Editing Caenorhabditis elegans (section)

=== Ageing ===
''C. elegans'' has been a model organism for research into [[ageing]]; for example, the inhibition of an [[insulin-like growth factor]] signaling pathway has been shown to increase adult lifespan threefold;<ref>{{cite journal | vauthors = Wolkow CA, Kimura KD, Lee MS, Ruvkun G | title = Regulation of C. elegans life-span by insulinlike signaling in the nervous system | journal = Science | volume = 290 | issue = 5489 | pages = 147–50 | date = October 2000 | pmid = 11021802 | doi = 10.1126/science.290.5489.147 | bibcode = 2000Sci...290..147W }}</ref><ref>{{cite journal | vauthors = Ewald CY, Landis JN, Porter Abate J, Murphy CT, Blackwell TK | title = Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity | language = En | journal = Nature | volume = 519 | issue = 7541 | pages = 97–101 | date = March 2015 | pmid = 25517099 | pmc = 4352135 | doi = 10.1038/nature14021 | bibcode = 2015Natur.519...97E }}</ref> while glucose feeding promotes oxidative stress and reduces adult lifespan by a half.<ref name="ReferenceC"/> Similarly, induced degradation of an insulin/IGF-1 receptor late in life extended life expectancy of worms dramatically.<ref>{{Cite journal|last1=Venz|first1=Richard|last2=Pekec|first2=Tina|last3=Katic|first3=Iskra|last4=Ciosk|first4=Rafal|author5-link=Collin Y. Ewald|last5=Ewald|first5=Collin Yvès|date=2021-09-10|editor-last=Leiser|editor-first=Scott F|editor2-last=Kaeberlein|editor2-first=Matt|editor3-last=Alcedo|editor3-first=Joy|title=End-of-life targeted degradation of DAF-2 insulin/IGF-1 receptor promotes longevity free from growth-related pathologies|journal=eLife|volume=10|pages=e71335|doi=10.7554/eLife.71335|pmid=34505574|pmc=8492056|issn=2050-084X |doi-access=free }}</ref> 
Long-lived [[mutant]]s of ''C. elegans'' were demonstrated to be resistant to [[oxidative stress]] and [[ultraviolet|UV light]].<ref name="Hyun2008">{{Cite journal |doi=10.1093/nar/gkm1161 |pmc=2275101 |pmid=18203746|title=Longevity and resistance to stress correlate with DNA repair capacity in Caenorhabditis elegans |year=2008 |last1=Hyun |first1=Moonjung |last2=Lee |first2=Jihyun |last3=Lee |first3=Kyungjin |last4=May |first4=Alfred |last5=Bohr |first5=Vilhelm A. |last6=Ahn |first6=Byungchan |journal=Nucleic Acids Research |volume=36 |issue=4 |pages=1380–1389 }}</ref> These long-lived mutants had a higher [[DNA repair]] capability than wild-type ''C. elegans''.<ref name = Hyun2008/> Knockdown of the [[nucleotide excision repair]] gene Xpa-1 increased sensitivity to UV and reduced the [[longevity|life span]] of the long-lived mutants. These findings indicate that [[DNA damage theory of aging|DNA repair capability underlies longevity]].  Consistent with the idea that oxidative DNA damage causes aging, it was found that in ''C. elegans'', [[exosome (vesicle)|exosome]]-mediated delivery of [[superoxide dismutase]] (SOD) reduces the level of [[reactive oxygen species]] (ROS) and significantly extends lifespan, i.e. delays aging under normal, as well as hostile conditions.<ref>{{cite journal |vauthors=Shao X, Zhang M, Chen Y, Sun S, Yang S, Li Q |title=Exosome-mediated delivery of superoxide dismutase for anti-aging studies in Caenorhabditis elegans |journal=Int J Pharm |volume=641 |issue= |pages=123090 |date=June 2023 |pmid=37268030 |doi=10.1016/j.ijpharm.2023.123090 |url=}}</ref>

The capacity to repair DNA damage by the process of nucleotide excision repair declines with age.<ref>{{Cite journal |doi=10.1186/gb-2007-8-5-r70 |pmc=1929140 |pmid=17472752|title=Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans |year=2007 |last1=Meyer |first1=Joel N. |last2=Boyd |first2=Windy A. |last3=Azzam |first3=Gregory A. |last4=Haugen |first4=Astrid C. |last5=Freedman |first5=Jonathan H. |last6=Van Houten |first6=Bennett |journal=Genome Biology |volume=8 |issue=5 |pages=R70 |doi-access=free }}</ref>

