Ageing is the primary risk factor for multiple neurodegenerative disorders. Cellular ageing is, however, malleable: When combining the Yamanaka factors (Oct4, Sox2, Klf4, c-Myc; OSKM) in careful moderation through a technique called partial reprogramming, cells can be reprogrammed into an epigenetically younger state without losing their initial identity and function. In mice, partial reprogramming improves age-related memory decline, although the mechanisms behind this improvement are still unknown. Although partial reprogramming is likely too invasive for human use, the technique can still be used to study rejuvenation mechanisms. Astrocytes are among the earliest and most affected brain cells by ageing and are integral in maintaining brain homeostasis. With ageing, astrocyte functions become impaired, contributing to neurological decline, and make the brain vulnerable to pathology. However, if rejuvenated, this ageing astrocyte phenotype may be reversed and may potentially improve the health of other neural cells. Here, we use mass spectrometry to study protein changes following partial reprogramming in 5- and 15-months-old mice. Immunohistochemistry was performed to confirm cell-specificity of the astrocyte-specific Gfap TurboID adeno-associated virus (AAV), used to perform astrocyte-specific proteomics, with linear mixed effects models used for immunohistochemical quantification statistics (Gfap TurboID AAV, N = 7-8 mice; no-AAV control, N = 3 mice). Using differential expression and Rank–Rank Hypergeometric Overlap analyses, we compared proteomic changes happening with ageing (5-months (N = 6) vs 15-months (N = 8) and with partial reprogramming (15-month-old partially reprogramed mice (N = 7) vs age-matched controls (N = 8)). Preliminary results indicate that several proteins upregulated with ageing show reduced expression following partial reprogramming, suggesting a shift in the astrocyte proteome consistent with a more youthful state. Further analyses and experiments will aim to identify the pathways and mechanisms involved which may inform future strategies for neuroprotective therapies. All animal work was carried out in accordance with UK Home Office regulations.