Biological immortality

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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.

Contents

This definition of immortality has been challenged in the Handbook of the Biology of Aging, [1] 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. [2]

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. [ citation needed ]

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. [3]

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. [4] These cells have been and still are widely used in biological research such as creation of the polio vaccine, [5] sex hormone steroid research, [6] and cell metabolism. [7] Embryonic stem cells and germ cells have also been described as immortal. [8] [9]

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, [10] commonly introduced through simian virus 40 (SV-40). [11]

Organisms

According to the Animal Aging and Longevity Database, the list of animals with negligible aging (along with estimated longevity in the wild) includes: [12]

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. [13] 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".[ citation needed ]

Hydra

Hydra Hydras (8).JPG
Hydra

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. [14] All hydra cells continually divide. [15] 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. [16] However, this does not explain how hydras are subsequently able to maintain telomere lengths.[ citation needed ]

Jellyfish

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.[ citation needed ] Key molecular mechanisms of its rejuvenation appear to involve DNA replication and repair, and stem cell renewal, according to a comparative genomics study. [17] [18]

Similar cases include hydrozoan Laodicea undulata [19] , scyphozoan Aurelia sp.1 [20] and tentaculata Mnemiopsis Leiydi [21] [22]

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[ citation needed ] .

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. [23] However, unlike vertebrates, lobsters express telomerase as adults through most tissue, which has been suggested to be related to their longevity. [24] [25] [26] Contrary to popular belief, lobsters are not immortal. Lobsters grow by moulting, which requires considerable energy, and the larger the shell the more energy is required. [27] 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. [28] The European lobster has an average life span of 31 years for males and 54 years for females.[ citation needed ]

Planarian flatworms

Polycelis felina, a freshwater planarian Polycelis felina.jpg
Polycelis felina, a freshwater planarian

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". [29]

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". [30] [31]

See also

Related Research Articles

<i>Hydra</i> (genus) Genus of cnidarians

Hydra is a genus of small freshwater hydrozoans of the phylum Cnidaria. They are native to the temperate and tropical regions. The genus was named by Linnaeus in 1758 after the Hydra, which was the many-headed beast of myth defeated by Heracles, as when the animal has a part severed, it will regenerate much like the mythical hydra's heads. Biologists are especially interested in Hydra because of their regenerative ability; they do not appear to die of old age, or to age at all.

<span class="mw-page-title-main">Telomere</span> Region of repetitive nucleotide sequences on chromosomes

A telomere is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most, if not all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break.

Senescence or biological aging is the gradual deterioration of functional characteristics in living organisms. Whole organism senescence involves an increase in death rates or a decrease in fecundity with increasing age, at least in the later part of an organism's life cycle. However, the resulting effects of senescence can be delayed. The 1934 discovery that calorie restriction can extend lifespans by 50% in rats, the existence of species having negligible senescence, and the existence of potentially immortal organisms such as members of the genus Hydra have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.

<span class="mw-page-title-main">Immortality</span> Concept of eternal life

Immortality is the concept of eternal life. Some species possess 'biological immortality' due to an apparent lack of the Hayflick limit.

Maximum life span is a measure of the maximum amount of time one or more members of a population have been observed to survive between birth and death. The term can also denote an estimate of the maximum amount of time that a member of a given species could survive between birth and death, provided circumstances that are optimal to that member's longevity.

<span class="mw-page-title-main">Telomerase</span> Telomere-restoring protein active in the most rapidly dividing cells

Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. The fruit fly Drosophila melanogaster lacks telomerase, but instead uses retrotransposons to maintain telomeres.

<span class="mw-page-title-main">Hayflick limit</span> Limit to divisions of a normal human cell

The Hayflick limit, or Hayflick phenomenon, is the number of times a normal somatic, differentiated human cell population will divide before cell division stops.

<span class="mw-page-title-main">Michael D. West</span> American biogerontologist

Michael D. West is an American biogerontologist, and a pioneer in stem cells, cellular aging and telomerase. He is the founder and CEO of AgeX Therapeutics, a startup focused on the field of experimental gerontology.

