Biological immortality#Cell lines

{{short description|State in which the rate of mortality from senescence is stable or decreasing}}

Biological immortality (sometimes referred to as bio-indefinite mortality) is a state in which the rate of mortality from senescence (or aging) is stable or decreasing, thus decoupling it from chronological age. Various unicellular and multicellular species, including some vertebrates, achieve this state either throughout their existence or after living long enough. A biologically immortal living being can still die from means other than senescence, such as through injury, poison, disease, predation, lack of available resources, or changes to environment.

This definition of immortality has been challenged in the Handbook of the Biology of Aging,{{Cite book |last=Masoro |first=E.J. |title=Handbook of the Biology of Aging |publisher=Academic Press |year=2006 |isbn=978-0-12-088387-5 |editor-last=Austad, S.N. |edition=Sixth |location=San Diego, CA}} because the increase in rate of mortality as a function of chronological age may be negligible at extremely old ages, an idea referred to as the late-life mortality plateau. The rate of mortality may cease to increase in old age, but in most cases that rate is typically very high.{{Cite journal |last1=Michael R. Rose |last2=Casandra L. Rauser |last3=Laurence D. Mueller |date=Nov–Dec 2005 |title=Late life: a new frontier for physiology |url=http://www.escholarship.org/uc/item/4ck3g2pw |journal=Physiological and Biochemical Zoology |volume=78 |issue=6 |pages=869–878 |doi=10.1086/498179 |pmid=16228927|s2cid=31627493 }}

Cell lines

Biologists chose the word "immortal" to designate cells that are not subject to the Hayflick limit, the point at which cells can no longer divide due to DNA damage or shortened telomeres. Prior to Leonard Hayflick's theory, Alexis Carrel hypothesized that all normal somatic cells were immortal.{{Cite journal |last1=Shay, J. W. |last2=Wright, W. E. |name-list-style=amp |year=2000 |title=Hayflick, his limit, and cellular ageing |journal=Nature Reviews Molecular Cell Biology |volume=1 |issue=1 |pages=72–76 |doi=10.1038/35036093 |pmid=11413492|s2cid=6821048 }}

The term "immortalization" was first applied to cancer cells that expressed the telomere-lengthening enzyme telomerase, and thereby avoided apoptosis—i.e. cell death caused by intracellular mechanisms. Among the most commonly used cell lines are HeLa and Jurkat, both of which are immortalized cancer cell lines.{{Cite book |last=Skloot |first=Rebecca |title=The Immortal Life of Henrietta Lacks |title-link=The Immortal Life of Henrietta Lacks |publisher=Crown/Random House |year=2010 |isbn=978-1-4000-5217-2 |location=New York |author-link=Rebecca Skloot}} These cells have been and still are widely used in biological research such as creation of the polio vaccine,{{Cite news |last=Smith |first=Van |url=http://www.citypaper.com/news/story.asp?id=3426 |title=The Life, Death, and Life After Death of Henrietta Lacks, Unwitting Heroine of Modern Medical Science. |date=2002-04-17 |access-date=2010-03-02 |url-status=dead |archive-url=https://web.archive.org/web/20040814160109/http://www.citypaper.com/news/story.asp?id=3426 |archive-date=2004-08-14 |publisher=Baltimore City Paper}} sex hormone steroid research,Bulzomi, Pamela. "The Pro-apoptotic Effect of Quercetin in Cancer Cell Lines Requires ERβ-Dependant Signals." Cellular Physiology (2012): 1891–898. Web. and cell metabolism.{{Citation |last1=Reitzer |first1=Lawrence J. |title=Evidence That Glutamine, Not Sugar, Is the Major Energy Source for Cultured HeLa Cells |journal=The Journal of Biological Chemistry |volume=254 |issue=April 25 |pages=26X9–2676 |year=1978 |pmid=429309 |last2=Wice |first2=Burton M. |last3=Kennel |first3=David}} Embryonic stem cells and germ cells have also been described as immortal.{{cite web |author1=University of Cologne |title=On the immortality of stem cells |url= https://www.sciencedaily.com/releases/2018/03/180307101033.htm |website=ScienceDaily |access-date=17 September 2020 |language=en |date=7 March 2018}}{{cite web |last1=Surani |first1=Azim |title=Germ cells: the route to immortality |url=https://www.cam.ac.uk/research/news/germ-cells-the-route-to-immortality |website=University of Cambridge |access-date=17 September 2020 |language=en |date=1 April 2009}}

