Author
William C. Orr
Other affiliations: Methodist University, Emek Medical Center, Southern Methodist University
Bio: William C. Orr is an academic researcher from University of Oklahoma Health Sciences Center. The author has contributed to research in topics: Oxidative stress & GERD. The author has an hindex of 52, co-authored 166 publications receiving 10049 citations. Previous affiliations of William C. Orr include Methodist University & Emek Medical Center.
Topics: Oxidative stress, GERD, Superoxide dismutase, Catalase, Heartburn
Papers published on a yearly basis
Papers
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TL;DR: A study of the effects of simultaneous overexpression of copper-zinc superoxide dismutase and catalase provides direct support for the free radical hypothesis of aging.
Abstract: The hypothesis that oxygen free radicals are causally involved in the aging process was tested by a study of the effects of simultaneous overexpression of copper-zinc superoxide dismutase and catalase. As compared to diploid controls, transgenic flies carrying three copies of each of these genes exhibited as much as a one-third extension of life-span, a longer mortality rate doubling time, a lower amount of protein oxidative damage, and a delayed loss in physical performance. Results provide direct support for the free radical hypothesis of aging.
1,470 citations
TL;DR: A critical overview of the currently available evidence bearing on the validity of the oxidative stress hypothesis of aging can be found in this paper, where the authors conclude that although there is considerable evidence implicating oxidative stress in the aging process, additional evidence is needed to clearly define the nature of the involvement.
614 citations
TL;DR: The main objective of this review is to examine the role of endogenous reactive oxygen/nitrogen species (ROS) in the aging process and proposes the "redox stress hypothesis", which proposes that aging-associated functional losses are primarily caused by a progressive pro-oxidizing shift in the redox state of the cells, which leads to the overoxidation of redox-sensitive protein thiols and the consequent disruption of theredox-regulated signaling mechanisms.
425 citations
TL;DR: Under the organizational aegis of Project Sleep and the Association of Sleep Disorders Centers (ASDC), nearly 5,000 patient records from 11 sleep-wake disorders clinics were analyzed in a cooperative study, and the most prevalent diagnoses were sleep apnea and narcolepsy.
Abstract: Under the organizational aegis of Project Sleep and the Association of Sleep Disorders Centers (ASDC), nearly 5,000 patient records from 11 sleep-wake disorders clinics were analyzed in a cooperative study. These cases represented the diagnostic experience of each of these centers over a two-year period. Each patient underwent polysomnographic study, and his or her condition was diagnosed according to the ASDC classification system, a new, standardized nosology of sleep disorders medicine. The most common major diagnostic category was "disorders of excessive sleepiness (hypersomnia)," 42%; this was followed by "disorders of initiating and maintaining sleep (insomnia)," 26%; "penile tumescence evaluations for impotency," 17%; "parasomnias," 3%; and "disorders of the sleep-wake schedule," 2%. If the impotency evaluations performed in the sleep clinics are removed from the total, leaving only the population that was studied because of sleep complaints, the proportions of the diagnostic categories are hypersomnia, 51%; insomnia, 31%; parasomnias, 15%; and sleep-wake schedule disturbances, 3%. The most prevalent diagnoses in the hypersomnia category were sleep apnea (43%) and narcolepsy (25%). Psychiatric disorders (35%) comprised the most frequent group of insomnia diagnoses, though a variety of other disorders were common. The applications of these results for the practicing physician are discussed. ( JAMA 1982;247:997-1003)
352 citations
TL;DR: Exposure of flies to sublethal hyperoxia irreversibly enhanced the carbonyl content of the flies and decreased their rate of oxygen consumption and support the general concept that oxidative stress may be a causal factor in the aging process.
Abstract: The objective of this study was to test some of the predictions of the oxidative-stress hypothesis of aging, which postulates that aging is causally associated with the molecular damage inflicted by reactive oxygen species. Protein carbonyl content was used as an index of molecular oxidative modifications. The carbonyl content was found to be associated with the physiological age or life expectancy of flies rather than with their chronological age. Exposure of flies to sublethal hyperoxia (100% oxygen) irreversibly enhanced the carbonyl content of the flies and decreased their rate of oxygen consumption. Results of this study indicate that protein carbonyl content may be a biomarker of aging and support the general concept that oxidative stress may be a causal factor in the aging process.
335 citations
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TL;DR: There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
Abstract: At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...
9,131 citations
TL;DR: Evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span is reviewed.
Abstract: Living in an oxygenated environment has required the evolution of effective cellular strategies to detect and detoxify metabolites of molecular oxygen known as reactive oxygen species. Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span.
8,665 citations
01 Jun 2000
TL;DR: Evidence for plant stress signaling systems is summarized, some of which have components analogous to those that regulate osmotic stress responses of yeast, some that presumably function in intercellular coordination or regulation of effector genes in a cell-/tissue-specific context required for tolerance of plants.
Abstract: ▪ Abstract Plant responses to salinity stress are reviewed with emphasis on molecular mechanisms of signal transduction and on the physiological consequences of altered gene expression that affect biochemical reactions downstream of stress sensing. We make extensive use of comparisons with model organisms, halophytic plants, and yeast, which provide a paradigm for many responses to salinity exhibited by stress-sensitive plants. Among biochemical responses, we emphasize osmolyte biosynthesis and function, water flux control, and membrane transport of ions for maintenance and re-establishment of homeostasis. The advances in understanding the effectiveness of stress responses, and distinctions between pathology and adaptive advantage, are increasingly based on transgenic plant and mutant analyses, in particular the analysis of Arabidopsis mutants defective in elements of stress signal transduction pathways. We summarize evidence for plant stress signaling systems, some of which have components analogous to t...
4,596 citations
TL;DR: It is argued that redox biology, rather than oxidative stress, underlies physiological and pathological conditions.
4,297 citations
TL;DR: This review describes the main mitochondrial sources of reactive species and the antioxidant defences that evolved to prevent oxidative damage in all the mitochondrial compartments and discusses various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants.
Abstract: The reduction of oxygen to water proceeds via one electron at a time. In the mitochondrial respiratory chain, Complex IV (cytochrome oxidase) retains all partially reduced intermediates until full reduction is achieved. Other redox centres in the electron transport chain, however, may leak electrons to oxygen, partially reducing this molecule to superoxide anion (O2−•). Even though O2−• is not a strong oxidant, it is a precursor of most other reactive oxygen species, and it also becomes involved in the propagation of oxidative chain reactions. Despite the presence of various antioxidant defences, the mitochondrion appears to be the main intracellular source of these oxidants. This review describes the main mitochondrial sources of reactive species and the antioxidant defences that evolved to prevent oxidative damage in all the mitochondrial compartments. We also discuss various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants.
4,282 citations