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srcset="//upload.wikimedia.org/wikipedia/en/thumb/b/b4/Ambox_important.svg/60px-Ambox_important.svg.png 1.5x, //upload.wikimedia.org/wikipedia/en/thumb/b/b4/Ambox_important.svg/80px-Ambox_important.svg.png 2x" data-file-width="40" data-file-height="40" /></span></span></div></td><td class="mbox-text"><div class="mbox-text-span">This article <b>needs more <a href="/wiki/Wikipedia:Identifying_reliable_sources_(medicine)" title="Wikipedia:Identifying reliable sources (medicine)">reliable medical references</a> for <a href="/wiki/Wikipedia:Verifiability" title="Wikipedia:Verifiability">verification</a> or relies too heavily on <a href="/wiki/Wikipedia:Primary_sources" class="mw-redirect" title="Wikipedia:Primary sources">primary sources</a></b>.<span class="hide-when-compact"> Please review the contents of the article and <a class="external text" href="https://en.wikipedia.org/w/index.php?title=Free-radical_theory_of_aging&action=edit">add the appropriate references</a> if you can. Unsourced or poorly sourced material may be challenged and <a href="/wiki/Wikipedia:Verifiability#Burden_of_evidence" title="Wikipedia:Verifiability">removed</a>. <small><span class="plainlinks"><i>Find sources:</i> <a rel="nofollow" class="external text" href="https://www.google.com/search?as_eq=wikipedia&q=%22Free-radical+theory+of+aging%22">"Free-radical theory of aging"</a> – <a rel="nofollow" class="external text" href="https://www.google.com/search?tbm=nws&q=%22Free-radical+theory+of+aging%22+-wikipedia&tbs=ar:1">news</a> <b>·</b> <a rel="nofollow" class="external text" href="https://www.google.com/search?&q=%22Free-radical+theory+of+aging%22&tbs=bkt:s&tbm=bks">newspapers</a> <b>·</b> <a rel="nofollow" class="external text" href="https://www.google.com/search?tbs=bks:1&q=%22Free-radical+theory+of+aging%22+-wikipedia">books</a> <b>·</b> <a rel="nofollow" class="external text" href="https://scholar.google.com/scholar?q=%22Free-radical+theory+of+aging%22">scholar</a> <b>·</b> <a rel="nofollow" class="external text" href="https://www.jstor.org/action/doBasicSearch?Query=%22Free-radical+theory+of+aging%22&acc=on&wc=on">JSTOR</a></span></small></span> <span class="date-container"><i>(<span class="date">May 2015</span>)</i></span></div></td><td class="mbox-imageright"><div class="mbox-image-div"><span typeof="mw:File"><span><img src="//upload.wikimedia.org/wikipedia/commons/thumb/a/ae/Star_of_life.svg/52px-Star_of_life.svg.png" decoding="async" width="52" height="50" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/ae/Star_of_life.svg/77px-Star_of_life.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/ae/Star_of_life.svg/103px-Star_of_life.svg.png 2x" data-file-width="198" data-file-height="192" /></span></span></div></td></tr></tbody></table> <p>The <b>free radical theory of aging</b> states that organisms <a href="/wiki/Aging" class="mw-redirect" title="Aging">age</a> because cells accumulate <a href="/wiki/Free_radical" class="mw-redirect" title="Free radical">free radical</a> damage over time.<sup id="cite_ref-1" class="reference"><a href="#cite_note-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> A free radical is any atom or molecule that has a single unpaired electron in an outer shell.<sup id="cite_ref-ReferenceA_2-0" class="reference"><a href="#cite_note-ReferenceA-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> While a few free radicals such as <a href="/wiki/Melanin" title="Melanin">melanin</a> are not <a href="/wiki/Reactivity_(chemistry)" title="Reactivity (chemistry)">chemically reactive</a>, most biologically relevant free radicals are highly reactive.<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> For most biological structures, free radical damage is closely associated with <a href="/wiki/Oxidative_stress" title="Oxidative stress">oxidative</a> damage. <a href="/wiki/Antioxidant" title="Antioxidant">Antioxidants</a> are <a href="/wiki/Reducing_agent" title="Reducing agent">reducing agents</a>, and limit oxidative damage to biological structures by <a href="/wiki/Passivation_(chemistry)" title="Passivation (chemistry)">passivating</a> them from free radicals.<sup id="cite_ref-ReferenceB_4-0" class="reference"><a href="#cite_note-ReferenceB-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> </p><p>Strictly speaking, the free radical theory is only concerned with free radicals such as superoxide ( O<sub>2</sub><sup>−</sup> ), but it has since been expanded to encompass oxidative damage from other <a href="/wiki/Reactive_oxygen_species" title="Reactive oxygen species">reactive oxygen species</a> (ROS) such as <a href="/wiki/Hydrogen_peroxide" title="Hydrogen peroxide">hydrogen peroxide</a> (H<sub>2</sub>O<sub>2</sub>), or <a href="/wiki/Peroxynitrite" title="Peroxynitrite">peroxynitrite</a> (OONO<sup>−</sup>).<sup id="cite_ref-ReferenceB_4-1" class="reference"><a href="#cite_note-ReferenceB-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Denham_Harman" title="Denham Harman">Denham Harman</a> first proposed the free radical theory of aging in the 1950s,<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> and in the 1970s extended the idea to implicate <a href="/wiki/Mitochondria" class="mw-redirect" title="Mitochondria">mitochondrial</a> production of ROS.<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>In some model organisms, such as <a href="/wiki/Yeast" title="Yeast">yeast</a> and <i><a href="/wiki/Drosophila" title="Drosophila">Drosophila</a></i>, there is evidence that reducing oxidative damage can extend lifespan.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> However, in mice, only 1 of the 18 genetic alterations (SOD-1 deletion) that block antioxidant defences, shortened lifespan.<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> Similarly, in <a href="/wiki/Roundworms" class="mw-redirect" title="Roundworms">roundworms</a> (<i><a href="/wiki/Caenorhabditis_elegans" title="Caenorhabditis elegans">Caenorhabditis elegans</a></i>), blocking the production of the naturally occurring antioxidant <a href="/wiki/Superoxide_dismutase" title="Superoxide dismutase">superoxide dismutase</a> has been shown to <i>increase</i> lifespan.<sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> Whether reducing oxidative damage below normal levels is sufficient to extend lifespan remains an open and controversial question. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Background">Background</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=1" title="Edit section: Background"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The free radical theory of aging was conceived by <a href="/wiki/Denham_Harman" title="Denham Harman">Denham Harman</a> in the 1950s, when prevailing scientific opinion held that free radicals were too unstable to exist in biological systems.<sup id="cite_ref-ReferenceC_10-0" class="reference"><a href="#cite_note-ReferenceC-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> This was also before anyone invoked free radicals as a cause of degenerative diseases.<sup id="cite_ref-Harman_D_2009_11-0" class="reference"><a href="#cite_note-Harman_D_2009-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> Two sources inspired Harman: 1) the <a href="/wiki/Rate_of_living_theory" class="mw-redirect" title="Rate of living theory">rate of living theory</a>, which holds that lifespan is an inverse function of metabolic rate which in turn is proportional to oxygen consumption, and 2) <a href="/wiki/Rebeca_Gerschman" title="Rebeca Gerschman">Rebeca Gerschman</a>'s observation that hyperbaric oxygen toxicity and <a href="/wiki/Radiation_toxicity" class="mw-redirect" title="Radiation toxicity">radiation toxicity</a> could be explained by the same underlying phenomenon: oxygen free radicals.<sup id="cite_ref-ReferenceC_10-1" class="reference"><a href="#cite_note-ReferenceC-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Speakman_JR,_Selman_C_2011_255–9_12-0" class="reference"><a href="#cite_note-Speakman_JR,_Selman_C_2011_255–9-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Noting that radiation causes "mutation, cancer and aging", Harman argued that oxygen free radicals produced during normal respiration would cause cumulative damage which would eventually lead to organismal loss of functionality, and ultimately death.<sup id="cite_ref-ReferenceC_10-2" class="reference"><a href="#cite_note-ReferenceC-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Speakman_JR,_Selman_C_2011_255–9_12-1" class="reference"><a href="#cite_note-Speakman_JR,_Selman_C_2011_255–9-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p><p>In later years, the free radical theory was expanded to include not only aging <i>per se</i>, but also age-related diseases.