Editing Mitochondrion (section)

===Relationships to aging===
{{See also|Hallmarks of aging#Mitochondrial dysfunction}}

There may be some leakage of the [[Electron transport chain|electrons transferred]] in the respiratory chain to form [[reactive oxygen species]]. This was thought to result in significant [[oxidative stress]] in the mitochondria with high mutation rates of mitochondrial DNA.<ref>{{cite journal | vauthors = Richter C, Park JW, Ames BN | title = Normal oxidative damage to mitochondrial and nuclear DNA is extensive | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 17 | pages = 6465–6467 | date = September 1988 | pmid = 3413108 | pmc = 281993 | doi = 10.1073/pnas.85.17.6465 | doi-access = free | bibcode = 1988PNAS...85.6465R }}</ref> Hypothesized links between aging and oxidative stress are not new and were proposed in 1956,<ref>{{cite journal | vauthors = Harman D | title = Aging: a theory based on free radical and radiation chemistry | journal = Journal of Gerontology | volume = 11 | issue = 3 | pages = 298–300 | date = July 1956 | pmid = 13332224 | doi = 10.1093/geronj/11.3.298 | citeseerx = 10.1.1.663.3809 }}</ref> which was later refined into the [[Mitochondrial theory of ageing|mitochondrial free radical theory of aging]].<ref>{{cite journal | vauthors = Harman D | title = The biologic clock: the mitochondria? | journal = Journal of the American Geriatrics Society | volume = 20 | issue = 4 | pages = 145–147 | date = April 1972 | pmid = 5016631 | doi = 10.1111/j.1532-5415.1972.tb00787.x }}</ref> A vicious cycle was thought to occur, as oxidative stress leads to mitochondrial DNA mutations, which can lead to enzymatic abnormalities and further oxidative stress.

A number of changes can occur to mitochondria during the aging process.<ref>{{cite web |url= http://www.circuitblue.com/biogerontology/mito.shtml |title= Mitochondria and Aging |publisher= circuitblue.co |access-date= October 23, 2006 |archive-date= September 29, 2017 |archive-url= https://web.archive.org/web/20170929210338/http://circuitblue.com/biogerontology/mito.shtml |url-status= live }}</ref> Tissues from elderly humans show a decrease in enzymatic activity of the proteins of the respiratory chain.<ref>{{cite journal | vauthors = Boffoli D, Scacco SC, Vergari R, Solarino G, Santacroce G, Papa S | title = Decline with age of the respiratory chain activity in human skeletal muscle | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1226 | issue = 1 | pages = 73–82 | date = April 1994 | pmid = 8155742 | doi = 10.1016/0925-4439(94)90061-2 }}</ref> However, mutated mtDNA can only be found in about 0.2% of very old cells.<ref>{{cite journal | vauthors = de Grey AD | title = Mitochondrial mutations in mammalian aging: an over-hasty about-turn? | journal = Rejuvenation Research | volume = 7 | issue = 3 | pages = 171–174 | year = 2004 | pmid = 15588517 | doi = 10.1089/rej.2004.7.171 }}</ref> Large deletions in the mitochondrial genome have been hypothesized to lead to high levels of [[oxidative stress]] and neuronal death in [[Parkinson's disease]].<ref>{{cite journal | vauthors = Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM | title = High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease | journal = Nature Genetics | volume = 38 | issue = 5 | pages = 515–517 | date = May 2006 | pmid = 16604074 | doi = 10.1038/ng1769 }}</ref> Mitochondrial dysfunction has also been shown to occur in [[amyotrophic lateral sclerosis]].<ref>{{cite journal | vauthors = Mehta AR, Walters R, Waldron FM, Pal S, Selvaraj BT, Macleod MR, Hardingham GE, Chandran S, Gregory JM | title = Targeting mitochondrial dysfunction in amyotrophic lateral sclerosis: a systematic review and meta-analysis | journal = Brain Communications | volume = 1 | issue = 1 | pages = fcz009 | date = August 2019 | pmid = 32133457 | pmc = 7056361 | doi = 10.1093/braincomms/fcz009 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Mehta AR, Gregory JM, Dando O, Carter RN, Burr K, Nanda J, Story D, McDade K, Smith C, Morton NM, Mahad DJ, Hardingham GE, Chandran S, Selvaraj BT | title = Mitochondrial bioenergetic deficits in C9orf72 amyotrophic lateral sclerosis motor neurons cause dysfunctional axonal homeostasis | journal = Acta Neuropathologica | volume = 141 | issue = 2 | pages = 257–279 | date = February 2021 | pmid = 33398403 | pmc = 7847443 | doi = 10.1007/s00401-020-02252-5 | doi-access = free }}</ref>

Since mitochondria cover a pivotal role in the ovarian function, by providing ATP necessary for the development from germinal vesicle to mature [[oocyte]], a decreased mitochondria function can lead to inflammation, resulting in premature ovarian failure and accelerated ovarian aging. The resulting dysfunction is then reflected in quantitative (such as mtDNA copy number and mtDNA deletions), qualitative (such as mutations and strand breaks) and oxidative damage (such as dysfunctional mitochondria due to ROS), which are not only relevant in ovarian aging, but perturb oocyte-cumulus crosstalk in the ovary, are linked to genetic disorders (such as Fragile X) and can interfere with embryo selection.<ref>{{cite journal | vauthors = Chiang JL, Shukla P, Pagidas K, Ahmed NS, Karri S, Gunn DD, Hurd WW, Singh KK | title = Mitochondria in Ovarian Aging and Reproductive Longevity | journal = Ageing Research Reviews | volume = 63 | pages = 101168 | date = November 2020 | pmid = 32896666 | pmc = 9375691 | doi = 10.1016/j.arr.2020.101168 }}</ref>