''C. elegans'' exposed to 5mM [[lithium chloride]] (LiCl) showed lengthened life spans.<ref>{{cite journal | vauthors = McColl G, Killilea DW, Hubbard AE, Vantipalli MC, Melov S, Lithgow GJ | title = Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans | journal = The Journal of Biological Chemistry | volume = 283 | issue = 1 | pages = 350–7 | date = January 2008 | pmid = 17959600 | pmc = 2739662 | doi = 10.1074/jbc.M705028200 | doi-access = free }}</ref> When exposed to 10μM LiCl, reduced mortality was observed, but not with 1μM.<ref>{{cite journal | vauthors = Zarse K, Terao T, Tian J, Iwata N, Ishii N, Ristow M | title = Low-dose lithium uptake promotes longevity in humans and metazoans | journal = European Journal of Nutrition | volume = 50 | issue = 5 | pages = 387–9 | date = August 2011 | pmid = 21301855 | pmc = 3151375 | doi = 10.1007/s00394-011-0171-x }}</ref>

''C. elegans'' has been instrumental in the identification of the functions of genes implicated in [[Alzheimer's disease]], such as [[PSEN1|presenilin]].<ref>{{cite journal | vauthors = Ewald CY, Li C | title = Understanding the molecular basis of Alzheimer's disease using a Caenorhabditis elegans model system | journal = Brain Structure & Function | volume = 214 | issue = 2–3 | pages = 263–83 | date = March 2010 | pmid = 20012092 | pmc = 3902020 | doi = 10.1007/s00429-009-0235-3 }}</ref> Moreover, extensive research on ''C. elegans'' has identified [[RNA-binding protein]]s as essential factors during germline and early embryonic development.<ref>{{cite journal | vauthors = Hanazawa M, Yonetani M, Sugimoto A | title = PGL proteins self associate and bind RNPs to mediate germ granule assembly in C. elegans | journal = The Journal of Cell Biology | volume = 192 | issue = 6 | pages = 929–37 | date = March 2011 | pmid = 21402787 | pmc = 3063142 | doi = 10.1083/jcb.201010106 }}</ref>

