structure was globally robust and largely preserved, connectivity of genes in some pathways decreased with age in both sexes. We mapped expression quantitative trait loci for young and aged flies and found aging led to reduced genetic control of gene expression. The association between gene expression and organismal senescence and lifespan was weak for individual genes but enriched in pathways. This study demonstrates the power of leveraging natural variation and integrative systems genetics analysis to identify genes and pathways related to senescence and aging.