<sup id="cite_ref-Harman_D_2009_11-1" class="reference"><a href="#cite_note-Harman_D_2009-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> Free radical damage within cells has been linked to a range of disorders including <a href="/wiki/Cancer" title="Cancer">cancer</a>, <a href="/wiki/Arthritis" title="Arthritis">arthritis</a>, <a href="/wiki/Atherosclerosis" title="Atherosclerosis">atherosclerosis</a>, <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a>, and <a href="/wiki/Diabetes" title="Diabetes">diabetes</a>.<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> There has been some evidence to suggest that free radicals and some reactive nitrogen species trigger and increase cell death mechanisms within the body such as <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a> and in extreme cases <a href="/wiki/Necrosis" title="Necrosis">necrosis</a>.<sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>In 1972, Harman modified his original theory.<sup id="cite_ref-Harman_D_2009_11-2" class="reference"><a href="#cite_note-Harman_D_2009-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> In its current form, this theory proposes that <a href="/wiki/Reactive_oxygen_species" title="Reactive oxygen species">reactive oxygen species</a> (ROS) that are produced in the <a href="/wiki/Mitochondria" class="mw-redirect" title="Mitochondria">mitochondria</a>, causes damage to certain <a href="/wiki/Macromolecules" class="mw-redirect" title="Macromolecules">macromolecules</a> including <a href="/wiki/Lipids" class="mw-redirect" title="Lipids">lipids</a>, <a href="/wiki/Proteins" class="mw-redirect" title="Proteins">proteins</a> and most importantly mitochondrial DNA.<sup id="cite_ref-Jang_YC,_Remmen_HV_2009_256–60_15-0" class="reference"><a href="#cite_note-Jang_YC,_Remmen_HV_2009_256–60-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> This damage then causes mutations which lead to an increase of ROS production and greatly enhance the accumulation of free radicals within cells.<sup id="cite_ref-Jang_YC,_Remmen_HV_2009_256–60_15-1" class="reference"><a href="#cite_note-Jang_YC,_Remmen_HV_2009_256–60-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> This mitochondrial theory has been more widely accepted that it could play a major role in contributing to the aging process.<sup id="cite_ref-Gruber_J,_Schaffer_S,_Halliwell_B_2008_6554–79_16-0" class="reference"><a href="#cite_note-Gruber_J,_Schaffer_S,_Halliwell_B_2008_6554–79-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p><p>Since Harman first proposed the free radical theory of aging, there have been continual modifications and extensions to his original theory.<sup id="cite_ref-Gruber_J,_Schaffer_S,_Halliwell_B_2008_6554–79_16-1" class="reference"><a href="#cite_note-Gruber_J,_Schaffer_S,_Halliwell_B_2008_6554–79-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Processes">Processes</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=2" title="Edit section: Processes"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-halign-left" typeof="mw:File/Thumb"><a href="/wiki/File:Free-radicals-oxygen.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/3/3f/Free-radicals-oxygen.jpg/321px-Free-radicals-oxygen.jpg" decoding="async" width="321" height="256" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/3f/Free-radicals-oxygen.jpg/482px-Free-radicals-oxygen.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/3/3f/Free-radicals-oxygen.jpg 2x" data-file-width="605" data-file-height="482" /></a><figcaption>In chemistry, a <a href="/wiki/Free_radical" class="mw-redirect" title="Free radical">free radical</a> is any atom, molecule or ion with an unpaired valence electron.</figcaption></figure> <p>Free radicals are atoms or molecules containing unpaired electrons.<sup id="cite_ref-ReferenceA_2-1" class="reference"><a href="#cite_note-ReferenceA-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Electron" title="Electron">Electrons</a> normally exist in pairs in specific <a href="/wiki/Atomic_orbital" title="Atomic orbital">orbitals</a> in atoms or molecules.<sup id="cite_ref-Orchin_M_2005_17-0" class="reference"><a href="#cite_note-Orchin_M_2005-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> Free radicals, which contain only a single electron in any orbital, are usually unstable toward losing or picking up an extra electron, so that all electrons in the atom or molecule will be paired.<sup id="cite_ref-Orchin_M_2005_17-1" class="reference"><a href="#cite_note-Orchin_M_2005-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p><p>The unpaired electron does not imply charge; free radicals can be positively charged, negatively charged, or neutral. </p><p>Damage occurs when the free radical encounters another molecule and seeks to find another electron to pair its unpaired electron. The free radical often pulls an electron off a neighboring molecule, causing the affected molecule to become a free radical itself. The new free radical can then pull an electron off the next molecule, and a chemical <a href="/wiki/Chain_reaction" title="Chain reaction">chain reaction</a> of radical production occurs.<sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> The free radicals produced in such reactions often terminate by removing an electron from a molecule which becomes changed or cannot function without it, especially in biology. Such an event causes damage to the molecule, and thus to the cell that contains it (since the molecule often becomes dysfunctional). </p><p>The chain reaction caused by free radicals can lead to cross-linking of atomic structures. In cases where the free radical-induced chain reaction involves <a href="/wiki/Base_pair" title="Base pair">base pair</a> molecules in a strand of DNA, the DNA can become cross-linked.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p><p>Oxidative free radicals, such as the <a href="/wiki/Hydroxyl_radical" title="Hydroxyl radical">hydroxyl radical</a> and the <a href="/wiki/Superoxide" title="Superoxide">superoxide</a> radical, can cause <a href="/wiki/DNA_damage_(naturally_occurring)" title="DNA damage (naturally occurring)">DNA damages</a>, and such damages have been proposed to play a key role in the aging of crucial tissues.<sup id="cite_ref-Gensler1987_20-0" class="reference"><a href="#cite_note-Gensler1987-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> DNA damage can result in reduced <a href="/wiki/Gene_expression" title="Gene expression">gene expression</a>, cell death and ultimately tissue dysfunction.<sup id="cite_ref-Gensler1987_20-1" class="reference"><a href="#cite_note-Gensler1987-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Crosslinking_of_DNA" title="Crosslinking of DNA">DNA cross-linking</a> can in turn lead to various effects of aging, especially <a href="/wiki/Cancer" title="Cancer">cancer</a>.<sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> Other cross-linking can occur between <a href="/wiki/Fat" title="Fat">fat</a> and <a href="/wiki/Protein" title="Protein">protein</a> molecules, which leads to wrinkles.<sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> Free radicals can oxidize <a href="/wiki/LDL" class="mw-redirect" title="LDL">LDL</a>, and this is a key event in the formation of plaque in arteries, leading to <a href="/wiki/Heart_disease" class="mw-redirect" title="Heart disease">heart disease</a> and <a href="/wiki/Stroke" title="Stroke">stroke</a>.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> These are examples of how the free-radical theory of aging has been used to neatly "explain" the origin of many <a href="/wiki/Chronic_disease" class="mw-redirect" title="Chronic disease">chronic diseases</a>.<sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p><p>Free radicals that are thought to be involved in the process of aging include <a href="/wiki/Superoxide" title="Superoxide">superoxide</a> and <a href="/wiki/Nitric_oxide" title="Nitric oxide">nitric oxide</a>.<sup id="cite_ref-Afanas'ev_IB_2005_283–90_25-0" class="reference"><a href="#cite_note-Afanas'ev_IB_2005_283–90-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> Specifically, an increase in superoxide affects aging whereas a decrease in nitric oxide formation, or its bioavailability, does the same.