Age-related cognitive decline is a growing concern in our ageing population. Emerging evidence suggests that adult hippocampal neurogenesis and synaptogenesis are critical processes in maintaining cognitive function with ageing. We have found that a small percentage (10-15%) of aged wild-type mice (24-month-old), retain youthful cognitive abilities and have confirmed that these mice exhibit substantially higher levels of hippocampal neurogenesis and synapses. This suggests that interventions to promote these pathways may offer protection against cognitive decline. Neurotrophins, such as brain-derived neurotrophic factor (BDNF), promote neuronal survival, neurogenesis, synapse growth, and healthy cognitive function. However, exogenous neurotrophins are unable to cross the blood-brain barrier (BBB), limiting their therapeutic potential. Our lab has recently identified pro-neurotrophic small molecules that can cross the BBB and promote the synthesis of endogenous neurotrophins, thereby enhancing cognitive function. One pro-neurotrophic compound, hericene A, derived from Hericium erinaceus (lion’s mane mushroom), showed great efficacy in vitro and in vivo. We have demonstrated that hericene A promotes neurogenesis in dentate gyrus derived neurospheres and enrichment of neurogenesis associated proteins in human brain organoids. Our data also shows that Hericene A promotes dendritic outgrowth, synaptogenesis and synapse maturation in primary hippocampal neurons and enrichment of synapse and synaptic plasticity associated proteins in human brain organoids. Finally, mouse studies have confirmed that hericene A treatment increases neurotrophic signalling and cognitive performance in vivo. Taken together, these results suggest that pro-neurotrophic molecules such as hericene A are excellent candidates for increasing synaptogenesis and neurogenesis to protect against age-related cognitive decline.