Age-related increase of oxidative stress-induced apoptosis in mice - Prevention by Ginkgo biloba extract (EGb761)

Enhanced apoptosis and elevated levels of reactive oxygen species (ROS) pla y a major role in aging. In addition, several neurodegenerative diseases ar e associated with increased oxidative stress and apoptosis in neuronal tiss ue. Antioxidative treatment has neuro-protective effects. The aim of the pr esent study was to evaluate changes of susceptibility to apoptotic cell dea th by oxidative stress in aging and its inhibition by the antioxidant Ginkg o biloba extract EGb761. We investigated basal and ROS-induced levels of ap optotic lymphocytes derived from the spleen in young (3 months) and old (24 months) mice. ROS were induced by 2-deoxy-D-ribose (dRib) that depletes th e intracellular pool of reduced glutathione. Lymphocytes from aged mice acc umulate apoptotic cells to a significantly higher extent under basal condit ions compared to cells from young mice. Treatment with dRib enhanced this d ifference, implicating a higher sensitivity to ROS in aging. Apoptosis can be reduced in vitro by treatment with EGb761. In addition, mice were treate d daily with 100mg/kg EGb761 per os over a period of two weeks. ROS-induced apoptosis was significantly reduced in the EGb761 group. Interestingly, th is effect seemed to be more pronounced in old mice.