The oxidative stress theory of aging states that aging is associated with a progressive accumulation of reactive oxygen species (ROS). In turn, the build up of free radicals induces physiological dysfunction, irreversible cellular damage, and increased vulnerability to disease. In support of this theory increased levels of free radical species are detected in the brains of patients with age-related neurological disorders such as Alzheimer's disease and Parkinson's disease. Specifically, mitochondria have been extensively studied as a source of age-associated free radicals. The mitochondria theory of aging suggests a positive feedback mechanism where free radicals from mitochondria impair the electron transport chain, inducing mitochondrial impairment and further release of ROS.
Oxidative stress is a condition characterized by elevated levels of intracellular ROS. ROS either are, or break down to form, free radicals. ROS include superoxide anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (OH-) that are capable of reacting with, and damaging DNA, proteins, and lipids. Under normal conditions, ROS are cleared from the cell by the actions of superoxide dismutase, catalase, glutathione peroxidase, thioredoxin, and other molecules. Low levels of intracellular ROS have also been identified as second messengers in signaling pathways and implicated in transcriptional regulation to promote cell proliferation, but higher doses of ROS result in growth arrest and cell death. Bcl-2 inhibits free-radical induced apoptosis. Whether the result is cell survival or apoptosis, oxidative stress activates numerous intracellular signaling pathways such as Akt, NFkB, p53, Jak/Stat, and MAPK to affect changes in gene expression.