<sup id="cite_ref-Afanas'ev_IB_2005_283–90_25-1" class="reference"><a href="#cite_note-Afanas'ev_IB_2005_283–90-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Antioxidant" title="Antioxidant">Antioxidants</a> are helpful in reducing and preventing damage from free radical reactions because of their ability to donate electrons which neutralize the radical without forming another. <a href="/wiki/Vitamin_C" title="Vitamin C">Vitamin C</a>, for example, can lose an electron to a free radical and remain stable itself by passing its unstable electron around the antioxidant molecule.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (August 2023)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading2"><h2 id="Modifications_of_the_theory">Modifications of the theory</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=3" title="Edit section: Modifications of the theory"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>One of the main criticisms of the free radical theory of aging is directed at the suggestion that free radicals are responsible for the damage of <a href="/wiki/Biomolecule" title="Biomolecule">biomolecules</a>, thus being a major reason for <a href="/wiki/Cellular_senescence" title="Cellular senescence">cellular senescence</a> and organismal aging.<sup id="cite_ref-Afanas'ev_I_2010_75–88_26-0" class="reference"><a href="#cite_note-Afanas'ev_I_2010_75–88-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup class="reference nowrap"><span title="Page / location: 81">: 81 </span></sup> Several modifications have been proposed to integrate current research into the overall theory. </p> <div class="mw-heading mw-heading3"><h3 id="Mitochondria">Mitochondria</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=4" title="Edit section: Mitochondria"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Mitochondrial_theory_of_ageing" title="Mitochondrial theory of ageing">Mitochondrial theory of ageing</a></div> <figure typeof="mw:File/Thumb"><a href="/wiki/File:Major_cellular_sources_of_Reactive_Oxygen_Species_in_living_cells.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/f/f8/Major_cellular_sources_of_Reactive_Oxygen_Species_in_living_cells.jpg/370px-Major_cellular_sources_of_Reactive_Oxygen_Species_in_living_cells.jpg" decoding="async" width="370" height="493" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/f/f8/Major_cellular_sources_of_Reactive_Oxygen_Species_in_living_cells.jpg/555px-Major_cellular_sources_of_Reactive_Oxygen_Species_in_living_cells.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/f/f8/Major_cellular_sources_of_Reactive_Oxygen_Species_in_living_cells.jpg/740px-Major_cellular_sources_of_Reactive_Oxygen_Species_in_living_cells.jpg 2x" data-file-width="1200" data-file-height="1600" /></a><figcaption>Major sources of <a href="/wiki/Reactive_oxygen_species" title="Reactive oxygen species">reactive oxygen species</a> in living systems</figcaption></figure> <p>The mitochondrial theory of aging was first proposed in 1978,<sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> and two years later, the mitochondrial free-radical theory of aging was introduced.<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> The theory implicates the mitochondria as the chief target of radical damage, since there is a known chemical mechanism by which mitochondria can produce ROS, mitochondrial components such as <a href="/wiki/MtDNA" class="mw-redirect" title="MtDNA">mtDNA</a> are not as well protected as nuclear DNA, and by studies comparing damage to nuclear and mtDNA that demonstrate higher levels of radical damage on the mitochondrial molecules.<sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> Electrons may escape from <a href="/wiki/Cellular_respiration" title="Cellular respiration">metabolic</a> processes in the mitochondria like the <a href="/wiki/Electron_transport_chain" title="Electron transport chain">Electron transport chain</a>, and these electrons may in turn react with water to form ROS such as the <a href="/wiki/Superoxide_radical" class="mw-redirect" title="Superoxide radical">superoxide radical</a>, or via an indirect route the <a href="/wiki/Hydroxyl_radical" title="Hydroxyl radical">hydroxyl radical</a>. These radicals then damage the mitochondria's DNA and proteins, and these damage components in turn are more liable to produce ROS byproducts. Thus a <a href="/wiki/Positive_feedback_loop" class="mw-redirect" title="Positive feedback loop">positive feedback loop</a> of oxidative stress is established that, over time, can lead to the deterioration of cells and later organs and the entire body.<sup id="cite_ref-Afanas'ev_I_2010_75–88_26-1" class="reference"><a href="#cite_note-Afanas'ev_I_2010_75–88-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> </p><p>This theory has been widely debated<sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> and it is still unclear how ROS induced mtDNA mutations develop.<sup id="cite_ref-Afanas'ev_I_2010_75–88_26-2" class="reference"><a href="#cite_note-Afanas'ev_I_2010_75–88-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> Conte et al. suggest iron-substituted zinc fingers may generate free radicals due to the zinc finger proximity to DNA and thus lead to DNA damage.<sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> </p><p>Afanas'ev suggests the superoxide dismutation activity of CuZnSOD demonstrates an important link between life span and free radicals.<sup id="cite_ref-autogenerated1_33-0" class="reference"><a href="#cite_note-autogenerated1-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> The link between CuZnSOD and life span was demonstrated by Perez et al. who indicated mice life span was affected by the deletion of the Sod1 gene which encodes CuZnSOD.<sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> </p><p>Contrary to the usually observed association between mitochondrial ROS (mtROS) and a decline in longevity, Yee et al. recently observed increased longevity mediated by mtROS signaling in an apoptosis pathway. This serves to support the possibility that observed correlations between ROS damage and aging are not necessarily indicative of the causal involvement of ROS in the aging process but are more likely due to their modulating signal transduction pathways that are part of cellular responses to the aging process.<sup id="cite_ref-35" class="reference"><a href="#cite_note-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Epigenetic_oxidative_redox_shift">Epigenetic oxidative redox shift</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=5" title="Edit section: Epigenetic oxidative redox shift"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Brewer proposed a theory which integrates the free radical theory of aging with the <a href="/wiki/Insulin" title="Insulin">insulin</a> signalling effects in aging.<sup id="cite_ref-Brewer_GJ_2010_173–9_36-0" class="reference"><a href="#cite_note-Brewer_GJ_2010_173–9-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> Brewer's theory suggests "sedentary behaviour associated with age triggers an oxidized <a href="/wiki/Redox" title="Redox">redox</a> shift and impaired mitochondrial function".<sup id="cite_ref-Brewer_GJ_2010_173–9_36-1" class="reference"><a href="#cite_note-Brewer_GJ_2010_173–9-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> This mitochondrial impairment leads to more sedentary behaviour and accelerated aging.<sup id="cite_ref-Brewer_GJ_2010_173–9_36-2" class="reference"><a href="#cite_note-Brewer_GJ_2010_173–9-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Metabolic_stability">Metabolic stability</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=6" title="Edit section: Metabolic stability"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The metabolic stability theory of aging suggests it is the cells ability to maintain stable concentration of ROS which is the primary determinant of lifespan.<sup id="cite_ref-Brink_TC,_Demetrius_L,_Lehrach_H,_Adjaye_J_2009_549–64_37-0" class="reference"><a href="#cite_note-Brink_TC,_Demetrius_L,_Lehrach_H,_Adjaye_J_2009_549–64-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> This theory criticizes the free radical theory because it ignores that ROS are specific signalling molecules which are necessary for maintaining normal cell functions.<sup id="cite_ref-Brink_TC,_Demetrius_L,_Lehrach_H,_Adjaye_J_2009_549–64_37-1" class="reference"><a href="#cite_note-Brink_TC,_Demetrius_L,_Lehrach_H,_Adjaye_J_2009_549–64-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Mitohormesis">Mitohormesis</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=7" title="Edit section: Mitohormesis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Oxidative stress may promote life expectancy of <i><a href="/wiki/Caenorhabditis_elegans" title="Caenorhabditis elegans">Caenorhabditis elegans</a></i> by inducing a secondary response to initially increased levels of ROS.