Rapamycin Fly Cell Atlas Reveals Sex-Specific Pro-longevity Impacts at cellular resolution

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.