GEOTranscriptomicsDrosophila melanogasterExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322571GEOGSEfalseRapamycin Fly Cell Atlas Reveals Sex-Specific Pro-longevity Impacts at cellular resolutionAging is the dominant risk factor for chronic disease, yet the cell-type–resolved consequences of pro-longevity interventions remain insufficiently defined. Rapamycin, a pharmacological inhibitor of mechanistic target of rapamycin (mTOR) signaling, robustly extends lifespan across taxa and is now being evaluated in human clinical studies. However, how its benefits and liabilities are distributed across distinct cell types in a whole organism is still unclear. Here, we introduce the Rapamycin pro-longevity Fly Cell Atlas (Rapa-FCA), generated using whole-organism single-nucleus transcriptomic profiling in Drosophila melanogaster. Rapamycin elicits the most pronounced transcriptional remodeling in the reproductive system, adipose- and hepatocyte-like metabolic cells, and muscle, whereas neuronal populations show comparatively modest responses. Notably, rapamycin modulates male and female cell types and associated functions in a sex-dependent manner, including effects on reproductive tissues and the neuromuscular junction. We further identify a convergent aging trajectory (CAT) shared across multiple cell types, characterized by elevated mTOR activity, and show that rapamycin suppresses CAT-associated cell states more strongly in females than in males. Finally, we develop cell type–specific aging clock models that uncover divergent geroprotective outcomes between sexes. Collectively, Rapa-FCA provides an organism-wide, sex-resolved cellular map of rapamycin action, delineating tissue-specific benefits and vulnerabilities and informing opportunities for precision longevity interventions.2026/06/02GSE322571GSM9555090GSM9555091GSM9555092GSM9555093GSM9555094GSM9555095GSM9555096GSM9555097GSM9555098GSM9555099GSM9555082GSM9555083GSM9555084GSM9555085GSM9555086GSM9555087GSM9555088GSM9555100GSM9555089GSM9555101GSM9555102GSM9555103GSM9555104GSM9555105GSM9555106GSM9555107GSM9555108GSM955510934457322571Drosophila melanogaster