Dying occurs as a defined molecular progression in Drosophila rather than as nonspecific physiological collapse.

While we know much about aging, dying remains mysterious. Here, we show that old-age death in Drosophila is an orderly process that follows, but is distinguishable from, aging itself. We apply pseudotime trajectory analysis to transcriptomic data from individual flies as they approach death. This uncovers a reproducible progression of molecular events that accompany dying, as revealed by systematic changes in gene expression, including both continuation of some processes of early- and mid-life aging, but also activation of processes that are not associated with aging but instead define progression toward death. Finally, we reanalyze an existing Caenorhabditis elegans dataset and find that many processes we observe in dying flies also vary among dying worms, suggesting that features of dying have been maintained across 600 Myr of evolution. These data challenge the idea that dying is simply a collapse of physiology that is the inherent conclusion to the dysfunctions of aging.