<sup id="cite_ref-Glucose_Restriction_38-0" class="reference"><a href="#cite_note-Glucose_Restriction-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> In mammals, the question of the net effect of reactive oxygen species on aging is even less clear.<sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> Recent <a href="/wiki/Epidemiological" class="mw-redirect" title="Epidemiological">epidemiological</a> findings support the process of mitohormesis in humans, and even suggest that the intake of exogenous antioxidants may increase disease <a href="/wiki/Prevalence" title="Prevalence">prevalence</a> in humans (according to the theory, because they prevent the stimulation of the organism's natural response to the oxidant compounds which not only neutralizes them but provides other benefits as well).<sup id="cite_ref-42" class="reference"><a href="#cite_note-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Challenges">Challenges</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=8" title="Edit section: Challenges"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Birds">Birds</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=9" title="Edit section: Birds"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Among birds, <a href="/wiki/Parrot" title="Parrot">parrots</a> live about five times longer than <a href="/wiki/Quail" title="Quail">quail</a>. ROS production in heart, skeletal muscle, liver and intact erythrocytes was found to be similar in parrots and quail and showed no correspondence with longevity difference.<sup id="cite_ref-Montgomery_43-0" class="reference"><a href="#cite_note-Montgomery-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> These findings were concluded to cast doubt on the robustness of the oxidative stress theory of aging.<sup id="cite_ref-Montgomery_43-1" class="reference"><a href="#cite_note-Montgomery-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=10" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Life_extension" title="Life extension">Life extension</a></li> <li><a href="/wiki/List_of_life_extension-related_topics" class="mw-redirect" title="List of life extension-related topics">List of life extension-related topics</a></li> <li><a href="/wiki/Senescence" title="Senescence">Senescence</a></li> <li><a href="/wiki/Mitochondrial_theory_of_ageing" title="Mitochondrial theory of ageing">Mitochondrial theory of ageing</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Free-radical_theory_of_aging&action=edit&section=11" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist"> <div class="mw-references-wrap mw-references-columns"><ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text">Hekimi S, Lapointe J, Wen Y. Taking a "good" look at free radicals in the aging process. Trends In Cell Biology. 2011;21(10) 569-76.</span> </li> <li id="cite_note-ReferenceA-2"><span class="mw-cite-backlink">^ <a href="#cite_ref-ReferenceA_2-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-ReferenceA_2-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text">Erbas M, Sekerci H. "Importance of Free Radicals and Occurring During Food Processing". Serbest Radïkallerïn Onemï Ve Gida Ïsleme Sirasinda Olusumu. 2011: 36(6) 349–56.</span> </li> <li id="cite_note-3"><span class="mw-cite-backlink"><b><a href="#cite_ref-3">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFHerrlingJungFuchs2008" class="citation journal cs1">Herrling T, Jung K, Fuchs J (2008). "The role of melanin as protector against free radicals in skin and its role as free radical indicator in hair". <i>Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy</i>. <b>69</b> (5): 1429–35. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2008AcSpA..69.1429H">2008AcSpA..69.1429H</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.saa.2007.09.030">10.1016/j.saa.2007.09.030</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17988942">17988942</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Spectrochimica+Acta+Part+A%3A+Molecular+and+Biomolecular+Spectroscopy&rft.atitle=The+role+of+melanin+as+protector+against+free+radicals+in+skin+and+its+role+as+free+radical+indicator+in+hair&rft.volume=69&rft.issue=5&rft.pages=1429-35&rft.date=2008&rft_id=info%3Apmid%2F17988942&rft_id=info%3Adoi%2F10.1016%2Fj.saa.2007.09.030&rft_id=info%3Abibcode%2F2008AcSpA..69.1429H&rft.aulast=Herrling&rft.aufirst=T&rft.au=Jung%2C+K&rft.au=Fuchs%2C+J&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-ReferenceB-4"><span class="mw-cite-backlink">^ <a href="#cite_ref-ReferenceB_4-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-ReferenceB_4-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHalliwell_B2012" class="citation journal cs1">Halliwell B (2012). <a rel="nofollow" class="external text" href="https://doi.org/10.1111%2Fj.1753-4887.2012.00476.x">"Free radicals and antioxidants: updating a personal view"</a>. <i>Nutrition Reviews</i>. <b>70</b> (5): 257–65. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1111%2Fj.1753-4887.2012.00476.x">10.1111/j.1753-4887.2012.00476.x</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22537212">22537212</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nutrition+Reviews&rft.atitle=Free+radicals+and+antioxidants%3A+updating+a+personal+view&rft.volume=70&rft.issue=5&rft.pages=257-65&rft.date=2012&rft_id=info%3Adoi%2F10.1111%2Fj.1753-4887.2012.00476.x&rft_id=info%3Apmid%2F22537212&rft.au=Halliwell+B&rft_id=https%3A%2F%2Fdoi.org%2F10.1111%252Fj.1753-4887.2012.00476.x&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-5"><span class="mw-cite-backlink"><b><a href="#cite_ref-5">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHarman,_D1956" class="citation journal cs1">Harman, D (1956). "Aging: a theory based on free radical and radiation chemistry". <i>Journal of Gerontology</i>. <b>11</b> (3): 298–300. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1093%2Fgeronj%2F11.3.298">10.1093/geronj/11.3.298</a>. <a href="/wiki/Hdl_(identifier)" class="mw-redirect" title="Hdl (identifier)">hdl</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://hdl.handle.net/2027%2Fmdp.39015086547422">2027/mdp.39015086547422</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/13332224">13332224</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Gerontology&rft.atitle=Aging%3A+a+theory+based+on+free+radical+and+radiation+chemistry&rft.volume=11&rft.issue=3&rft.pages=298-300&rft.date=1956&rft_id=info%3Ahdl%2F2027%2Fmdp.39015086547422&rft_id=info%3Apmid%2F13332224&rft_id=info%3Adoi%2F10.1093%2Fgeronj%2F11.3.298&rft.au=Harman%2C+D&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-6"><span class="mw-cite-backlink"><b><a href="#cite_ref-6">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHarman,_D1972" class="citation journal cs1">Harman, D (1972). "A biologic clock: the mitochondria?". <i>Journal of the American Geriatrics Society</i>. <b>20</b> (4): 145–147. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1111%2Fj.1532-5415.1972.tb00787.x">10.1111/j.1532-5415.1972.tb00787.x</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/5016631">5016631</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:396830">396830</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+the+American+Geriatrics+Society&rft.atitle=A+biologic+clock%3A+the+mitochondria%3F&rft.volume=20&rft.issue=4&rft.pages=145-147&rft.date=1972&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A396830%23id-name%3DS2CID&rft_id=info%3Apmid%2F5016631&rft_id=info%3Adoi%2F10.1111%2Fj.1532-5415.1972.tb00787.x&rft.au=Harman%2C+D&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-7"><span class="mw-cite-backlink"><b><a href="#cite_ref-7">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFFontanaPartridgeLongo2010" class="citation journal cs1">Fontana, Luigi; Partridge, Linda; Longo, Valter D. (16 April 2010). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607354">"Extending Healthy Life Span—From Yeast to Humans"</a>. <i>Science</i>. <b>328</b> (5976): 321–326. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2010Sci...328..321F">2010Sci...328..321F</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1126%2Fscience.1172539">10.1126/science.1172539</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607354">3607354</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/20395504">20395504</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Science&rft.atitle=Extending+Healthy+Life+Span%E2%80%94From+Yeast+to+Humans&rft.volume=328&rft.issue=5976&rft.pages=321-326&rft.date=2010-04-16&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3607354%23id-name%3DPMC&rft_id=info%3Apmid%2F20395504&rft_id=info%3Adoi%2F10.1126%2Fscience.1172539&rft_id=info%3Abibcode%2F2010Sci...328..321F&rft.aulast=Fontana&rft.aufirst=Luigi&rft.au=Partridge%2C+Linda&rft.au=Longo%2C+Valter+D.