The article reviews the role of oxidative damage in the aging process, focusing on mitochondrial dysfunction. It argues that endogenously produced oxidants, primarily generated by mitochondria, are the major source of oxidative lesions that accumulate with age. Several mitochondrial functions decline with age, including proton leakage, membrane fluidity, and cardiolipin levels, which support the function of inner mitochondrial membrane proteins. Acetyl-L-carnitine, a high-energy mitochondrial substrate, has been shown to reverse many age-associated deficits in cellular function by increasing ATP production. The accumulation of oxidative damage to mitochondrial DNA and proteins is proposed to contribute significantly to cellular, tissue, and organismal aging. The article also discusses species-specific differences in longevity and the role of mitochondrial proton leakage in oxidant production. Additionally, it explores the effects of calorie restriction on mitochondrial function and oxidant production, and the impact of mitochondrial dysfunction on neuronal and immune system aging.The article reviews the role of oxidative damage in the aging process, focusing on mitochondrial dysfunction. It argues that endogenously produced oxidants, primarily generated by mitochondria, are the major source of oxidative lesions that accumulate with age. Several mitochondrial functions decline with age, including proton leakage, membrane fluidity, and cardiolipin levels, which support the function of inner mitochondrial membrane proteins. Acetyl-L-carnitine, a high-energy mitochondrial substrate, has been shown to reverse many age-associated deficits in cellular function by increasing ATP production. The accumulation of oxidative damage to mitochondrial DNA and proteins is proposed to contribute significantly to cellular, tissue, and organismal aging. The article also discusses species-specific differences in longevity and the role of mitochondrial proton leakage in oxidant production. Additionally, it explores the effects of calorie restriction on mitochondrial function and oxidant production, and the impact of mitochondrial dysfunction on neuronal and immune system aging.