Editing Mitochondrial DNA (section)

===Relationship with ageing===
Though the idea is controversial, some evidence suggests a link between aging and mitochondrial genome dysfunction.<ref>{{Cite book |url=http://www.sens.org/files/pdf/MiFRA-06.pdf |title=The Mitochondrial Free Radical Theory of Aging |vauthors=de Grey A |publisher=Landes Bioscience |year=1999 |isbn=978-1-57059-564-6 |access-date=1 May 2016 |archive-url=https://web.archive.org/web/20160603015443/http://www.sens.org/files/pdf/MiFRA-06.pdf |archive-date=3 June 2016 |url-status=live}}{{page needed|date=April 2015}}</ref> In essence, mutations in mtDNA upset a careful balance of [[reactive oxygen species]] (ROS) production and enzymatic ROS scavenging (by enzymes like [[superoxide dismutase]], [[catalase]], [[glutathione peroxidase]] and others). However, some mutations that increase ROS production (e.g., by reducing antioxidant defenses) in worms increase, rather than decrease, their longevity.<ref name=pmid19796285/> Also, [[Naked mole-rat|naked mole rats]], [[rodent]]s about the size of [[Mouse|mice]], live about eight times longer than mice despite having reduced, compared to mice, antioxidant defenses and increased oxidative damage to biomolecules.<ref>{{Cite journal |vauthors=Lewis KN, Andziak B, Yang T, Buffenstein R |date=October 2013 |title=The naked mole-rat response to oxidative stress: just deal with it |journal=Antioxidants & Redox Signaling |volume=19 |issue=12 |pages=1388–1399 |doi=10.1089/ars.2012.4911 |pmc=3791056 |pmid=23025341}}</ref> Once, there was thought to be a positive feedback loop at work (a 'Vicious Cycle'); as mitochondrial DNA accumulates genetic damage caused by free radicals, the mitochondria lose function and leak free radicals into the [[cytosol]]. A decrease in mitochondrial function reduces overall metabolic efficiency.<ref>{{Cite journal |vauthors=Shigenaga MK, Hagen TM, Ames BN |date=November 1994 |title=Oxidative damage and mitochondrial decay in aging |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=91 |issue=23 |pages=10771–10778 |bibcode=1994PNAS...9110771S |doi=10.1073/pnas.91.23.10771 |jstor=2365473 |pmc=45108 |pmid=7971961 |doi-access=free}}</ref> However, this concept was conclusively disproved when it was demonstrated that mice, which were genetically altered to accumulate mtDNA mutations at an accelerated rate to age prematurely, but their tissues do not produce more ROS as predicted by the 'Vicious Cycle' hypothesis.<ref>{{Cite journal |display-authors=6 |vauthors=Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, Spelbrink JN, Wibom R, Jacobs HT, Larsson NG |date=December 2005 |title=Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=102 |issue=50 |pages=17993–17998 |bibcode=2005PNAS..10217993T |doi=10.1073/pnas.0508886102 |jstor=4152716 |pmc=1312403 |pmid=16332961 |doi-access=free}}</ref> Supporting a link between longevity and mitochondrial DNA, some studies have found correlations between biochemical properties of the mitochondrial DNA and the longevity of species.<ref>{{Cite journal |vauthors=Aledo JC, Li Y, de Magalhães JP, Ruíz-Camacho M, Pérez-Claros JA |date=April 2011 |title=Mitochondrially encoded methionine is inversely related to longevity in mammals |journal=Aging Cell |volume=10 |issue=2 |pages=198–207 |doi=10.1111/j.1474-9726.2010.00657.x |pmid=21108730 |doi-access=free}}</ref> The application of a mitochondrial-specific ROS scavenger, which lead to a significant longevity of the mice studied,<ref>{{Cite journal |display-authors=6 |vauthors=Shabalina IG, Vyssokikh MY, Gibanova N, Csikasz RI, Edgar D, Hallden-Waldemarson A, Rozhdestvenskaya Z, Bakeeva LE, Vays VB, Pustovidko AV, Skulachev MV, Cannon B, Skulachev VP, Nedergaard J |date=February 2017 |title=Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1 |journal=Aging |volume=9 |issue=2 |pages=315–339 |doi=10.18632/aging.101174 |pmc=5361666 |pmid=28209927}}</ref> suggests that mitochondria may still be well-implicated in ageing. Extensive research is being conducted to further investigate this link and methods to combat ageing. Presently, [[gene therapy]] and [[nutraceutical]] supplementation are popular areas of ongoing research.<ref>{{Cite journal |vauthors=Ferrari CK |year=2004 |title=Functional foods, herbs and nutraceuticals: towards biochemical mechanisms of healthy aging |journal=Biogerontology |volume=5 |issue=5 |pages=275–289 |doi=10.1007/s10522-004-2566-z |pmid=15547316 |s2cid=11568208}}</ref><ref>{{Cite journal |vauthors=Taylor RW |date=February 2005 |title=Gene therapy for the treatment of mitochondrial DNA disorders |journal=Expert Opinion on Biological Therapy |volume=5 |issue=2 |pages=183–194 |doi=10.1517/14712598.5.2.183 |pmid=15757380 |s2cid=35276183}}</ref> Bjelakovic et al. analyzed the results of 78 studies between 1977 and 2012, involving a total of 296,707 participants, and concluded that antioxidant supplements do not reduce all-cause mortality nor extend lifespan, while some of them, such as beta carotene, vitamin E, and higher doses of vitamin A, may actually increase mortality.<ref>{{Cite journal |vauthors=Bjelakovic G, Nikolova D, Gluud C |date=September 2013 |title=Antioxidant supplements to prevent mortality |journal=JAMA |volume=310 |issue=11 |pages=1178–1179 |doi=10.1001/jama.2013.277028 |pmid=24045742}}</ref>
In a recent study, it was shown that dietary restriction can reverse ageing alterations by affecting the accumulation of mtDNA damage in several organs of rats. For example, dietary restriction prevented age-related accumulation of mtDNA damage in the cortex and decreased it in the lung and testis.<ref>{{Cite journal |display-authors=6 |vauthors=Gureev AP, Andrianova NV, Pevzner IB, Zorova LD, Chernyshova EV, Sadovnikova IS, Chistyakov DV, Popkov VA, Semenovich DS, Babenko VA, Silachev DN, Zorov DB, Plotnikov EY, Popov VN |date=September 2022 |title=Dietary restriction modulates mitochondrial DNA damage and oxylipin profile in aged rats |url=https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.16451 |journal=The FEBS Journal |volume=289 |issue=18 |pages=5697–5713 |doi=10.1111/febs.16451 |pmid=35373508 |s2cid=247938550 |url-access=subscription |archive-url=https://web.archive.org/web/20220504105319/https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.16451 |archive-date=4 May 2022 |access-date=11 May 2022}}</ref>