&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3607354&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-8"><span class="mw-cite-backlink"><b><a href="#cite_ref-8">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFPérezBokovRemmenMele2009" class="citation journal cs1">Pérez VI, Bokov A, Remmen HV, Mele J, Ran Q, Ikeno Y, et al. (2009). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789432">"Is the oxidative stress theory of aging dead?"</a>. <i>Biochimica et Biophysica Acta (BBA) - General Subjects</i>. <b>1790</b> (10): 1005–14. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.bbagen.2009.06.003">10.1016/j.bbagen.2009.06.003</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789432">2789432</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19524016">19524016</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Biochimica+et+Biophysica+Acta+%28BBA%29+-+General+Subjects&rft.atitle=Is+the+oxidative+stress+theory+of+aging+dead%3F&rft.volume=1790&rft.issue=10&rft.pages=1005-14&rft.date=2009&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2789432%23id-name%3DPMC&rft_id=info%3Apmid%2F19524016&rft_id=info%3Adoi%2F10.1016%2Fj.bbagen.2009.06.003&rft.aulast=P%C3%A9rez&rft.aufirst=VI&rft.au=Bokov%2C+A&rft.au=Remmen%2C+HV&rft.au=Mele%2C+J&rft.au=Ran%2C+Q&rft.au=Ikeno%2C+Y&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2789432&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-9"><span class="mw-cite-backlink"><b><a href="#cite_ref-9">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFVan_RammsdonkHekimi2009" class="citation journal cs1">Van Rammsdonk, Jeremy M.; Hekimi, Siegfried (2009). Kim, Stuart K. (ed.). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628729">"Deletion of the Mitochondrial Superoxide Dismutase sod-2 Extends Lifespan in <i>Caenorhabditis elegans</i>"</a>. <i>PLOS Genetics</i>. <b>5</b> (2): e1000361. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1371%2Fjournal.pgen.1000361">10.1371/journal.pgen.1000361</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628729">2628729</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19197346">19197346</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=PLOS+Genetics&rft.atitle=Deletion+of+the+Mitochondrial+Superoxide+Dismutase+sod-2+Extends+Lifespan+in+Caenorhabditis+elegans&rft.volume=5&rft.issue=2&rft.pages=e1000361&rft.date=2009&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2628729%23id-name%3DPMC&rft_id=info%3Apmid%2F19197346&rft_id=info%3Adoi%2F10.1371%2Fjournal.pgen.1000361&rft.aulast=Van+Rammsdonk&rft.aufirst=Jeremy+M.&rft.au=Hekimi%2C+Siegfried&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2628729&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-ReferenceC-10"><span class="mw-cite-backlink">^ <a href="#cite_ref-ReferenceC_10-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-ReferenceC_10-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-ReferenceC_10-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHarman_D1956" class="citation journal cs1">Harman D (Jul 1956). "Aging: a theory based on free radical and radiation chemistry". <i>J Gerontol</i>. <b>11</b> (3): 298–300. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1093%2Fgeronj%2F11.3.298">10.1093/geronj/11.3.298</a>. <a href="/wiki/Hdl_(identifier)" class="mw-redirect" title="Hdl (identifier)">hdl</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://hdl.handle.net/2027%2Fmdp.39015086547422">2027/mdp.39015086547422</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/13332224">13332224</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=J+Gerontol&rft.atitle=Aging%3A+a+theory+based+on+free+radical+and+radiation+chemistry&rft.volume=11&rft.issue=3&rft.pages=298-300&rft.date=1956-07&rft_id=info%3Ahdl%2F2027%2Fmdp.39015086547422&rft_id=info%3Apmid%2F13332224&rft_id=info%3Adoi%2F10.1093%2Fgeronj%2F11.3.298&rft.au=Harman+D&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Harman_D_2009-11"><span class="mw-cite-backlink">^ <a href="#cite_ref-Harman_D_2009_11-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Harman_D_2009_11-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Harman_D_2009_11-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFHarman_D2009" class="citation journal cs1">Harman D (2009). "Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009". <i>Biogerontology</i>. <b>10</b> (6): 773–81. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1007%2Fs10522-009-9234-2">10.1007/s10522-009-9234-2</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19466577">19466577</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:13512659">13512659</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Biogerontology&rft.atitle=Origin+and+evolution+of+the+free+radical+theory+of+aging%3A+a+brief+personal+history%2C+1954%E2%80%932009&rft.volume=10&rft.issue=6&rft.pages=773-81&rft.date=2009&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A13512659%23id-name%3DS2CID&rft_id=info%3Apmid%2F19466577&rft_id=info%3Adoi%2F10.1007%2Fs10522-009-9234-2&rft.au=Harman+D&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Speakman_JR,_Selman_C_2011_255–9-12"><span class="mw-cite-backlink">^ <a href="#cite_ref-Speakman_JR,_Selman_C_2011_255–9_12-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Speakman_JR,_Selman_C_2011_255–9_12-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFSpeakmanSelman2011" class="citation journal cs1">Speakman JR, Selman C (2011). "The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan". <i>BioEssays</i>. <b>33</b> (4): 255–9. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1002%2Fbies.201000132">10.1002/bies.201000132</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21290398">21290398</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:13720843">13720843</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=BioEssays&rft.atitle=The+free-radical+damage+theory%3A+Accumulating+evidence+against+a+simple+link+of+oxidative+stress+to+ageing+and+lifespan&rft.volume=33&rft.issue=4&rft.pages=255-9&rft.date=2011&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A13720843%23id-name%3DS2CID&rft_id=info%3Apmid%2F21290398&rft_id=info%3Adoi%2F10.1002%2Fbies.201000132&rft.aulast=Speakman&rft.aufirst=JR&rft.au=Selman%2C+C&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-13"><span class="mw-cite-backlink"><b><a href="#cite_ref-13">^</a></b></span> <span class="reference-text">Clancy D, Birdsall J. Flies, worms and the Free Radical Theory of ageing. Ageing Research Reviews. (0).</span> </li> <li id="cite_note-14"><span class="mw-cite-backlink"><b><a href="#cite_ref-14">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFChatterjeeLardinoisBhattacharjeeTucker2011" class="citation journal cs1">Chatterjee S, Lardinois O, Bhattacharjee S, Tucker J, Corbett J, Deterding L, et al. (2011). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051032">"Oxidative stress induces protein and DNA radical formation in follicular dendritic cells of the germinal center and modulates its cell death patterns in late sepsis"</a>. <i>Free Radical Biology and Medicine</i>. <b>50</b> (8): 988–99. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.freeradbiomed.2010.12.037">10.1016/j.freeradbiomed.2010.12.037</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051032">3051032</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21215311">21215311</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Free+Radical+Biology+and+Medicine&rft.atitle=Oxidative+stress+induces+protein+and+DNA+radical+formation+in+follicular+dendritic+cells+of+the+germinal+center+and+modulates+its+cell+death+patterns+in+late+sepsis&rft.volume=50&rft.issue=8&rft.pages=988-99&rft.date=2011&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3051032%23id-name%3DPMC&rft_id=info%3Apmid%2F21215311&rft_id=info%3Adoi%2F10.1016%2Fj.freeradbiomed.2010.12.037&rft.aulast=Chatterjee&rft.aufirst=S&rft.au=Lardinois%2C+O&rft.au=Bhattacharjee%2C+S&rft.au=Tucker%2C+J&rft.au=Corbett%2C+J&rft.au=Deterding%2C+L&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3051032&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Jang_YC,_Remmen_HV_2009_256–60-15"><span class="mw-cite-backlink">^ <a href="#cite_ref-Jang_YC,_Remmen_HV_2009_256–60_15-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Jang_YC,_Remmen_HV_2009_256–60_15-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFJangRemmen2009" class="citation journal cs1">Jang YC, Remmen HV (2009). "The mitochondrial theory of aging: Insight from transgenic and knockout mouse models". <i>Experimental Gerontology</i>. <b>44</b> (4): 256–60. