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  • 1
    Online-Ressource
    Online-Ressource
    American Physiological Society ; 1998
    In:  Physiological Reviews Vol. 78, No. 2 ( 1998-04-01), p. 547-581
    In: Physiological Reviews, American Physiological Society, Vol. 78, No. 2 ( 1998-04-01), p. 547-581
    Kurzfassung: Beckman, Kenneth B., and Bruce N. Ames. The Free Radical Theory of Aging Matures. Physiol. Rev. 78: 547–581, 1998. — The free radical theory of aging, conceived in 1956, has turned 40 and is rapidly attracting the interest of the mainstream of biological research. From its origins in radiation biology, through a decade or so of dormancy and two decades of steady phenomenological research, it has attracted an increasing number of scientists from an expanding circle of fields. During the past decade, several lines of evidence have convinced a number of scientists that oxidants play an important role in aging. (For the sake of simplicity, we use the term oxidant to refer to all “reactive oxygen species,” including O − 2 ⋅, H 2 O 2 , and ⋅OH, even though the former often acts as a reductant and produces oxidants indirectly.) The pace and scope of research in the last few years have been particularly impressive and diverse. The only disadvantage of the current intellectual ferment is the difficulty in digesting the literature. Therefore, we have systematically reviewed the status of the free radical theory, by categorizing the literature in terms of the various types of experiments that have been performed. These include phenomenological measurements of age-associated oxidative stress, interspecies comparisons, dietary restriction, the manipulation of metabolic activity and oxygen tension, treatment with dietary and pharmacological antioxidants, in vitro senescence, classical and population genetics, molecular genetics, transgenic organisms, the study of human diseases of aging, epidemiological studies, and the ongoing elucidation of the role of active oxygen in biology.
    Materialart: Online-Ressource
    ISSN: 0031-9333 , 1522-1210
    RVK:
    Sprache: Englisch
    Verlag: American Physiological Society
    Publikationsdatum: 1998
    ZDB Id: 1471693-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    American Chemical Society (ACS) ; 1998
    In:  The Journal of Physical Chemistry A Vol. 102, No. 12 ( 1998-03-01), p. 2231-2236
    In: The Journal of Physical Chemistry A, American Chemical Society (ACS), Vol. 102, No. 12 ( 1998-03-01), p. 2231-2236
    Materialart: Online-Ressource
    ISSN: 1089-5639 , 1520-5215
    RVK:
    Sprache: Englisch
    Verlag: American Chemical Society (ACS)
    Publikationsdatum: 1998
    ZDB Id: 2006031-2
    ZDB Id: 1357795-5
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  • 3
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    Wiley ; 1998
    In:  Annals of the New York Academy of Sciences Vol. 854, No. 1 ( 1998-11), p. 118-127
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 854, No. 1 ( 1998-11), p. 118-127
    Kurzfassung: ABSTRACT: Interest in the role of mitochondria in aging has intensified in recent years. This focus on mitochondria originated in part from the free radical theory of aging, which argues that oxidative damage plays a key role in degenerative senescence. Among the numerous mechanisms known to generate oxidants, leakage of the superoxide anion and hydrogen peroxide from the mitochondrial electron transport chain are of particular interest, due to the correlation between species‐specific metabolic rate (“rate of living”) and life span. Phenomenological studies of mitochondrial function long ago noted a decline in mitochondrial function with age, and on‐going research continues to add to this body of knowledge. The extranuclear somatic mutation theory of aging proposes that the accumulation of mutations in the mitochondrial genome may be responsible in part for the mitochondrial phenomenology of aging. Recent studies of mitochondrial DNA (mtDNA) deletions have shown that they increase with age in humans and other mammals. Currently, there exist numerous important and fundamental questions surrounding mitochondria and aging. Among these are (1) How important are mitochondrial oxidants in determining overall cellular oxidative stress? (2) What are the mechanisms of mitochondrial oxidant generation? (3) How are lesions and mutations in mtDNA formed? (4) How important are mtDNA lesions and mutations in causing mitochondrial dysfunction? (5) How are mitochondria regulated, and how does this regulation change during aging? (6) What are the dynamics of mitochondrial turnover? (7) What is the relationship between mitochondrial damage and lipofuscinogenesis? (8) What are the relationships among mitochondria, apopotosis, and aging? and (9) How can mitochondrial function (ATP generation and the establishment of a membrane potential) and dysfunction (oxidant generation) be modulated and degenerative senescence thereby treated?
