The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. In this issue, Zhang et al. (page number 718–734) presented the first single-nucleus transcriptomic atlas of primate hippocampal aging. They revealed impaired progenitor cell division and compromised neuronal function along the neurogenesis trajectory, as well as elevated pro-inflammatory responses in the niche cells contributing to a hostile microenvironment in the aged hippocampus. Consistently, they observed a variety of new aging-associated phenotypic changes, including increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. This may provide potential diagnostic biomarkers and therapeutic interventions against the agerelated neurodegenerative diseases.