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.exger.2008.12.006">10.1016/j.exger.2008.12.006</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19171187">19171187</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:19815246">19815246</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Experimental+Gerontology&rft.atitle=The+mitochondrial+theory+of+aging%3A+Insight+from+transgenic+and+knockout+mouse+models&rft.volume=44&rft.issue=4&rft.pages=256-60&rft.date=2009&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A19815246%23id-name%3DS2CID&rft_id=info%3Apmid%2F19171187&rft_id=info%3Adoi%2F10.1016%2Fj.exger.2008.12.006&rft.aulast=Jang&rft.aufirst=YC&rft.au=Remmen%2C+HV&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Gruber_J,_Schaffer_S,_Halliwell_B_2008_6554–79-16"><span class="mw-cite-backlink">^ <a href="#cite_ref-Gruber_J,_Schaffer_S,_Halliwell_B_2008_6554–79_16-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Gruber_J,_Schaffer_S,_Halliwell_B_2008_6554–79_16-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFGruberSchafferHalliwell2008" class="citation journal cs1">Gruber J, Schaffer S, Halliwell B (2008). <a rel="nofollow" class="external text" href="https://doi.org/10.2741%2F3174">"The mitochondrial free radical theory of ageing—where do we stand?"</a>. <i>Frontiers in Bioscience</i>. <b>13</b> (13): 6554–79. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.2741%2F3174">10.2741/3174</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/18508680">18508680</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Frontiers+in+Bioscience&rft.atitle=The+mitochondrial+free+radical+theory+of+ageing%E2%80%94where+do+we+stand%3F&rft.volume=13&rft.issue=13&rft.pages=6554-79&rft.date=2008&rft_id=info%3Adoi%2F10.2741%2F3174&rft_id=info%3Apmid%2F18508680&rft.aulast=Gruber&rft.aufirst=J&rft.au=Schaffer%2C+S&rft.au=Halliwell%2C+B&rft_id=https%3A%2F%2Fdoi.org%2F10.2741%252F3174&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Orchin_M_2005-17"><span class="mw-cite-backlink">^ <a href="#cite_ref-Orchin_M_2005_17-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Orchin_M_2005_17-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text">Orchin M, Macomber RS, Pinhas A, Wilson RM, editors. The Vocabulary and Concepts of Organic Chemistry. 2 ed: John Wiley & Sons; 2005.</span> </li> <li id="cite_note-18"><span class="mw-cite-backlink"><b><a href="#cite_ref-18">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCui_HangKong_YahuiZhang_Hong2011" class="citation journal cs1">Cui Hang; Kong Yahui; Zhang Hong (2011). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184498">"Oxidative Stress, Mitochondrial Dysfunction, and Aging"</a>. <i>Journal of Signal Transduction</i>. <b>2012</b>: 646354. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1155%2F2012%2F646354">10.1155/2012/646354</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184498">3184498</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21977319">21977319</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Signal+Transduction&rft.atitle=Oxidative+Stress%2C+Mitochondrial+Dysfunction%2C+and+Aging&rft.volume=2012&rft.pages=646354&rft.date=2011&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3184498%23id-name%3DPMC&rft_id=info%3Apmid%2F21977319&rft_id=info%3Adoi%2F10.1155%2F2012%2F646354&rft.au=Cui+Hang&rft.au=Kong+Yahui&rft.au=Zhang+Hong&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3184498&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-19"><span class="mw-cite-backlink"><b><a href="#cite_ref-19">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCreanGeacintovShafirovich2008" class="citation journal cs1">Crean C, Geacintov NE, Shafirovich V (2008). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577587">"Intrastrand G-U cross-links generated by the oxidation of guanine in 5′-d(GCU) and 5′-r(GCU)"</a>. <i>Free Radical Biology and Medicine</i>. <b>45</b> (8): 1125–34. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.freeradbiomed.2008.07.008">10.1016/j.freeradbiomed.2008.07.008</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577587">2577587</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/18692567">18692567</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Free+Radical+Biology+and+Medicine&rft.atitle=Intrastrand+G-U+cross-links+generated+by+the+oxidation+of+guanine+in+5%E2%80%B2-d%28GCU%29+and+5%E2%80%B2-r%28GCU%29&rft.volume=45&rft.issue=8&rft.pages=1125-34&rft.date=2008&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2577587%23id-name%3DPMC&rft_id=info%3Apmid%2F18692567&rft_id=info%3Adoi%2F10.1016%2Fj.freeradbiomed.2008.07.008&rft.aulast=Crean&rft.aufirst=C&rft.au=Geacintov%2C+NE&rft.au=Shafirovich%2C+V&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2577587&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Gensler1987-20"><span class="mw-cite-backlink">^ <a href="#cite_ref-Gensler1987_20-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Gensler1987_20-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text">Gensler, H.L., Hall, J.J., and Bernstein, H. (1987). The DNA damage hypothesis of aging: Importance of oxidative damage. In "Review of Biological Research in Aging." Vol. 3 (M. Rothstein, ed.), pp. 451–465. Alan R. Liss, New York</span> </li> <li id="cite_note-21"><span class="mw-cite-backlink"><b><a href="#cite_ref-21">^</a></b></span> <span class="reference-text">Dizdaroglu M, Jaruga P. Mechanisms of free radical-induced damage to DNA. Free Radical Research. [Article]. 2012;46(4) 382–419.</span> </li> <li id="cite_note-22"><span class="mw-cite-backlink"><b><a href="#cite_ref-22">^</a></b></span> <span class="reference-text">Pageon H, Asselineau D. An in Vitro Approach to the Chronological Aging of Skin by Glycation of the Collagen: The Biological Effect of Glycation on the Reconstructed Skin Model" <i>Annals of the New York Academy of Sciences</i> 2005;1043(1) 529-32.</span> </li> <li id="cite_note-23"><span class="mw-cite-backlink"><b><a href="#cite_ref-23">^</a></b></span> <span class="reference-text">Bamm VV, Tsemakhovich VA, Shaklai N. Oxidation of low-density lipoprotein by hemoglobin–hemichrome. The International Journal of Biochemistry & Cell Biology. 2003;35(3) 349-58.</span> </li> <li id="cite_note-24"><span class="mw-cite-backlink"><b><a href="#cite_ref-24">^</a></b></span> <span class="reference-text">C. Richter, JW Park, BN Ames <a rel="nofollow" class="external text" href="http://www.pnas.org/content/85/17/6465.short">"Normal oxidative damage to mitochondrial and nuclear DNA is extensive"</a> "PNAS", 1988.</span> </li> <li id="cite_note-Afanas'ev_IB_2005_283–90-25"><span class="mw-cite-backlink">^ <a href="#cite_ref-Afanas'ev_IB_2005_283–90_25-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Afanas'ev_IB_2005_283–90_25-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAfanas'ev_IB2005" class="citation journal cs1">Afanas'ev IB (2005). "Free radical mechanisms of aging processes under physiological conditions". <i>Biogerontology</i>. <b>6</b> (4): 283–90. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1007%2Fs10522-005-2626-z">10.1007/s10522-005-2626-z</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16333762">16333762</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:7661778">7661778</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Biogerontology&rft.atitle=Free+radical+mechanisms+of+aging+processes+under+physiological+conditions&rft.volume=6&rft.issue=4&rft.pages=283-90&rft.date=2005&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A7661778%23id-name%3DS2CID&rft_id=info%3Apmid%2F16333762&rft_id=info%3Adoi%2F10.1007%2Fs10522-005-2626-z&rft.au=Afanas%27ev+IB&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Afanas'ev_I_2010_75–88-26"><span class="mw-cite-backlink">^ <a href="#cite_ref-Afanas'ev_I_2010_75–88_26-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Afanas'ev_I_2010_75–88_26-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Afanas'ev_I_2010_75–88_26-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAfanas'ev_I2010" class="citation journal cs1">Afanas'ev I (2010). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295029">"Signaling and Damaging Functions of Free Radicals in Aging-Free Radical Theory, Hormesis, and TOR"</a>. <i>Aging and Disease</i>. <b>1</b> (2): 75–88. