Biological immortality (sometimes referred to bio-indefinite mortality) is a state in which the rate of mortality from senescence 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 or disease.
This definition of immortality has been challenged in the Handbook of the Biology of Aging, 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. As a hypothetical example, there is only a 50% chance of a human surviving another year at age 110 or greater.
The term is also used by biologists to describe cells that are not subject to the Hayflick limit on how many times they can divide.
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.
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. HeLa cells originated from a sample of cervical cancer taken from Henrietta Lacks in 1951. These cells have been and still are widely used in biological research such as creation of the polio vaccine, sex hormone steroid research, and cell metabolism. Normal stem cells and germ cells can also be said to be immortal (when humans refer to the cell line).
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, commonly introduced through simian virus 40 (SV-40).
According to the Animal Aging and Longevity Database, the list of organisms with negligible aging (along with estimated longevity in the wild) includes:
- Rougheye rockfish (Sebastes aleutianus) – 205 years
- Olm (Proteus anguinus) – 102 years
- Painted turtle (Chrysemys picta) – 61 years
- Blanding's turtle (Emydoidea blandingii) – 77 years
- Eastern box turtle (Terrapene carolina) – 138 years
- Red sea urchin (Strongylocentrotus franciscanus) – 200 years
- Ocean quahog clam (Arctica islandica) – 507 years
- Great Basin bristlecone pine (Pinus longaeva) – 4,713 years
- Greenland Shark – 400 years
In 2018, scientists working for Calico, a company owned by Alphabet, published a paper in the journal eLife which presents possible evidence that Heterocephalus glaber (Naked mole rat) do not face increased mortality risk due to aging.
Bacteria and some yeastEdit
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. 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 isn't restored and will go on to age and die. In a similar manner stem cells and gametes can be regarded as "immortal".
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 no post-mitotic cells. All hydra cells continually divide. 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. However, this does not explain how hydras are consequently able to maintain telomere lengths.
Turritopsis dohrnii, or Turritopsis nutricula, is a small (5 millimeters (0.20 in)) species of jellyfish that uses transdifferentiation to replenish cells after sexual reproduction. This cycle can repeat indefinitely, potentially rendering it biologically immortal. This organism originated in the Caribbean sea, but has now spread around the world. Similar cases include hydrozoan Laodicea undulata and scyphozoan Aurelia sp.1.
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 (as detailed below).
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. However, unlike vertebrates, lobsters express telomerase as adults through most tissue, which has been suggested to be related to their longevity. Contrary to popular belief, lobsters are not immortal. Lobsters grow by moulting which requires a lot of energy, and the larger the shell the more energy is required. 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 and they die. The European lobster has an average life span of 31 years for males and 54 years for females.
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". "Both asexual and sexual animals display age-related decline in telomere length; however, asexual animals are able to maintain telomere lengths somatically (i.e. during reproduction by fission or when regeneration is induced by amputation), whereas sexual animals restore telomeres by extension during sexual reproduction or during embryogenesis like other sexual species. Homeostatic telomerase activity observed in both asexual and sexual animals is not sufficient to maintain telomere length, whereas the increased activity in regenerating asexuals is sufficient to renew telomere length... "
Lifespan: 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". They do not live forever.
Attempts to engineer biological immortality in humansEdit
Although the premise that biological aging can be halted or reversed by foreseeable technology remains controversial, research into developing possible therapeutic interventions is underway. Among the principal drivers of international collaboration in such research is the SENS Research Foundation, a non-profit organization that advocates a number of what it claims are plausible research pathways that might lead to engineered negligible senescence in humans.
In 2015, Elizabeth Parrish, CEO of BioViva, treated herself using gene therapy, with the goal of not just halting, but reversing aging. She has since reported feeling more energetic, and no obvious negative side effects have been noticed.
For several decades, researchers have also pursued various forms of suspended animation as a means by which to indefinitely extend mammalian lifespan. Some scientists have voiced support for the feasibility of the cryopreservation of humans, known as cryonics. Cryonics is predicated on the concept that some people considered clinically dead by today's medicolegal standards are not actually dead according to information-theoretic death and can, in principle, be resuscitated given sufficient technological advances. The goal of current cryonics procedures is tissue vitrification, a technique first used to reversibly cryopreserve a viable whole organ in 2005.
