Adipose derived mesenchymal stem cells (ADSCs) co-cultured with Epigallocatechin gallate were injected into 20 month aged Wistar rats. Haematoxylin and eosin staining of the cerebral cortex revealed noticeable neurogenic activity and visible improvements in the integrity of the pre frontal cortex tissue compared to ADSC treatment alone. Western blot tests confirmed that ADSCs co-cultured with EGCG enhances cell survival via the p-AKTs473 pathway and improves mitochondrial biogenesis via the SIRT1 pathway while increasing available Brain-derived neurotrophic factor compared to the ADSC group. Furthermore, western blotting shows that EGCG improves the antioxidant activity of the ADSCs in the cortex tissues via the Nrf-2 and HO-1 pathway. However, when miRNA-3575 mimic or inhibitor co-cultured with ADSC was administered, no marked improvements over ADSC alone were detected. Based on these findings, we propose that this variation in EGCG administration combined with stem cell treatment may facilitate functional recovery and enhanced neuroprotection in the aged brain.