Updated project metadata. Aging manifests as progressive deterioration in cellular and systemic homeostasis, requiring systems-level perspectives to understand the gradual molecular dysregulation of underlying biological processes. Here, we collected data for the analysis of systems-level changes in the molecular regulation of biological processes under multiple lifespan-extending interventions in mice. High-resolution shotgun LC-MS/MS data were collected from liver samples obtained from multiple mouse cohorts treated with different lifespan-extending drugs, and analyzed using reverse phase liquid chromatography on Orbitrap mass spectrometers.