Similar proposals involving suspended animation include chemical brain preservation. The non-profit Brain Preservation Foundation offers a cash prize valued at over $100,000 for demonstrations of techniques that would allow for high-fidelity, long-term storage of a mammalian brain.
In 2016, scientists at the Buck Institute for Research on Aging and the Mayo Clinic employed genetic and pharmacological approaches to ablate pro-aging senescent cells, extending healthy lifespan of mice by over 25%. The startup Unity Biotechnology is further developing this strategy in human clinical trials.
In early 2017, Harvard scientists headed by biologist David Sinclair announced they have tested a metabolic precursor that increases NAD+ levels in mice and have successfully reversed the cellular aging process and can protect the DNA from future damage. "The old mouse and young mouse cells are indistinguishable", David was quoted. Human trials are to begin shortly in what the team expect is 6 months at Brigham and Women's Hospital, in Boston.
To achieve the more limited goal of halting the increase in mortality rate with age, a solution must be found to the fact that any intervention to remove senescent cells that creates competition among cells will increase age-related mortality from cancer.
Immortalism and immortality as a movementEdit
In 2012 in Russia, and then in the United States, Israel, and the Netherlands, pro-immortality transhumanist political parties were launched. They aim to provide political support to anti-aging and radical life extension research and technologies and want to ensure the fastest possible—and at the same time, the least disruptive—societal transition to radical life extension, life without aging, and ultimately, immortality. They aim to make it possible to provide access to such technologies to the majority of people alive today.
Future medicine, life extension and "swallowing the doctor"Edit
Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler, one of the founders of nanotechnology, postulated cell repair devices, including ones operating within cells and utilizing as yet hypothetical molecular machines, in his 1986 book Engines of Creation. Raymond Kurzweil, a futurist and transhumanist, stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030. According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him (circa 1959) the idea of a medical use for Feynman's theoretical micromachines (see biological machine). Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would, in theory, be possible to (as Feynman put it) "swallow the doctor". The idea was incorporated into Feynman's 1959 essay There's Plenty of Room at the Bottom.
- Aging brain
- American Academy of Anti-Aging Medicine
- Calico (company)
- DNA damage theory of aging
- Maximum life span
- Methuselah Foundation
- Reliability theory of aging and longevity
- Rejuvenation (aging)
- Strategies for Engineered Negligible Senescence (SENS)
- Telomerase in cancer cell
- Timeline of senescence research
- Masoro, E.J. (2006). Austad, S.N., ed. Handbook of the Biology of Aging (Sixth ed.). San Diego, CA: Academic Press. ISBN 978-0-12-088387-5.
- Michael R. Rose; Casandra L. Rauser; Laurence D. Mueller (Nov–Dec 2005). "Late life: a new frontier for physiology". Physiological and Biochemical Zoology. 78 (6): 869–878. doi:10.1086/498179. PMID 16228927.
- Shay, J. W. & Wright, W. E. (2000). "Hayflick, his limit, and cellular ageing" (PDF). Nature Reviews Molecular Cell Biology. 1 (1): 72–76. doi:10.1038/35036093. PMID 11413492.[permanent dead link]
- Skloot, Rebecca (2010). The Immortal Life of Henrietta Lacks. New York: Crown/Random House. ISBN 978-1-4000-5217-2.
- Smith, Van (2002-04-17). "The Life, Death, and Life After Death of Henrietta Lacks, Unwitting Heroine of Modern Medical Science". Baltimore City Paper. Archived from the original on 2004-08-14. Retrieved 2010-03-02.
- Bulzomi, Pamela. "The Pro-apoptotic Effect of Quercetin in Cancer Cell Lines Requires ERβ-Dependant Signals." Cellular Physiology (2012): 1891-898. Web.
