Chemically reactive molecules derived from molecular oxygen, including superoxide (O₂⁻), hydrogen peroxide (H₂O₂), and hydroxyl radicals (·OH). ROS are natural byproducts of mitochondrial energy production and serve essential roles in cell signaling and immune defense at controlled levels.

Problems arise when ROS production overwhelms antioxidant defenses—a state called oxidative stress. Excess ROS damage cell membranes, denature proteins, and cause DNA mutations. Mitochondria are both the primary source and primary target of ROS, creating a vicious cycle that accelerates with age. This mitochondrial ROS theory underpins the proposed mechanisms of several longevity-targeted peptides, particularly SS-31, which localizes to the inner mitochondrial membrane specifically to interrupt this cycle.