Immortal cell lines of cancer cells can be created by induction of oncogenes or loss of tumor suppressor genes. One way to induce immortality is through viral-mediated induction of the large T-antigen,{{Cite journal |last1=Michael R. Rose |last2=Casandra L. Rauser |last3=Laurence D. Mueller |year=1983 |title=Expression of the Large T Protein of Polyoma Virus Promotes the Establishment in Culture of "Normal" Rodent Fibroblast Cell Lines |journal=PNAS |volume=80 |issue=14 |pages=4354–4358 |bibcode=1983PNAS...80.4354R |doi=10.1073/pnas.80.14.4354 |pmc=384036 |pmid=6308618|doi-access=free }} commonly introduced through simian virus 40 (SV-40).{{Cite journal |last1=Irfan Maqsood |first1=M. |last2=Matin |first2=M. M. |last3=Bahrami |first3=A. R. |last4=Ghasroldasht |first4=M. M. |year=2013 |title=Immortality of cell lines: Challenges and advantages of establishment |journal=Cell Biology International |volume=37 |issue=10 |pages=1038–45 |doi=10.1002/cbin.10137 |pmid=23723166|s2cid=14777249 }}

Organisms

According to the Animal Aging and Longevity Database, the list of animals with negligible aging (along with estimated longevity in the wild) includes:[http://genomics.senescence.info/species/nonaging.php Species with Negligible Senescence] {{webarchive|url=https://web.archive.org/web/20150417235935/http://genomics.senescence.info/species/nonaging.php |date=2015-04-17 }}. AnAge: The Animal Ageing and Longevity Database

Blanding's turtle (Emydoidea blandingii) – 77 years
Olm (Proteus anguinus) – 102 years
Eastern box turtle (Terrapene carolina) – 138 years
Red sea urchin (Strongylocentrotus franciscanus) – 200 years
Rougheye rockfish (Sebastes aleutianus) – 205 years
Ocean quahog clam (Arctica islandica) – 507 years
Greenland shark (Somniosus microcephalus) - 250 to 500 years

=Bacteria and some yeast=

Many unicellular organisms age: as time passes, they divide more slowly and ultimately die. Asymmetrically dividing bacteria and yeast also age. However, symmetrically dividing bacteria and yeast can be biologically immortal under ideal growing conditions.Current Biology: Volume 23, Issue 19, 7 October 2013, Pages 1844–1852 "Fission Yeast Does Not Age under Favorable Conditions, but Does So after Stress." Miguel Coelho1, 4, Aygül Dereli1, Anett Haese1, Sebastian Kühn2, Liliana Malinovska1, Morgan E. DeSantis3, James Shorter3, Simon Alberti1, Thilo Gross2, 5, Iva M. Tolić-Nørrelykke1 In these conditions, when a cell splits symmetrically to produce two daughter cells, the process of cell division can restore the cell to a youthful state. However, if the parent asymmetrically buds off a daughter only the daughter is reset to the youthful state—the parent is not restored and will go on to age and die. In a similar manner stem cells and gametes can be regarded as "immortal".{{cn|date=November 2024}}

