One of the areas of the brain most affected by aging is the hippocampus, a crucial structure in learning and memory processes. My laboratory studies the changes that hippocampal mitochondria undergo in aging, specifically those found in synapses, which correspond to areas of neuronal communication. Synaptic mitochondria are more vulnerable to damage than nonsynaptic mitochondria. We are investigating structural and functional differences in synaptic mitochondria that explain this vulnerability and their contribution to age related memory loss, with particular emphasis on the mitochondrial protease Lonp1. We also study factors that promote mitochondrial dysfunction, including the accumulation of phosphorylated tau (Ser396-Ser404: PHF-1) in mitochondria, a microtubule-associated protein that, upon phosphorylation, loses its function. Another aspect that we explore is the possible antiaging effect of molecules that improve mitochondrial function. We use in vitro and in vivo models, including primary mouse hippocampal neuron cultures, organotypic cultures, and the accelerated senescence-prone or normally aged mouse (SAMP8).