Aging is associated with a reduction of brain plasticity and learning ability. Using a translational approach with investigations on animals, and on human subjects we investigate whether and how plasticity in the aged brain can be preserved. For this purpose, we use different approaches (telomere length, transcriptomic profile, MRI brainage score, neuropsychological parameters) to determine the biological age of subjects. Aging experiments with rodents show that prenatal stress induces an epigenetic alteration of the stress axis which enhances the inflammation level in the brain. Likewise, strong intermittent inflammatory disorders accelerate brain aging. Antiinflammtory drugs may partially reverse the age-associated disturbances of brain plasticity. Similarly, enriched environment partially re-juvenates the transcriptomic profile of the brain. Based on these observations we currently investigate the role of brain microglia for brain ageing. In the presentation, the methodological approach as well as results from several studies which address interventions to reduce the age-associated decline in brain plasticity will be presented.