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295029">3295029</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22396858">22396858</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Aging+and+Disease&rft.atitle=Signaling+and+Damaging+Functions+of+Free+Radicals+in+Aging-Free+Radical+Theory%2C+Hormesis%2C+and+TOR&rft.volume=1&rft.issue=2&rft.pages=75-88&rft.date=2010&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3295029%23id-name%3DPMC&rft_id=info%3Apmid%2F22396858&rft.au=Afanas%27ev+I&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3295029&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-27"><span class="mw-cite-backlink"><b><a href="#cite_ref-27">^</a></b></span> <span class="reference-text">Lobachev A.N.<link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation cs2"><a rel="nofollow" class="external text" href="http://aiexandr2010.narod.ru/rol.pdf"><i>Role of mitochondrial processes in the development and aging of organism. Aging and cancer</i></a> <span class="cs1-format">(PDF)</span>, Chemical abstracts. 1979 v. 91 N 25 91:208561v.Deposited Doc., VINITI 2172-78, 1978, p. 48</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Role+of+mitochondrial+processes+in+the+development+and+aging+of+organism.+Aging+and+cancer&rft.pages=48&rft.pub=Chemical+abstracts.+1979+v.+91+N+25+91%3A208561v.Deposited+Doc.%2C+VINITI+2172-78&rft.date=1978&rft_id=http%3A%2F%2Faiexandr2010.narod.ru%2Frol.pdf&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-28"><span class="mw-cite-backlink"><b><a href="#cite_ref-28">^</a></b></span> <span class="reference-text">Lobachev A.N.<link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation cs2"><a rel="nofollow" class="external text" href="http://aiexandr2010.narod.ru/Biogenesis.pdf"><i>Biogenesis of mitochondria during cell differentiation and aging</i></a> <span class="cs1-format">(PDF)</span>, Deposited Doc. VINITI 19.09.85, №6756-В85, 1985, p. 28</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Biogenesis+of+mitochondria+during+cell+differentiation+and+aging&rft.pages=28&rft.pub=Deposited+Doc.+VINITI+19.09.85%2C+%E2%84%966756-%D0%9285&rft.date=1985&rft_id=http%3A%2F%2Faiexandr2010.narod.ru%2FBiogenesis.pdf&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-29"><span class="mw-cite-backlink"><b><a href="#cite_ref-29">^</a></b></span> <span class="reference-text">Miquel J, Economos AC, Fleming J, et al.<link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite class="citation cs2"><i>Mitochondrial role in cell aging</i>, Exp Gerontol, 15, 1980, pp. 575–591</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Mitochondrial+role+in+cell+aging&rft.pages=575-591&rft.pub=Exp+Gerontol%2C+15&rft.date=1980&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-30"><span class="mw-cite-backlink"><b><a href="#cite_ref-30">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFWeindruch1996" class="citation journal cs1">Weindruch, Richard (January 1996). "Calorie Restriction and Aging". <i>Scientific American</i>: 49–52.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Scientific+American&rft.atitle=Calorie+Restriction+and+Aging&rft.pages=49-52&rft.date=1996-01&rft.aulast=Weindruch&rft.aufirst=Richard&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-31"><span class="mw-cite-backlink"><b><a href="#cite_ref-31">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFPoovathingalGruberHalliwellGunawan2009" class="citation journal cs1">Poovathingal SK, Gruber J, Halliwell B, Gunawan R (2009). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771766">"Stochastic drift in mitochondrial DNA point mutations: a novel perspective ex silico"</a>. <i>PLOS Computational Biology</i>. <b>5</b> (11): e1000572. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2009PLSCB...5E0572P">2009PLSCB...5E0572P</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1371%2Fjournal.pcbi.1000572">10.1371/journal.pcbi.1000572</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771766">2771766</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19936024">19936024</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=PLOS+Computational+Biology&rft.atitle=Stochastic+drift+in+mitochondrial+DNA+point+mutations%3A+a+novel+perspective+ex+silico&rft.volume=5&rft.issue=11&rft.pages=e1000572&rft.date=2009&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2771766%23id-name%3DPMC&rft_id=info%3Apmid%2F19936024&rft_id=info%3Adoi%2F10.1371%2Fjournal.pcbi.1000572&rft_id=info%3Abibcode%2F2009PLSCB...5E0572P&rft.aulast=Poovathingal&rft.aufirst=SK&rft.au=Gruber%2C+J&rft.au=Halliwell%2C+B&rft.au=Gunawan%2C+R&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2771766&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-32"><span class="mw-cite-backlink"><b><a href="#cite_ref-32">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFConteNarindrasorasakSarkar1996" class="citation journal cs1">Conte D, Narindrasorasak S, Sarkar B (1996). <a rel="nofollow" class="external text" href="https://doi.org/10.1074%2Fjbc.271.9.5125">"<i>In vivo</i> and <i>in vitro</i> iron-replaced zinc finger generates free radicals and causes DNA damage"</a>. <i>The Journal of Biological Chemistry</i>. <b>271</b> (9): 5125–30. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1074%2Fjbc.271.9.5125">10.1074/jbc.271.9.5125</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/8617792">8617792</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=The+Journal+of+Biological+Chemistry&rft.atitle=In+vivo+and+in+vitro+iron-replaced+zinc+finger+generates+free+radicals+and+causes+DNA+damage&rft.volume=271&rft.issue=9&rft.pages=5125-30&rft.date=1996&rft_id=info%3Adoi%2F10.1074%2Fjbc.271.9.5125&rft_id=info%3Apmid%2F8617792&rft.aulast=Conte&rft.aufirst=D&rft.au=Narindrasorasak%2C+S&rft.au=Sarkar%2C+B&rft_id=https%3A%2F%2Fdoi.org%2F10.1074%252Fjbc.271.9.5125&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-autogenerated1-33"><span class="mw-cite-backlink"><b><a href="#cite_ref-autogenerated1_33-0">^</a></b></span> <span class="reference-text">Afanas'ev I. Signaling and Damaging Functions of Free Radicals in Aging-Free Radical Theory, Hormesis, and TOR. Aging And Disease. 2010;1(2) 75–88.</span> </li> <li id="cite_note-34"><span class="mw-cite-backlink"><b><a href="#cite_ref-34">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFPérezBokovVan_RemmenMele2009" class="citation journal cs1">Pérez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, et al. (2009). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789432">"Is the oxidative stress theory of aging dead?"</a>. <i>Biochimica et Biophysica Acta (BBA) - General Subjects</i>. <b>1790</b> (10): 1005–14. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.bbagen.2009.06.003">10.1016/j.bbagen.2009.06.003</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789432">2789432</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19524016">19524016</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Biochimica+et+Biophysica+Acta+%28BBA%29+-+General+Subjects&rft.atitle=Is+the+oxidative+stress+theory+of+aging+dead%3F&rft.volume=1790&rft.issue=10&rft.pages=1005-14&rft.date=2009&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2789432%23id-name%3DPMC&rft_id=info%3Apmid%2F19524016&rft_id=info%3Adoi%2F10.1016%2Fj.bbagen.2009.06.003&rft.aulast=P%C3%A9rez&rft.aufirst=VI&rft.au=Bokov%2C+A&rft.au=Van+Remmen%2C+H&rft.au=Mele%2C+J&rft.au=Ran%2C+Q&rft.au=Ikeno%2C+Y&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2789432&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-35"><span class="mw-cite-backlink"><b><a href="#cite_ref-35">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFYeeYangHekimi2014" class="citation journal cs1">Yee C, Yang W, Hekimi S (2014). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454526">"The Intrinsic Apoptosis Pathway Mediates the Pro-Longevity Response to Mitochondrial ROS in C. elegans"</a>. <i>Cell</i>. <b>157</b> (4): 897–909. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.cell.2014.02.055">10.1016/j.cell.2014.02.055</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454526">4454526</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/24813612">24813612</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Cell&rft.atitle=The+Intrinsic+Apoptosis+Pathway+Mediates+the+Pro-Longevity+Response+to+Mitochondrial+ROS+in+C.+elegans&rft.volume=157&rft.issue=4&rft.pages=897-909&rft.date=2014&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4454526%23id-name%3DPMC&rft_id=info%3Apmid%2F24813612&rft_id=info%3Adoi%2F10.1016%2Fj.cell.2014.02.055&rft.aulast=Yee&rft.aufirst=C&rft.au=Yang%2C+W&rft.au=Hekimi%2C+S&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4454526&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Brewer_GJ_2010_173–9-36"><span class="mw-cite-backlink">^ <a href="#cite_ref-Brewer_GJ_2010_173–9_36-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Brewer_GJ_2010_173–9_36-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Brewer_GJ_2010_173–9_36-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBrewer_GJ2010" class="citation journal cs1">Brewer GJ (2010). