Mitochondrial oxidative stress in aging and healthspan

Mitochondrial free radical theory of aging proposes that the primary driver of the aging process is free radical-induced oxidative damage which accumulates within mitochondria over time. This theory remains controversial, as several studies have shown either supporting confirmation of it or opposing data against it. Furthermore, recent evidence has shown the crucial roles of reactive oxygen species (ROS) in cellular signaling and mitochondrial hormesis. This chapter will discuss the evidence supporting mitochondrial free radical theory, especially the studies applying mice overexpressing catalase targeted to mitochondria (mCAT) and how this can be reconciled with mitochondrial hormesis. The relationship of ROS and mitochondrial protein quality control mechanisms, including autophagy, ubiquitin-proteasome system, and mitochondrial dynamics in the context of aging will be reviewed. As healthspans have become more important in the field of aging research, the role of mitochondrial oxidative stress in various age-related diseases are discussed, including cardiometabolic diseases, neurodegenerative diseases, skeletal muscle dysfunction, and cancer. Finally, potential antiaging strategies are reviewed in relationship to ROS and autophagy.