=Hydra=

File:Hydras (8).JPG

Hydras are a genus of the Cnidaria phylum. All cnidarians can regenerate, allowing them to recover from injury and to reproduce asexually. Hydras are simple, freshwater animals possessing radial symmetry and contain post-mitotic cells (cells that will never divide again) only in the extremities.{{Cite journal|last1=Bellantuono|first1=Anthony J.|last2=Bridge|first2=Diane|last3=Martínez|first3=Daniel E.|date=2015-01-30|title=Hydra as a tractable, long-lived model system for senescence|journal=Invertebrate Reproduction & Development|volume=59|issue=sup1|pages=39–44|doi=10.1080/07924259.2014.938196|issn=0792-4259|pmc=4464093|pmid=26136619|bibcode=2015InvRD..59S..39B }} All hydra cells continually divide.{{cite journal | title=Impact of cycling cells and cell cycle regulation on Hydra regeneration | journal=Developmental Biology | volume=433 | issue=2 | date=2018-01-15 | issn=0012-1606 | doi=10.1016/j.ydbio.2017.11.003 | pages=240–253 | ref={{sfnref | Developmental Biology | 2018}} | doi-access=free | last1=Buzgariu | first1=Wanda | last2=Wenger | first2=Yvan | last3=Tcaciuc | first3=Nina | last4=Catunda-Lemos | first4=Ana-Paula | last5=Galliot | first5=Brigitte | pmid=29291976 }} It has been suggested that hydras do not undergo senescence, and, as such, are biologically immortal. In a four-year study, 3 cohorts of hydra did not show an increase in mortality with age. It is possible that these animals live much longer, considering that they reach maturity in 5 to 10 days.{{Cite journal |last=Martínez |first=Daniel E. |year=1998 |title=Mortality patterns suggest lack of senescence in Hydra |url=http://www.biochem.uci.edu/Steele/PDFs/Hydra_senescence_paper.pdf |url-status=live |journal=Experimental Gerontology |volume=33 |issue=3 |pages=217–225 |citeseerx=10.1.1.500.9508 |doi=10.1016/S0531-5565(97)00113-7 |pmid=9615920 |s2cid=2009972 |archive-url=https://web.archive.org/web/20160426043703/http://www.biochem.uci.edu/steele/PDFs/Hydra_senescence_paper.pdf |archive-date=2016-04-26}} However, this does not explain how hydras are subsequently able to maintain telomere lengths.{{cn|date=November 2024}}

=Jellyfish and comb jellies=

Turritopsis dohrnii and Turritopsis nutricula, is a small ({{convert|5|mm|in|sp=us}}) species of jellyfish that uses transdifferentiation to replenish cells after sexual reproduction. This cycle can repeat indefinitely, potentially rendering it biologically immortal. These organisms originated in the Caribbean Sea, but have now spread around the world.{{cite web |date=January 27, 2009 |title='Immortal' jellyfish swarming across the world |url=https://www.telegraph.co.uk/earth/wildlife/4357829/Immortal-jellyfish-swarming-across-the-world.html |url-status=dead |archive-url=https://web.archive.org/web/20090130115250/http://www.telegraph.co.uk/earth/wildlife/4357829/Immortal-jellyfish-swarming-across-the-world.html |archive-date=January 30, 2009 |access-date=2010-06-16 |publisher=Telegraph Media Group}} Key molecular mechanisms of its rejuvenation appear to involve DNA replication and repair, and stem cell renewal, according to a comparative genomics study.{{cite news |last1=Greenwood |first1=Veronique |title=This Jellyfish Can Live Forever. Its Genes May Tell Us How. |url=https://www.nytimes.com/2022/09/06/science/immortal-jellyfish-gene-protein.html |access-date=22 September 2022 |work=The New York Times |date=6 September 2022}}{{cite journal |last1=Pascual-Torner |first1=Maria |last2=Carrero |first2=Dido |last3=Pérez-Silva |first3=José G. |last4=Álvarez-Puente |first4=Diana |last5=Roiz-Valle |first5=David |last6=Bretones |first6=Gabriel |last7=Rodríguez |first7=David |last8=Maeso |first8=Daniel |last9=Mateo-González |first9=Elena |last10=Español |first10=Yaiza |last11=Mariño |first11=Guillermo |last12=Acuña |first12=José Luis |last13=Quesada |first13=Víctor |last14=López-Otín |first14=Carlos |title=Comparative genomics of mortal and immortal cnidarians unveils novel keys behind rejuvenation |journal=Proceedings of the National Academy of Sciences |date=6 September 2022 |volume=119 |issue=36 |pages=e2118763119 |doi=10.1073/pnas.2118763119 |doi-access=free |pmid=36037356 |pmc=9459311 |bibcode=2022PNAS..11918763P |language=en |issn=0027-8424}}

