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Abstract


The FreeRadical/Oxidative Stress TheoryofAging,which was first propose din1956,iscurrentl yone of the most popul are xplanations for how aging occurs at the biochemical/molecular level. However, most of the evidence in support of this theory is correlative, e.g., oxidativedamagetovariousbiomoleculesincreaseswithage,andcaloricrestriction,whichincreaseslifespanandretardsaging,reducestheage relatedincreaseinoxidativedamagetobiomolecules.https://www.51lunwen.org/Medical/ ThemostdirecttestoftheFreeRadical/OxidativeStressTheoryofAgingistospecificallyalterthe age-related increase in oxidative damage and determine how this alteration affects life span. For the first time, investigators can usegenetically altered animals to test directly the role of oxidative damage in aging. In this manuscript, we critically review the past research inthis area and discuss potential future research directions in testing the Free Radical/Oxidative Theory of Aging.# 2004 Elsevier Ireland Ltd. All rights reserved.


1. Introduction


The roots of the Free Radical or Oxidative Stress Theoryof Aging date back to the late nineteenth century, whenFenton (1894) discovered that Fe(II) catalyzed the oxidationof tartaric acid by hydrogen peroxide. Haber and Willsta¨tter(1931) and Haber and Weiss (1932) proposed that hydroxylradicals, hydrogen peroxide, and superoxide anions undergoa chain reaction that results in a net conversion of hydrogenperoxideintowater.Thisbecame knownastheHaber–Weissreaction and is now believed to be at the heart of cascadesthat generate most reactiveoxygen species (ROS) in the cell.At this time, oxygen toxicity was known (Binger et al.,1927); however, its connection to free radicals was not yetunderstood.


By the 1950s, in vitro studies suggested that ROS wereproduced within the cell. Using electron spin resonance(ESR), Commoner et al. (1954) published the first directevidence that free radicals were produced in living cells.Theyalsofoundthatfreeradical levelswerehigherintissuesthat were more metabolically active. Subsequently, Harman(1956) published in 1956 the Free Radical Theory of Aging.He integrated evidence from the ESR study, post-Hiroshimastudies of radiation damage (Hempelmann and Hoffman,1953), Fenton’s findings (Fenton, 1894), and contemporarytheories that proposed free mechanisms for the oxidation oforganic compounds and dismutation of hydrogen peroxideby iron salts (Uri, 1952). Harman proposed that physiolo gical iron and other metals would cause ROS to form in thecell via Haber–Weiss chemistry as a by-product of normalredox reactions. The ROS would damage nearby structuresincluding DNA, which would in turn cause mutations. Hepredicted that administering compounds that are easily oxidized, such as cysteine, would slow down the agingprocess.
Over the past two decades, it has become apparent thatmany ROS, such as peroxides, which are not free radicals,also play a role in oxidative damage to cells. Therefore, theFree Radical Theory of Aging was modified to the OxidativeStress Theory of Aging. We will refer to this theorythroughout this review as the Free Radical/Oxidative StressTheory of Aging.


2. Predictions of the free radical/oxidativestress theory of aging
3. Prediction 1: do levels of oxidatively damagedbiomolecules increase with age?
3.1. Lipid peroxidation
3.2. Protein oxidation
3.3. DNA oxidation4. P本论文由英语论文网提供整理，提供论文代写，英语论文代写，代写论文，代写英语论文，代写留学生论文，代写英文论文，留学生论文代写相关核心关键词搜索。