Oxidative damage hypothesis of stress-associated aging acceleration: neuroprotective effects of natural and nutritional antioxidants

We propose that stress may contribute to aging acceleration and age-associated degenerative disease by generating oxidants in the mitochondria, causing oxidative damage to lipids, proteins, and nucleic acids, weakening antioxidant defense systems, and further affecting the homeostasis of numerous mediators of defense reactions including hormones, neurotransmitters, and immune cytokines, all of which, like oxidants, are dangerous in excess. Natural and nutritional antioxidant administration might be an effective strategy to fight against stress and stress-associated aging acceleration and degenerative diseases by enhancing antioxidant defense system, scavenging oxidants, inhibiting oxidative damage, and regulating all mediators well balanced. We reviewed the recent evidence of stress-induced oxidative damage by different stress models in different organs, especially in the brain, and also summarized the neuroprotective effects of natural and nutritional anti-stress antioxidants, including vitamins A, C, E, estrogen, dehydroepiandrosterone, glutathione, acetyl-carnitine, and some herbal extracts.