Mitochondrial Dysfunction as a Key Event during Aging: From Synaptic Failure to Memory Loss

Abstract

Mitochondria are important cellular organelles with key regulatory functions in energy production, oxidative balance, and calcium homeostasis. This is especially important in the brain, since neurons require a large number of functional mitochondria to supply their high energy requirement, mainly for synaptic processes. A decrease in the activity and quality of mitochondria in the brain, particularly in the hippocampus, is associated with normal aging and a large number of neurodegenerative diseases compromising memory function. Although synaptic and cognitive dysfunction is multifactorial, growing evidence demonstrates that mitochondria play a key role in these processes and suggests that maintaining mitochondrial function could prevent these age-dependent alterations. In this chapter, we will discuss the hippocampal mitochondrial dysfunction present in aging and how these defects promote age-associated synaptic damage and cognitive impairment. We will summarize evidence that shows how neurodegeneration can be accelerated or attenuated during aging by modulating mitochondrial function.