Aging is the single greatest risk factor for neurodegenerative disease. Mitophagy safeguards cellular and tissue health by selectively eliminating damaged mitochondria. Mitophagy declines with age in short-lived model organisms, yet its physiological regulation in the aging mammalian brain and its relationship to other autophagy pathways remain poorly defined. I will present new insights into the spatiotemporal dynamics of mitophagy in the aging mammalian brain. Using high resolution spatiocellular mapping of genetically encoded optical reporter mice (mito-QC and auto-QC), our in vivo analyses reveal striking subset-specific dynamics in both mitophagy and macroautophagy across intact brain circuits. I will present these previously unrecognized age dependent trajectories, with a particular focus on inflection points in midlife, newly identified sites of mitophagy activity in clinically relevant and underexplored neural circuits and neuroimmune cellular subsets. I will also highlight emerging evidence of age-related endolysosomal dysfunction in the healthy mammalian brain, a mechanism further exacerbated in preclinical neurodegeneration. Together with emerging human data, our findings uncover spatiotemporally defined autophagy dynamics in the aging nervous system. I will also present our ongoing efforts to understand healthy brain aging in unconventional long-lived model systems. Our work provides a foundational resource to guide the development of precision therapeutic strategies targeting mitophagy in neurology