Aims: Mitochondrial damage is neutralised by mitophagy, thereby preventing cellular dysfunction and apoptosis. Mitophagy is the selective autophagy of mitochondria and has long been linked to age-dependent neurodegenerative disorders, including Parkinson’s and Alzheimer’s disease. . In cell-based systems and short-lived model organisms, mitophagy declines with age. However, the trajectories of mitophagy within the aging mammalian brain remain unexplored. We profiled mitophagy and macroautophagy within intact brain tissues using advanced genetically-encoded optical reporter mice. Methods: We analysed physiological mitophagy and macroautophagy, respectively, in brain tissues from longitudinal cohorts of mito-QC and auto-QC reporter mice, which have been extensively characterised. We used high resolution confocal microscopy, transmission electron microscopy and quantitative cell biology. Results: During natural aging, we observed significant changes in mitophagy and macroautophagy in the mammalian nervous system. We used longitudinal quantitative profiling of mitophagy and autophagy reporter mice cohorts from young (3 months) to geriatric (<26 months) to identify cell and region-specific alterations in cargo turnover between distinct populations of neurons and non-neuronal cells. Additionally, we observed age-dependent remodelling and dysfunction of the endolysosomal network. Conclusions: Our findings establish a new landscape of in vivo selective and non-selective autophagy through neural space and time. This comprehensive resource reveals a new understanding of mitophagy in vivo and will aid the pre-clinical phenotyping of precision therapeutic strategies to target age-related mitochondrial dysfunction in the CNS.