Similar cases include hydrozoan Laodicea undulata,{{Cite journal |last=De Vito |s2cid=84325535 |display-authors=etal |date=2006 |title=Evidence of reverse development in Leptomedusae (Cnidaria, Hydrozoa): the case of Laodicea undulata (Forbes and Goodsir 1851) |journal=Marine Biology |volume=149 |issue=2 |pages=339–346 |doi=10.1007/s00227-005-0182-3|bibcode=2006MarBi.149..339D }} scyphozoan Aurelia sp.1{{Cite journal |last=He |display-authors=etal |date=2015-12-21 |title=Life Cycle Reversal in Aurelia sp.1 (Cnidaria, Scyphozoa) |journal=PLOS ONE |volume=10 |issue=12 |pages=e0145314 |bibcode=2015PLoSO..1045314H |doi=10.1371/journal.pone.0145314 |pmc=4687044 |pmid=26690755|doi-access=free }} and tentaculata Mnemiopsis leiydi{{Cite journal |last1=Soto-Angel |first1=Joan J. |last2=Burkhardt |first2=Pawel |date=2024-11-05 |title=Reverse development in the ctenophore Mnemiopsis leidyi |journal=Proceedings of the National Academy of Sciences |language=en |volume=121 |issue=45 |pages=e2411499121 |doi=10.1073/pnas.2411499121 |pmid=39471228 |issn=0027-8424|pmc=11551415 |bibcode=2024PNAS..12111499S }}{{Cite web |last=Cockerill |first=Jess |date=2024-11-06 |title=Wild Discovery Reveals That Comb Jellies Can Age in Reverse |url=https://www.sciencealert.com/wild-discovery-reveals-that-comb-jellies-can-age-in-reverse |access-date=2024-11-11 |website=ScienceAlert |language=en-US}}

=Lobsters=

Research suggests that lobsters may not slow down, weaken, or lose fertility with age, and that older lobsters may be more fertile than younger lobsters. This does not however make them immortal in the traditional sense, as they are significantly more likely to die at a shell moult the older they get.

Their longevity may be due to telomerase, an enzyme that repairs long repetitive sections of DNA sequences at the ends of chromosomes, referred to as telomeres. Telomerase is expressed by most vertebrates during embryonic stages but is generally absent from adult stages of life.{{Cite journal |last=Cong YS |date=2002 |title=Human Telomerase and Its Regulation |journal=Microbiology and Molecular Biology Reviews |volume=66 |issue=3 |pages=407–425 |doi=10.1128/MMBR.66.3.407-425.2002 |pmc=120798 |pmid=12208997}} However, unlike vertebrates, lobsters express telomerase as adults through most tissue, which has been suggested to be related to their longevity.{{Cite journal |last1=Wolfram Klapper |last2=Karen Kühne |last3=Kumud K. Singh |last4=Klaus Heidorn |last5=Reza Parwaresch |last6=Guido Krupp |name-list-style=amp |year=1998 |title=Longevity of lobsters is linked to ubiquitous telomerase expression |journal=FEBS Letters |volume=439 |issue=1–2 |pages=143–146 |doi=10.1016/S0014-5793(98)01357-X |pmid=9849895|s2cid=33161779 |doi-access=free |bibcode=1998FEBSL.439..143K }}{{Cite web |url=http://animals.howstuffworks.com/marine-life/400-pound-lobster.htm/printable |title=Is there a 400 pound lobster out there? |last=Jacob Silverman |date=2007-07-05 |publisher=howstuffworks |url-status=live |archive-url=http://archive.wikiwix.com/cache/20110727232039/http://animals.howstuffworks.com/marine-life/400-pound-lobster.htm/printable |archive-date=2011-07-27}}{{Cite book |last=David Foster Wallace |title=Consider the Lobster and Other Essays |title-link=Consider the Lobster |publisher=Little, Brown & Company |year=2005 |isbn=978-0-316-15611-0 |chapter=Consider the Lobster |author-link=David Foster Wallace |chapter-url=http://www.gourmet.com/magazine/2000s/2004/08/consider_the_lobster?currentPage=1 |archive-url=https://web.archive.org/web/20101012023635/http://www.gourmet.com/magazine/2000s/2004/08/consider_the_lobster?currentPage=1 |archive-date=October 12, 2010}} Contrary to popular belief,{{cn|date=May 2025}} lobsters are not immortal. Lobsters grow by moulting, which requires considerable energy, and the larger the shell the more energy is required.{{Cite web |url=http://www.lobsters.org/tlcbio/biology3.html |title=Biotemp |url-status=dead |archive-url=https://web.archive.org/web/20150211101926/http://www.lobsters.org/tlcbio/biology3.html |archive-date=2015-02-11 |access-date=2015-02-10}} Eventually, the lobster will die from exhaustion during a moult. Older lobsters are also known to stop moulting, which means that the shell will eventually become damaged, infected, or fall apart, causing them to die.{{Cite web |url=http://www.smithsonianmag.com/science-nature/dont-listen-to-the-buzz-lobsters-arent-actually-immortal-88450872/?no-ist |title=Don't Listen to the Buzz: Lobsters Aren't Actually Immortal |last=Koren |first=Marina |url-status=live |archive-url=http://archive.wikiwix.com/cache/20150212053821/http://www.smithsonianmag.com/science-nature/dont-listen-to-the-buzz-lobsters-arent-actually-immortal-88450872/?no-ist |archive-date=2015-02-12}} The European lobster has an average life span of 31 years for males and 54 years for females.

