Editing Reactive oxygen species (section)

==Cause of aging==
According to the [[free radical theory of aging]], oxidative damage initiated by reactive oxygen species is a major contributor to the functional decline that is characteristic of aging. While studies in invertebrate models indicate that animals genetically engineered to lack specific antioxidant enzymes (such as SOD), in general, show a shortened lifespan (as one would expect from the theory), the converse manipulation, increasing the levels of antioxidant enzymes, has yielded inconsistent effects on lifespan (though some studies in ''[[Drosophila]]'' do show that lifespan can be increased by the overexpression of MnSOD or glutathione biosynthesizing enzymes). Also contrary to this theory, deletion of [[SOD2|mitochondrial SOD2]] can extend lifespan in ''[[Caenorhabditis elegans]]''.<ref name="pmid19197346">{{Cite journal |vauthors=Van Raamsdonk JM, Hekimi S |date=February 2009 |title=Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans |journal=PLOS Genetics |volume=5 |issue=2 |pages=e1000361 |doi=10.1371/journal.pgen.1000361 |pmc=2628729 |pmid=19197346 |doi-access=free}}</ref>

In mice, the story is somewhat similar. Deleting antioxidant enzymes, in general, yields shorter lifespan, although overexpression studies have not (with some exceptions) consistently extended lifespan.<ref name="pmid17640558">{{Cite journal |vauthors=Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H |date=August 2007 |title=Trends in oxidative aging theories |journal=Free Radical Biology & Medicine |volume=43 |issue=4 |pages=477–503 |doi=10.1016/j.freeradbiomed.2007.03.034 |pmid=17640558}}</ref> Study of a rat model of premature [[ageing|aging]] found increased [[oxidative stress]], reduced [[antioxidant]] enzyme activity and substantially greater [[DNA damage (naturally occurring)|DNA damage]] in the brain [[neocortex]] and [[hippocampus]] of the prematurely aged rats than in normally aging control rats.<ref name="pmid24709042">{{Cite journal |vauthors=Sinha JK, Ghosh S, Swain U, Giridharan NV, Raghunath M |date=June 2014 |title=Increased macromolecular damage due to oxidative stress in the neocortex and hippocampus of WNIN/Ob, a novel rat model of premature aging |journal=Neuroscience |volume=269 |pages=256–264 |doi=10.1016/j.neuroscience.2014.03.040 |pmid=24709042 |s2cid=9934178}}</ref> The DNA damage [[8-Oxo-2'-deoxyguanosine|8-OHdG]] is a product of ROS interaction with DNA. Numerous studies have shown that [[8-Oxo-2'-deoxyguanosine|8-OHdG]] increases with age<ref>{{Cite book |title=New Research on DNA Damages |vauthors=Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K |date=2008 |publisher=[[Nova Science Publishers, Inc.]] |isbn=978-1-60456-581-2 |veditors=Kimura H, Suzuki A |location=New York |pages=1–47 |chapter=Chapter 1: Cancer and aging as consequences of un-repaired DNA damage. |access-date=2018-03-15 |chapter-url=https://www.novapublishers.com/catalog/product_info.php?products_id=43247 |archive-url=https://web.archive.org/web/20141025091740/https://www.novapublishers.com/catalog/product_info.php?products_id=43247 |archive-date=2014-10-25 |url-status=dead}}{{open access}}, but read only.</ref> (see [[DNA damage theory of aging]]).