- Reitzer, Lawrence J.; Wice, Burton M.; Kennel, David (1978), "Evidence That Glutamine, Not Sugar, Is the Major Energy Source for Cultured HeLa Cells", The Journal of Biological Chemistry, 254 (April 25): 26X9–2676, doi:10.1073/pnas.1117500108, PMC 3248543, PMID 22106309, archived from the original on 2012-03-06, retrieved 2013-04-03
- Michael R. Rose; Casandra L. Rauser; Laurence D. Mueller (1983). "Expression of the Large T Protein of Polyoma Virus Promotes the Establishment in Culture of "Normal" Rodent Fibroblast Cell Lines". PNAS. 80 (14): 4354–4358. doi:10.1073/pnas.80.14.4354. PMC 384036. PMID 6308618.
- Irfan Maqsood, M.; Matin, M. M.; Bahrami, A. R.; Ghasroldasht, M. M. (2013). "Immortality of cell lines: Challenges and advantages of establishment". Cell Biology International. 37 (10): 1038–45. doi:10.1002/cbin.10137. PMID 23723166.
- Species with Negligible Senescence Archived 2015-04-17 at the Wayback Machine. AnAge: The Animal Ageing and Longevity Database
- Pennisi, Elizabeth (11 August 2016). "Greenland Shark May Live 400 Years, Smashing Longevity Record". Science Magazine. Archived from the original on 12 August 2016.
- "Calico Scientists Publish Paper in eLife Demonstrating that the Naked Mole Rat's Risk of Death Does Not Increase With Age". Calico. 25 January 2018. Archived from the original on 27 January 2018. Retrieved 27 January 2018.
- "Naked mole rats defy the biological law of aging". Science Magazine - AAAS. 26 January 2018. Archived from the original on 26 January 2018. Retrieved 27 January 2018.
- Ruby, Graham; Smith, Megan; Buffenstein, Rochelle (25 January 2018). "Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age". eLife. 7. doi:10.7554/eLife.31157. PMID 29364116. Archived from the original on 26 January 2018. Retrieved 27 January 2018.
- 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
- Martínez, Daniel E. (1998). "Mortality patterns suggest lack of senescence in Hydra" (PDF). Experimental Gerontology. 33 (3): 217–225. CiteSeerX 10.1.1.500.9508. doi:10.1016/S0531-5565(97)00113-7. PMID 9615920. Archived (PDF) from the original on 2016-04-26.
- De Vito; et al. (2006). "Evidence of reverse development in Leptomedusae (Cnidaria, Hydrozoa): the case of Laodicea undulata (Forbes and Goodsir 1851)". Marine Biology. 149 (2): 339–346. doi:10.1007/s00227-005-0182-3.
- He; et al. (2015-12-21). "Life Cycle Reversal in Aurelia sp.1 (Cnidaria, Scyphozoa)". PLOS ONE. 10 (12): e0145314. doi:10.1371/journal.pone.0145314. PMC 4687044. PMID 26690755.
- Cong YS (2002). "Human Telomerase and Its Regulation". Microbiology and Molecular Biology Reviews. 66 (3): 407–425. doi:10.1128/MMBR.66.3.407-425.2002. PMC 120798. PMID 12208997.
- Wolfram Klapper; Karen Kühne; Kumud K. Singh; Klaus Heidorn; Reza Parwaresch & Guido Krupp (1998). "Longevity of lobsters is linked to ubiquitous telomerase expression". FEBS Letters. 439 (1–2): 143–146. doi:10.1016/S0014-5793(98)01357-X.
- Jacob Silverman (2007-07-05). "Is there a 400 pound lobster out there?". howstuffworks. Archived from the original on 2011-07-27.
- David Foster Wallace (2005). "Consider the Lobster". Consider the Lobster and Other Essays. Little, Brown & Company. ISBN 978-0-316-15611-0. Archived from the original on
- "Archived copy". Archived from the original on 2015-02-11. Retrieved 2015-02-10.CS1 maint: Archived copy as title (link)
- Koren, Marina. "Don't Listen to the Buzz: Lobsters Aren't Actually Immortal". Archived from the original on 2015-02-12.
- Thomas C. J. Tan; Ruman Rahman; Farah Jaber-Hijazi; Daniel A. Felix; Chen Chen; Edward J. Louis & Aziz Aboobaker (February 2012). "Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms". PNAS. 109 (9): 4209–4214. doi:10.1073/pnas.1118885109. PMC 3306686. PMID 22371573. Archived from the original on 2012-03-06.
