● Transcriptomic and proteomic responses: Profiling after Humanin exposure in research models to identify pathways downstream of mitochondrial peptide signaling. Concluding PerspectiveHumanin represents a compelling mitochondrial signal peptide with multifaceted potential in research on cellular aging, neurobiology, metabolism, and cellular stress. Humanin peptide suppresses apoptosis by interfering with Bax activation. The mitochondrial-derived peptide humanin activates the ERK1/2, AKT, and STAT3 signaling pathways and has age-dependent signaling differences in the hippocampus. The mitochondrial-derived peptide humanin is a regulator of lifespan and healthspan.