This study investigates the effects of young blood on age-related cognitive impairments in mice. The researchers used a technique called heterochronic parabiosis, where the circulatory systems of young and aged mice are connected, to show that exposure to young blood can reverse age-related impairments in cognitive function and synaptic plasticity. Microarray analysis of the hippocampus in these mice revealed transcriptional changes related to synaptic plasticity. Immunohistochemistry and Golgi staining confirmed increased dendritic spine density and improved synaptic plasticity in the aged hippocampus. Behavioral tests demonstrated that systemic administration of young blood plasma improved age-related cognitive abilities in both contextual fear conditioning and spatial learning and memory tasks. Mechanistically, the study found that activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus mediates these enhancements. The findings suggest that exposure to young blood can rejuvenate synaptic plasticity and improve cognitive function in aged mice.This study investigates the effects of young blood on age-related cognitive impairments in mice. The researchers used a technique called heterochronic parabiosis, where the circulatory systems of young and aged mice are connected, to show that exposure to young blood can reverse age-related impairments in cognitive function and synaptic plasticity. Microarray analysis of the hippocampus in these mice revealed transcriptional changes related to synaptic plasticity. Immunohistochemistry and Golgi staining confirmed increased dendritic spine density and improved synaptic plasticity in the aged hippocampus. Behavioral tests demonstrated that systemic administration of young blood plasma improved age-related cognitive abilities in both contextual fear conditioning and spatial learning and memory tasks. Mechanistically, the study found that activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus mediates these enhancements. The findings suggest that exposure to young blood can rejuvenate synaptic plasticity and improve cognitive function in aged mice.