- "Schmidtea , model planarian". www.geochembio.com. Archived from the original on 2010-12-30.
- Holliday, Robin (April 2009). "The extreme arrogance of anti-aging medicine". Biogerontology. 10 (2): 223–228. doi:10.1007/s10522-008-9170-6. PMID 18726707.
- "Rejuvenation Research". Mary Ann Liebert, Inc.
- "A Reimagined Research Strategy for Aging". SENS Research Foundation. 2012-11-19. Archived from the original on 27 May 2013. Retrieved 1 June 2013.
- Aguiar, Sebastian. "The Renaissance of Rejuvenation Biotechnology". Longevity Reporter. Archived from the original on 2018-03-05. Retrieved 2018-03-04.
- "A Tale of Do-It-Yourself Gene Therapy".
- Hartman, Brady (February 12, 2018). "BioViva's Liz Parrish reports promising progress on human gene therapy". LongevityFacts.
- Smith, Audrey U (1957). "Problems in the Resuscitation of Mammals from Body Temperatures Below 0 degrees C". Proceedings of the Royal Society of London. Series B, Biological Sciences. 147 (929): 533–44. doi:10.1098/rspb.1957.0077. JSTOR 83173.
- "Scientists Open Letter on Cryonics". 2012-01-15. Archived from the original on 2016-08-26. Retrieved 2013-03-19.
- "Alcor: Cryonics Myths". Archived from the original on 2 June 2013. Retrieved 1 June 2013.
- "Plenary Session: Fundamentals of Biopreservation". CRYO 2005 Scientific Program. Society for Cryobiology. July 24, 2005. Archived from the original on 2006-08-30. Retrieved 2006-11-08.
- Fahy GM, Wowk B, Pagotan R, Chang A, Phan J, Thomson B, Phan L (2009). "Physical and biological aspects of renal vitrification". Organogenesis. 5 (3): 167–175. doi:10.4161/org.5.3.9974. PMC 2781097. PMID 20046680.
- "Brain Preservation Foundation: Technology Prize". Archived from the original on 17 May 2013. Retrieved 1 June 2013.
- "25% Median Life Extension in Mice via Senescent Cell Clearance, Unity Biotechnology Founded to Develop Therapies". Fight Aging!. 2016-02-03. Archived from the original on 2018-03-12. Retrieved 2018-03-04.
- "Harvard scientists pinpoint critical step in DNA repair, cellular aging". Harvard Gazette. 2017-03-23. Retrieved 2017-04-22.
- Nelson, Paul; Masel, Joanna (5 December 2017). "Intercellular competition and the inevitability of multicellular aging". Proceedings of the National Academy of Sciences. 114 (49): 12982–12987. doi:10.1073/pnas.1618854114. PMC 5724245. PMID 29087299.
- "The Longevity Party - Who Needs it? Who Wants it?". Archived from the original on 29 April 2014. Retrieved 4 April 2014.
- "A Single-Issue Political Party for Longevity Science". Fight Aging!. July 27, 2012. Archived from the original on January 16, 2013. Retrieved January 31, 2013.
- Kurzweil, Ray (2005). The Singularity Is Near. New York City: Viking Press. ISBN 978-0-670-03384-3. OCLC 57201348.[page needed]
- Richard P. Feynman (December 1959). "There's Plenty of Room at the Bottom". Archived from the original on 11 February 2010. Retrieved 14 April 2016.
- 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. Full text.
- Rose, Michael; Rauser, Casandra L.; Mueller, Laurence D. (Spring 2011). Does Aging Stop?. Oxford University Press.
|Look up biological immortality in Wiktionary, the free dictionary.|
- Biological Immortality Slide show by Michael R. Rose
- Cellular Senescence and Apoptosis in Aging
- Cellular Senescence Information Center
- Geron Announces Launch of Telomerase-Immortalized Cell Line Geron Corporation
- Late Life: A New Frontier for Physiology study indicates biological immortality in humans late in life
- No Limit to Lifespan if We're Machines (pdf) – Betterhumans, August 26, 2004
- Peter Pan girl's DNA may hold secret to immortality