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826600">"Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories"</a>. <i>Experimental Gerontology</i>. <b>45</b> (3): 173–9. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.exger.2009.11.007">10.1016/j.exger.2009.11.007</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826600">2826600</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19945522">19945522</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Experimental+Gerontology&rft.atitle=Epigenetic+oxidative+redox+shift+%28EORS%29+theory+of+aging+unifies+the+free+radical+and+insulin+signaling+theories&rft.volume=45&rft.issue=3&rft.pages=173-9&rft.date=2010&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2826600%23id-name%3DPMC&rft_id=info%3Apmid%2F19945522&rft_id=info%3Adoi%2F10.1016%2Fj.exger.2009.11.007&rft.au=Brewer+GJ&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2826600&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Brink_TC,_Demetrius_L,_Lehrach_H,_Adjaye_J_2009_549–64-37"><span class="mw-cite-backlink">^ <a href="#cite_ref-Brink_TC,_Demetrius_L,_Lehrach_H,_Adjaye_J_2009_549–64_37-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Brink_TC,_Demetrius_L,_Lehrach_H,_Adjaye_J_2009_549–64_37-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBrinkDemetriusLehrachAdjaye2009" class="citation journal cs1">Brink TC, Demetrius L, Lehrach H, Adjaye J (2009). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730443">"Age-related transcriptional changes in gene expression in different organs of mice support the metabolic stability theory of aging"</a>. <i>Biogerontology</i>. <b>10</b> (5): 549–64. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1007%2Fs10522-008-9197-8">10.1007/s10522-008-9197-8</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730443">2730443</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19031007">19031007</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Biogerontology&rft.atitle=Age-related+transcriptional+changes+in+gene+expression+in+different+organs+of+mice+support+the+metabolic+stability+theory+of+aging&rft.volume=10&rft.issue=5&rft.pages=549-64&rft.date=2009&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2730443%23id-name%3DPMC&rft_id=info%3Apmid%2F19031007&rft_id=info%3Adoi%2F10.1007%2Fs10522-008-9197-8&rft.aulast=Brink&rft.aufirst=TC&rft.au=Demetrius%2C+L&rft.au=Lehrach%2C+H&rft.au=Adjaye%2C+J&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2730443&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-Glucose_Restriction-38"><span class="mw-cite-backlink"><b><a href="#cite_ref-Glucose_Restriction_38-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFSchulzZarseVoigtUrban2007" class="citation journal cs1">Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007). <a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.cmet.2007.08.011">"Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress"</a>. <i>Cell Metabolism</i>. <b>6</b> (4): 280–93. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.cmet.2007.08.011">10.1016/j.cmet.2007.08.011</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17908557">17908557</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Cell+Metabolism&rft.atitle=Glucose+restriction+extends+Caenorhabditis+elegans+life+span+by+inducing+mitochondrial+respiration+and+increasing+oxidative+stress&rft.volume=6&rft.issue=4&rft.pages=280-93&rft.date=2007&rft_id=info%3Adoi%2F10.1016%2Fj.cmet.2007.08.011&rft_id=info%3Apmid%2F17908557&rft.aulast=Schulz&rft.aufirst=TJ&rft.au=Zarse%2C+K&rft.au=Voigt%2C+A&rft.au=Urban%2C+N&rft.au=Birringer%2C+M&rft.au=Ristow%2C+M&rft_id=https%3A%2F%2Fdoi.org%2F10.1016%252Fj.cmet.2007.08.011&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-39"><span class="mw-cite-backlink"><b><a href="#cite_ref-39">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFSohalMockettOrr2002" class="citation journal cs1">Sohal R, Mockett R, Orr W (2002). "Mechanisms of aging: an appraisal of the oxidative stress hypothesis". <i>Free Radic Biol Med</i>. <b>33</b> (5): 575–86. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2FS0891-5849%2802%2900886-9">10.1016/S0891-5849(02)00886-9</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/12208343">12208343</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Free+Radic+Biol+Med&rft.atitle=Mechanisms+of+aging%3A+an+appraisal+of+the+oxidative+stress+hypothesis&rft.volume=33&rft.issue=5&rft.pages=575-86&rft.date=2002&rft_id=info%3Adoi%2F10.1016%2FS0891-5849%2802%2900886-9&rft_id=info%3Apmid%2F12208343&rft.aulast=Sohal&rft.aufirst=R&rft.au=Mockett%2C+R&rft.au=Orr%2C+W&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-40"><span class="mw-cite-backlink"><b><a href="#cite_ref-40">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFSohal_R2002" class="citation journal cs1">Sohal R (2002). "Role of oxidative stress and protein oxidation in the aging process". <i>Free Radic Biol Med</i>. <b>33</b> (1): 37–44. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2FS0891-5849%2802%2900856-0">10.1016/S0891-5849(02)00856-0</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/12086680">12086680</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Free+Radic+Biol+Med&rft.atitle=Role+of+oxidative+stress+and+protein+oxidation+in+the+aging+process&rft.volume=33&rft.issue=1&rft.pages=37-44&rft.date=2002&rft_id=info%3Adoi%2F10.1016%2FS0891-5849%2802%2900856-0&rft_id=info%3Apmid%2F12086680&rft.au=Sohal+R&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-41"><span class="mw-cite-backlink"><b><a href="#cite_ref-41">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRattan_S2006" class="citation journal cs1">Rattan S (2006). "Theories of biological aging: genes, proteins, and free radicals". <i>Free Radic Res</i>. <b>40</b> (12): 1230–8. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1080%2F10715760600911303">10.1080/10715760600911303</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17090411">17090411</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:11125090">11125090</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Free+Radic+Res&rft.atitle=Theories+of+biological+aging%3A+genes%2C+proteins%2C+and+free+radicals&rft.volume=40&rft.issue=12&rft.pages=1230-8&rft.date=2006&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A11125090%23id-name%3DS2CID&rft_id=info%3Apmid%2F17090411&rft_id=info%3Adoi%2F10.1080%2F10715760600911303&rft.au=Rattan+S&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span></span> </li> <li id="cite_note-42"><span class="mw-cite-backlink"><b><a href="#cite_ref-42">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBjelakovicNikolovaGluudSimonetti2007" class="citation journal cs1">Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". <i>The Journal of the American Medical Association</i>. <b>297</b> (8): 842–57. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1001%2Fjama.297.8.842">10.1001/jama.297.8.842</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17327526">17327526</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=The+Journal+of+the+American+Medical+Association&rft.atitle=Mortality+in+randomized+trials+of+antioxidant+supplements+for+primary+and+secondary+prevention%3A+systematic+review+and+meta-analysis&rft.volume=297&rft.issue=8&rft.pages=842-57&rft.date=2007&rft_id=info%3Adoi%2F10.1001%2Fjama.297.8.842&rft_id=info%3Apmid%2F17327526&rft.aulast=Bjelakovic&rft.aufirst=G&rft.au=Nikolova%2C+D&rft.au=Gluud%2C+LL&rft.au=Simonetti%2C+RG&rft.au=Gluud%2C+C&rfr_id=info%3Asid%2Fen.wikipedia.org%3AFree-radical+theory+of+aging" class="Z3988"></span>.</span> </li> <li id="cite_note-Montgomery-43"><span class="mw-cite-backlink">^ <a href="#cite_ref-Montgomery_43-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Montgomery_43-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMontgomeryHulbertButtemer2012" class="citation journal cs1">Montgomery MK, Hulbert AJ, Buttemer WA (2012). "Does the oxidative stress theory of aging explain longevity differences in birds? I. Mitochondrial ROS production". <i>Exp. Gerontol</i>. <b>47</b> (3): 203–10. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.exger.2011.11.006">10.1016/j.exger.2011.11.006</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22123429">22123429</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:984298">984298</a>.</cite><span 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