title: The essential requirement for superoxide radical and nitric oxide formation for normal physiological function and healthy aging.
abstract: Contrary to the dogma that superoxide anion and hydrogen peroxide formation are highly deleterious to cell function and healthy aging, we suggest this premise is flawed. Superoxide anion and hydrogen peroxide formation are essential to normal cellular function; they constitute a second messenger system absolutely required for the regulation of the metabolome. Embraced within this regulation is the modulation of cellular redox poise, bioenergy output, gene expression and cell differentiation. A key component in the overall process is coenzyme Q10 whose prooxidant function through the formation of superoxide anion and hydrogen peroxide is a major factor in the overall processes. The free radical gas, nitric oxide (similarly to superoxide anion), functions in the regulation of a wide range of cell systems. As part of the normal physiological process, superoxide anion and NO function separately and interactively as second messengers. Superoxide anion and nitric oxide play an intrinsic role in the regulated ordered turnover of proteins, rather than randomly cause protein damage and their inactivation. The proposition that metabolic free radical formation is unequivocally deleterious to cell function is rebutted; their toxicity as primary effectors in the aging process has been overemphasized. The concept that a dietary supplement of high concentrations of small-molecule antioxidants is a prophylactic/amelioration therapy for the aging process and age-associated diseases is questioned as to its clinical validity.
authors.affiliation: Centre for Molecular Biology and Medicine, Epworth Medical Centre, Richmond, Melbourne, Vic. 3121, Australia. tlinnane@cmbm.com.au
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Linnane
authors.forename: Michael
authors.initials: M
authors.lastname: Kios
authors.forename: Luis
authors.initials: L
authors.lastname: Vitetta
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use; D002454:Cell Differentiation / Q000502:physiology; D003067:Coenzymes / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D013482:Superoxide Dismutase / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000502:physiology
chemical_list: D000975:Antioxidants; D003067:Coenzymes; D011506:Proteins; D013481:Superoxides; D014451:Ubiquinone; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; C024989:coenzyme Q10