[[Telomere]]s, the length of which have been shown to correlate with increased lifespan and delayed onset of [[senescence]] in a multitude of organisms, from ''C. elegans''<ref>{{Cite journal|last1=Coutts|first1=Fiona|last2=Palmos|first2=Alish B.|last3=Duarte|first3=Rodrigo R. R.|last4=de Jong|first4=Simone|last5=Lewis|first5=Cathryn M.|last6=Dima|first6=Danai|last7=Powell|first7=Timothy R.|date=March 2019|title=The polygenic nature of telomere length and the anti-ageing properties of lithium|journal=Neuropsychopharmacology|volume=44|issue=4|pages=757–765|doi=10.1038/s41386-018-0289-0|issn=1740-634X|pmc=6372618|pmid=30559463}}</ref><ref>{{Cite journal|last1=Raices|first1=Marcela|last2=Maruyama|first2=Hugo|last3=Dillin|first3=Andrew|last4=Karlseder|first4=Jan|date=September 2005|title=Uncoupling of longevity and telomere length in C. elegans|journal=PLOS Genetics|volume=1|issue=3|pages=e30|doi=10.1371/journal.pgen.0010030|issn=1553-7404|pmc=1200426|pmid=16151516 |doi-access=free }}</ref> to humans,<ref>{{Cite journal|last1=Lulkiewicz|first1=M.|last2=Bajsert|first2=J.|last3=Kopczynski|first3=P.|last4=Barczak|first4=W.|last5=Rubis|first5=B.|date=September 2020|title=Telomere length: how the length makes a difference|journal=Molecular Biology Reports|volume=47|issue=9|pages=7181–7188|doi=10.1007/s11033-020-05551-y|issn=1573-4978|pmc=7561533|pmid=32876842}}</ref> show an interesting behaviour in ''C. elegans.'' While ''C. elegans'' maintains its telomeres in a canonical way similar to other eukaryotes, in contrast ''[[Drosophila melanogaster]]'' is noteworthy in its use of [[retrotransposon]]s to maintain its telomeres,<ref>{{Cite journal|last1=Pardue|first1=Mary-Lou|last2=DeBaryshe|first2=P. G.|date=2011-12-20|title=Retrotransposons that maintain chromosome ends|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=108|issue=51|pages=20317–20324|doi=10.1073/pnas.1100278108|issn=1091-6490|pmc=3251079|pmid=21821789|doi-access=free}}</ref> during [[Gene knockout|knock-out]] of the [[Telomerase reverse transcriptase|catalytic subunit of the telomerase (''trt-1'')]] ''C. elegans'' can gain the ability of alternative telomere lengthening (ALT). ''C. elegans'' was the first eukaryote to gain ALT functionality after knock-out of the canonical [[telomerase]] pathway.<ref>{{Cite journal|last1=Meier|first1=Bettina|last2=Clejan|first2=Iuval|last3=Liu|first3=Yan|last4=Lowden|first4=Mia|last5=Gartner|first5=Anton|last6=Hodgkin|first6=Jonathan|last7=Ahmed|first7=Shawn|date=February 2006|title=trt-1 is the Caenorhabditis elegans catalytic subunit of telomerase|journal=PLOS Genetics|volume=2|issue=2|pages=e18|doi=10.1371/journal.pgen.0020018|issn=1553-7404|pmc=1361356|pmid=16477310 |doi-access=free }}</ref> ALT is also observed in about 10-15% of all clinical cancers.<ref>{{Cite journal|last1=Cesare|first1=Anthony J.|last2=Reddel|first2=Roger R.|date=May 2010|title=Alternative lengthening of telomeres: models, mechanisms and implications|url=https://pubmed.ncbi.nlm.nih.gov/20351727|journal=Nature Reviews. Genetics|volume=11|issue=5|pages=319–330|doi=10.1038/nrg2763|issn=1471-0064|pmid=20351727|s2cid=19224032}}</ref> Thus ''C. elegans'' is a prime candidate for ALT research.<ref>{{Cite journal|last1=Ijomone|first1=Omamuyovwi M.|last2=Miah|first2=Mahfuzur R.|last3=Peres|first3=Tanara V.|last4=Nwoha|first4=Polycarp U.|last5=Aschner|first5=Michael|date=December 2016|title=Null allele mutants of trt-1, the catalytic subunit of telomerase in Caenorhabditis elegans, are less sensitive to Mn-induced toxicity and DAergic degeneration|url=https://pubmed.ncbi.nlm.nih.gov/27593554|journal=Neurotoxicology|volume=57|pages=54–60|doi=10.1016/j.neuro.2016.08.016|issn=1872-9711|pmid=27593554|bibcode=2016NeuTx..57...54I }}</ref><ref>{{Cite journal|last1=Shtessel|first1=Ludmila|last2=Lowden|first2=Mia Rochelle|last3=Cheng|first3=Chen|last4=Simon|first4=Matt|last5=Wang|first5=Kyle|last6=Ahmed|first6=Shawn|date=February 2013|title=Caenorhabditis elegans POT-1 and POT-2 repress telomere maintenance pathways|journal=G3: Genes, Genomes, Genetics|volume=3|issue=2|pages=305–313|doi=10.1534/g3.112.004440|issn=2160-1836|pmc=3564990|pmid=23390606}}</ref><ref>{{Cite journal|last1=Kwon|first1=Mi-Sun|last2=Min|first2=Jaewon|last3=Jeon|first3=Hee-Yeon|last4=Hwang|first4=Kwangwoo|last5=Kim|first5=Chuna|last6=Lee|first6=Junho|last7=Joung|first7=Je-Gun|last8=Park|first8=Woong-Yang|last9=Lee|first9=Hyunsook|date=October 2016|title=Paradoxical delay of senescence upon depletion of BRCA2 in telomerase-deficient worms|journal=FEBS Open Bio|volume=6|issue=10|pages=1016–1024|doi=10.1002/2211-5463.12109|issn=2211-5463|pmc=5055038|pmid=27761361}}</ref> Bayat et al. showed the paradoxical shortening of telomeres during ''[[Telomerase reverse transcriptase|trt-1]]'' [[over-expression]] which lead to near [[Sterility (physiology)|sterility]] while the worms even exhibited a slight increase in lifespan, despite shortened telomeres.<ref>{{Cite journal|last1=Bayat|first1=Melih|last2=Tanny|first2=Robyn E.|last3=Wang|first3=Ye|last4=Herden|first4=Carla|last5=Daniel|first5=Jens|last6=Andersen|first6=Erik C.|last7=Liebau|first7=Eva|last8=Waschk|first8=Daniel E. J.|date=2020-03-30|title=Effects of telomerase overexpression in the model organism Caenorhabditis elegans|url=https://pubmed.ncbi.nlm.nih.gov/31954861|journal=Gene|volume=732|pages=144367|doi=10.1016/j.gene.2020.144367|issn=1879-0038|pmid=31954861|s2cid=210829489}}</ref>