=Planarian flatworms=

File:Polycelis felina.jpg

Planarian flatworms have both sexually and asexually reproducing types. Studies on genus Schmidtea mediterranea suggest these planarians appear to regenerate (i.e. heal) indefinitely, and asexual individuals have an "apparently limitless [telomere] regenerative capacity fueled by a population of highly proliferative adult stem cells".{{Cite journal |last1=Thomas C. J. Tan |last2=Ruman Rahman |last3=Farah Jaber-Hijazi |last4=Daniel A. Felix |last5=Chen Chen |last6=Edward J. Louis |last7=Aziz Aboobaker |name-list-style=amp |date=February 2012 |title=Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms |url=http://www.pnas.org/content/early/2012/02/22/1118885109.full.pdf+html |url-status=live |journal=PNAS |volume=109 |issue=9 |pages=4209–4214 |bibcode=2012PNAS..109.4209T |doi=10.1073/pnas.1118885109 |pmc=3306686 |pmid=22371573 |archive-url=https://web.archive.org/web/20120306010425/http://www.pnas.org/content/early/2012/02/22/1118885109.full.pdf+html |archive-date=2012-03-06|doi-access=free }}

For sexually reproducing planaria: "the lifespan of individual planarian can be as long as 3 years, likely due to the ability of neoblasts to constantly replace aging cells". Whereas for asexually reproducing planaria: "individual animals in clonal lines of some planarian species replicating by fission have been maintained for over 15 years".{{Cite web |url=http://www.geochembio.com/biology/organisms/planarian/#dev_stages |title=Schmidtea , model planarian |website=www.geochembio.com |url-status=live |archive-url=https://web.archive.org/web/20101230230657/http://www.geochembio.com/biology/organisms/planarian/#dev_stages |archive-date=2010-12-30}}Archived at [https://ghostarchive.org/varchive/youtube/20211205/RjD1aLm4Thg Ghostarchive]{{cbignore}} and the [https://web.archive.org/web/20181208171657/https://www.youtube.com/watch?v=RjD1aLm4Thg Wayback Machine]{{cbignore}}: {{cite web| url = https://www.youtube.com/watch?v=RjD1aLm4Thg&t=538| title = What Bodies Think About: Bioelectric Computation Outside the Nervous System - NeurIPS 2018 | website=YouTube| date = 5 December 2018 }}{{cbignore}}

References

Bibliography

James L. Halperin. The First Immortal, Del Rey, 1998. {{ISBN|0-345-42092-6}}
Robert Ettinger. The Prospect of Immortality, Ria University Press, 2005. {{ISBN|0-9743472-3-X}}
Dr. R. Michael Perry. Forever For All: Moral Philosophy, Cryonics, and the Scientific Prospects for Immortality, Universal Publishers, 2001. {{ISBN|1-58112-724-3}}
Martinez, D.E. (1998) "Mortality patterns suggest lack of senescence in hydra." Experimental Gerontology 1998 May;33(3):217–225. [http://www.ucihs.uci.edu/biochem/steele/PDFs/Hydra_senescence_paper.pdf Full text.]
{{Cite book |last1=Rose |first1=Michael |title=Does Aging Stop? |last2=Rauser |first2=Casandra L. |last3=Mueller |first3=Laurence D. |date=Spring 2011 |publisher=Oxford University Press }}

Category:Immortality

Category:Senescence