    Materialart: Online-Ressource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 1998
    ZDB Id: 2834079-6
    ZDB Id: 211003-9
    ZDB Id: 2071584-5
    SSG: 11
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: European Journal of Cardio-Thoracic Surgery, Oxford University Press (OUP), Vol. 15, No. 1 ( 1999-1), p. 24-30
    Materialart: Online-Ressource
    ISSN: 1873-734X , 1010-7940
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 1999
    ZDB Id: 1500330-9
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  • 5
    Online-Ressource
    Online-Ressource
    Acoustical Society of America (ASA) ; 1995
    In:  The Journal of the Acoustical Society of America Vol. 97, No. 1 ( 1995-01-01), p. 471-490
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 97, No. 1 ( 1995-01-01), p. 471-490
    Kurzfassung: Articulatory and acoustic variability in the production of five American English vowels was examined. The data were movement records for selected fleshpoints on the midsagittal tongue surface, recorded using the x-ray microbeam. An algorithm for nonlinearly transforming fleshpoint positions to a new Cartesian space in which the x and y axes represent, respectively, the distance of the fleshpoint along the opposing vocal tract wall and the distance perpendicular to the tract wall, is described. The transformation facilitates a test of Quantal Theory in which variability in the two dimensions is compared over many productions of a given vowel type. The data provide some support for the theory. For fleshpoints near ‘‘quantal’’ constriction sites, the primary variability was in the x dimension (constriction location). The y-dimension values were more tightly constrained, and the formant frequencies were more significantly correlated with the y values than with the x values. The greater variability in constriction location than in degree was not an artifact of the greater distances traversed in the x dimension between the vowel and constrictions in neighboring consonants, since the pattern was preserved when pellet values were translated to take into account a ‘‘context-free’’ vowel target (the average values in the context of preceding and following labial consonants). Moreover, the observed correlations between formant values and pellet positions in the two dimensions for [i] and [u] were duplicated in an articulatory-to-acoustic modeling test using values for constriction length and cross-sectional area estimated from the data. The model showed smaller second formant variability in the x dimension than in the y dimension for equal-sized excursions near the constriction sites for these close vowels, in keeping with the interpretation that speakers exercise less precise control in just the dimensions and regions where quantal stability is available. However, the articulatory pattern was seen not just in vowels which clearly have consonantlike constrictions (the quantal vowels [i], [u] , and [ɑ ]), but also in nonquantal vowels such as [æ] .
    Materialart: Online-Ressource
    ISSN: 0001-4966 , 1520-8524
    RVK:
    Sprache: Englisch
    Verlag: Acoustical Society of America (ASA)
    Publikationsdatum: 1995
    ZDB Id: 1461063-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Elsevier BV ; 1995
    In:  American Journal of Ophthalmology Vol. 120, No. 4 ( 1995-10), p. 530-531
    In: American Journal of Ophthalmology, Elsevier BV, Vol. 120, No. 4 ( 1995-10), p. 530-531
    Materialart: Online-Ressource
    ISSN: 0002-9394
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1995
    ZDB Id: 2019600-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    Elsevier BV ; 1999
    In:  Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Vol. 424, No. 1-2 ( 1999-3), p. 51-58
    In: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Elsevier BV, Vol. 424, No. 1-2 ( 1999-3), p. 51-58
    Materialart: Online-Ressource
    ISSN: 0027-5107
    RVK:
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1999
    ZDB Id: 1491099-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Elsevier BV ; 1997
    In:  Journal of Biological Chemistry Vol. 272, No. 32 ( 1997-08), p. 19633-19636
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 272, No. 32 ( 1997-08), p. 19633-19636
    Materialart: Online-Ressource
    ISSN: 0021-9258
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1997
    ZDB Id: 2141744-1
    ZDB Id: 1474604-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    In: The American Journal of Cardiology, Elsevier BV, Vol. 80, No. 4 ( 1997-8), p. 458-463
    Materialart: Online-Ressource
    ISSN: 0002-9149
    RVK:
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 1997
    ZDB Id: 2019595-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    Proceedings of the National Academy of Sciences ; 1998
    In:  Proceedings of the National Academy of Sciences Vol. 95, No. 1 ( 1998-01-06), p. 288-293
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 95, No. 1 ( 1998-01-06), p. 288-293
    Kurzfassung: Oxidative DNA damage is important in aging and the degenerative diseases of aging such as cancer. Estimates commonly rely on measurements of 8-oxo-2′-deoxyguanosine (oxo 8 dG), an adduct that occurs in DNA and is also excreted in urine after DNA repair. Here we examine difficulties inherent in the analysis of oxo 8 dG, identify sources of artifacts, and provide solutions to some of the common methodological problems. A frequent criticism has been that phenol in DNA extraction solutions artificially increases the measured level of oxo 8 dG. We found that phenol extraction of DNA contributes a real but minor increase in the level of oxo 8 dG when compared, under equivalent conditions, with a successful nonphenol method. A more significant reduction in the baseline level was achieved with a modification of the recently introduced chaotropic NaI method, reducing our estimate of the level of steady-state oxidative adducts by an order of magnitude to 24,000 adducts per cell in young rats and 66,000 adducts per cell in old rats. Of several alternative methods tested, the use of this chaotropic technique of DNA isolation by using NaI produced the lowest and least variable oxo 8 dG values. In further studies we show that human urinary 8-oxo-guanine (oxo 8 Gua) excretion is not affected by the administration of allopurinol, suggesting that, unlike some methylated adducts, oxo 8 Gua is not derived enzymatically from xanthine oxidase. Lastly, we discuss remaining uncertainties inherent both in steady-state oxo 8 dG measurements and in estimates of endogenous oxidation (“hit rates”) based on urinary excretion of oxo 8 dG and oxo 8 Gua.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 1998
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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