<p>The comparative biology of aging leverages the remarkable diversity in aging rates and lifespans across species to uncover naturally evolved adaptations that promote longevity, disease resistance and injury resilience. The beauty of comparative biology is that it discovers adaptations that evolved outside of the protected laboratory environment, shaped by natural selection under real-world pressures. In this Review, we outline key approaches in comparative biology of aging studies, including the study of public mechanisms, which are shared between species, and private mechanisms, which are species-specific. Additionally, we present insights gained through high-throughput omics technologies—including genomics, transcriptomics, epigenomics, proteomics and metabolomics—and illustrate how these findings advance our understanding of how to ameliorate the hallmarks of aging, enhance cancer resistance and improve regeneration, with a focus on mammals. Finally, we offer practical guidance for designing and interpreting comparative studies aimed at understanding and translating longevity mechanisms.</p>