Editing Free-radical theory of aging (section)

== Background ==
The free radical theory of aging was conceived by [[Denham Harman]] in the 1950s, when prevailing scientific opinion held that free radicals were too unstable to exist in biological systems.<ref name="ReferenceC">{{cite journal | author = Harman D | date = Jul 1956 | title = Aging: a theory based on free radical and radiation chemistry | journal = J Gerontol | volume = 11 | issue = 3| pages = 298–300 | doi=10.1093/geronj/11.3.298 | pmid=13332224| hdl = 2027/mdp.39015086547422 | hdl-access = free }}</ref>  This was also before anyone invoked free radicals as a cause of degenerative diseases.<ref name="Harman D 2009">{{cite journal | author = Harman D | year = 2009 | title = Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009 | journal = Biogerontology | volume = 10 | issue = 6| pages = 773–81 | doi=10.1007/s10522-009-9234-2| pmid = 19466577 | s2cid = 13512659 }}</ref> Two sources inspired Harman: 1) the [[rate of living theory]], which holds that lifespan is an inverse function of metabolic rate which in turn is proportional to oxygen consumption, and 2) [[Rebeca Gerschman]]'s observation that hyperbaric oxygen toxicity and [[radiation toxicity]] could be explained by the same underlying phenomenon: oxygen free radicals.<ref name="ReferenceC"/><ref name="Speakman JR, Selman C 2011 255–9">{{cite journal |vauthors=Speakman JR, Selman C | year = 2011 | title = The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan | journal = BioEssays | volume = 33 | issue = 4| pages = 255–9 | doi=10.1002/bies.201000132 | pmid=21290398| s2cid = 13720843 }}</ref> 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.<ref name="ReferenceC"/><ref name="Speakman JR, Selman C 2011 255–9"/>

In later years, the free radical theory was expanded to include not only aging ''per se'', but also age-related diseases.<ref name="Harman D 2009"/> Free radical damage within cells has been linked to a range of disorders including [[cancer]], [[arthritis]], [[atherosclerosis]], [[Alzheimer's disease]], and [[diabetes]].<ref>Clancy D, Birdsall J. Flies, worms and the Free Radical Theory of ageing. Ageing Research Reviews. (0).</ref> 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 [[apoptosis]] and in extreme cases [[necrosis]].<ref>{{cite journal |vauthors=Chatterjee S, Lardinois O, Bhattacharjee S, Tucker J, Corbett J, Deterding L | year = 2011 | title = 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 | journal = Free Radical Biology and Medicine | volume = 50 | issue = 8| pages = 988–99 | doi=10.1016/j.freeradbiomed.2010.12.037| pmid = 21215311 |display-authors=etal| pmc=3051032}}</ref>

In 1972, Harman modified his original theory.<ref name="Harman D 2009"/> In its current form, this theory proposes that [[reactive oxygen species]] (ROS) that are produced in the [[mitochondria]], causes damage to certain [[macromolecules]] including [[lipids]], [[proteins]] and most importantly mitochondrial DNA.<ref name="Jang YC, Remmen HV 2009 256–60">{{cite journal |vauthors=Jang YC, Remmen HV | year = 2009 | title = The mitochondrial theory of aging: Insight from transgenic and knockout mouse models | journal = Experimental Gerontology | volume = 44 | issue = 4| pages = 256–60 | doi=10.1016/j.exger.2008.12.006| pmid = 19171187 | s2cid = 19815246 }}</ref> This damage then causes mutations which lead to an increase of ROS production and greatly enhance the accumulation of free radicals within cells.<ref name="Jang YC, Remmen HV 2009 256–60"/> This mitochondrial theory has been more widely accepted that it could play a major role in contributing to the aging process.<ref name="Gruber J, Schaffer S, Halliwell B 2008 6554–79">{{cite journal |vauthors=Gruber J, Schaffer S, Halliwell B | year = 2008 | title = The mitochondrial free radical theory of ageing—where do we stand? | journal = Frontiers in Bioscience | volume = 13 | issue = 13| pages = 6554–79 | doi=10.2741/3174| pmid = 18508680 | doi-access = free }}</ref>

Since Harman first proposed the free radical theory of aging, there have been continual modifications and extensions to his original theory.<ref name="Gruber J, Schaffer S, Halliwell B 2008 6554–79"/>