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{
"titles": [
"2007 - Trends in oxidative aging theories.pdf",
"2018 - Mechanisms of Vascular Aging.pdf",
"2018 - Nuclear Genomic Instability.pdf",
"2003 - Life-long reduction in MnSOD activity results.pdf",
"2020 - Growth differentiation factor 15 protects against the aging\u2010mediated systemic inflammatory response in humans and mice.pdf",
"2002 - Human mitochondrial DNA with large deletions.pdf",
"2011 - Mitochondrial complex I.pdf",
"2000 - Genome-wide study of aging and oxidative stress.pdf",
"2020 - Clinical Genetics and Genomics of Aging.pdf",
"2012 - Oxidative Stress, Mitochondrial Dysfunction, and Aging.pdf"
],
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"under normal physiological conditions because of an imbal-ance between prooxidants and antioxidants. The imbalanceleads to a steady-state accumulation of oxidative damage in avariety of macromolecules t hat increases during aging, resulting in a progressive loss in the functional efficiency ofvarious cellular processes. In a recent review, Beckman andAmes made a useful addition to this debate by dividing the",
"tributing to impaired bioenergetics in aged cells include oxida-tion/nitration of mitochondrial proteins, destabilization of the macromolecular organization of electron transport chain com-plexes, and impaired mitophagy (a mitochondria-specific form of autophagy). The combination of increased mitochondrial Figure 2. Proposed scheme for mechanisms and pathological consequences of age-related oxidative stress in vascular endothelial cells. The",
"over the years to become the oxidative stress theory of aging, but the principle is the same, inthat the accumulation of oxidative damage drives aging. In support of this theory, a large body of literature indicates that oxidative damage to all cellular macromolecules increases with age. Furthermore, overexpression of antioxidant enzymes that detoxify ROS, such as copper- andzinc-containing superoxide dismutase (SOD), manganese-containing SOD, or catalase, increase",
"predicted from the oxidative stress theory of aging. Thistheory,whichisbasedonthetenetthatdamagecausedbyROSplays a critical role in determining life span, has been one ofthe most popular theories to explain the deterioration in bio-chemical and physiological processes that occur during theaging process. A large number of studies have producedcorrelative data in support of this theory, e.g., an increase inoxidativedamagetolipid,protein,andDNAwithagehasbeendemonstrated in a variety of tissues and organisms",
"during\tthe\taging\tprocess\t(Yi,\tChang,\t&\tShong,\t2018).\tOxidative\tdam - age to cellular macromolecules, or stress arising from mitochondrial DNA\t(mtDNA)\tmutation\tand\tincreased\treactive\toxygen\tspecies\t (ROS),\tis\ta\tkey\thallmark\tof\taging\tphysiology\t(Yi\tet\tal.,\t2018).\tAlthough",
"radical theory of aging, which argues that oxidative damageplays a key role in senescence. Among the numerousmechanisms known to generate oxidants, leakage of super-oxide anion and hydrogen peroxide from the mitochondrialelectron transport chain are the chief candidates. Increased damage to mtDNA could exacerbate this leakage of reactive oxygen species (ROS) (4). It is not known how mtDNA deletions accumulate during",
"most plausible explanation for aging. But, as we have discussed, not all types of damage contribute equally to aging. From this point of view, it seems that ROS generated by complex I (at sulfur iron clusters or flavin sites) may damage specific targets that can alter homeosta - sis in a significant enough way to influ - ence aging. The most obvious target for this damage is mtDNA. The generation of ROS specifically by complex I corre - lates with levels of oxidative damage in mtDNA.",
"increase lifespan also confer resistance to oxidative stress (1).This finding supports the free-radical hypothesis of aging, whichsuggests that reactive oxygen species that accumulate withincreasing age cause oxidative damage to macromolecules (in-cluding nucleic acids, proteins, and lipids) and are causally linkedto aging and death (8, 9). Free radicals have been found toregulate the expression of a number of genes that includeantioxidant defense genes involved in repairing oxidative dam-age, as well as",
"Molecular Biomarkers forOxidative Stress There are many theories that try to explain the nature of aging; however, none of them can explain every aspect of the biology of aging. One of the most accepted and studied is the one proposed by Denham Harman in 1956. This theory proposed that during lifespan organisms accumulate oxidative damage in their biomolecules. Oxidative damage is generated by reactive oxygen species (ROS), which are the",
"production by mitochondria and increased 8-oxo-dG con-tent in the mtDNA are frequently detected in aged tissues [40,4750], suggesting that progressive accumulation of oxidative DNA damage is a contributory factor to the agingprocess. Consistently, many studies have found that increasedoxidative damage in cells is associated with aging [ 5153]. Furthermore, genetic studies in worm, y, and mouse havelinked enhanced stress resistance or reduced free radical"
],
"answer": "Oxidative stress contributes to cellular aging through the accumulation of oxidative damage in various macromolecules, which leads to a decline in cellular function. This process occurs due to an imbalance between prooxidants and antioxidants, resulting in a steady-state accumulation of oxidative damage that increases with age [1]. The oxidative stress theory of aging posits that damage caused by reactive oxygen species (ROS) plays a critical role in determining lifespan, as it leads to the deterioration of biochemical and physiological processes [4]. Oxidative damage affects all cellular macromolecules, including lipids, proteins, and DNA, and this damage increases with age [3]. The accumulation of such damage is a key hallmark of aging physiology [5]. Specifically, oxidative damage to mitochondrial DNA (mtDNA) and the generation of ROS from the mitochondrial electron transport chain are significant contributors to this process [6]. Overall, the accumulation of oxidative damage is causally linked to aging and death, as it impairs cellular processes and bioenergetics, leading to the progressive loss of functional efficiency in cells [2], [8].",
"question": "How do oxidative stress and the subsequent accumulation of damaged macromolecules contribute to cellular aging?"
}
|