Enquiry into the evolution of ageing, or aging, aims to explain why a detrimental process such as ageing would evolve, and why there is so much variability in the lifespans of organisms. The classical theories of evolution suggest that environmental factors, such as predation, accidents, disease, and/or starvation, ensure that most organisms living in natural settings will not live until old age, and so there will be very little pressure to conserve genetic changes that increase longevity. Natural selection will instead strongly favor genes which ensure early maturation and rapid reproduction, and the selection for genetic traits which promote molecular and cellular self-maintenance will decline with age for most organisms.

<span class="mw-page-title-main">Eternal youth</span> Physical immortality free of ageing

Eternal youth is the concept of human physical immortality free of ageing. The youth referred to is usually meant to be in contrast to the depredations of aging, rather than a specific age of the human lifespan. Eternal youth is common in mythology, and is a popular theme in fiction.

<span class="mw-page-title-main">Carol W. Greider</span> American molecular biologist and Nobel laureate

Carolyn Widney Greider is an American molecular biologist and Nobel laureate. She is a Distinguished Professor of Molecular, Cell, and Developmental Biology at the University of California, Santa Cruz.

The following outline is provided as an overview of and topical guide to life extension:

<span class="mw-page-title-main">Telomerase reverse transcriptase</span> Catalytic subunit of the enzyme telomerase

Telomerase reverse transcriptase is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex.

<span class="mw-page-title-main">Cellular senescence</span> Phenomenon characterized by the cessation of cell division

Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process is known as "replicative senescence", or the Hayflick limit. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things.

<span class="mw-page-title-main">Clone (cell biology)</span> Group of identical cells that share a common ancestry

A clone is a group of identical cells that share a common ancestry, meaning they are derived from the same cell.

<span class="mw-page-title-main">Negligible senescence</span> Organisms that do not exhibit evidence of biological aging

Negligible senescence is a term coined by biogerontologist Caleb Finch to denote organisms that do not exhibit evidence of biological aging (senescence), such as measurable reductions in their reproductive capability, measurable functional decline, or rising death rates with age. There are many species where scientists have seen no increase in mortality after maturity. This may mean that the lifespan of the organism is so long that researchers' subjects have not yet lived up to the time when a measure of the species' longevity can be made. Turtles, for example, were once thought to lack senescence, but more extensive observations have found evidence of decreasing fitness with age.

Shelterin is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double-stranded 5'-TTAGGG-3' (G-strand) sequences along with the 3'-AATCCC-5' (C-strand) complement, ending with a 50-400 nucleotide 3' (G-strand) overhang. Much of the final double-stranded portion of the telomere forms a T-loop (Telomere-loop) that is invaded by the 3' (G-strand) overhang to form a small D-loop (Displacement-loop).

<span class="mw-page-title-main">WI-38</span> Human cell line composed of fibroblasts

WI-38 is a diploid human cell line composed of fibroblasts derived from lung tissue of a 3-month-gestation female fetus. The fetus came from the elective abortion of a Swedish woman in 1963. The cell line was isolated by Leonard Hayflick the same year, and has been used extensively in scientific research, with applications ranging from developing important theories in molecular biology and aging to the production of most human virus vaccines. The uses of this cell line in human virus vaccine production is estimated to have saved the lives of millions of people.

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. The hallmarks of aging are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity, impaired function and, eventually, death. They were first listed in a landmark paper in 2013 to conceptualize the essence of biological aging and its underlying mechanisms.

<span class="mw-page-title-main">Relationship between telomeres and longevity</span>

The relationship between telomeres and longevity and changing the length of telomeres is one of the new fields of research on increasing human lifespan and even human immortality. Telomeres are sequences at the ends of chromosomes that shorten with each cell division and determine the lifespan of cells. The telomere was first discovered by biologist Hermann Joseph Muller in the early 20th century. However, experiments by Elizabeth Blackburn, Carol Greider, and Jack Szostak in the 1980s led to the successful discovery of telomerase and a better understanding of telomeres.

References

  1. ↑ 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.
  2. ↑ 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. S2CID   31627493.
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  4. ↑ Skloot, Rebecca (2010). The Immortal Life of Henrietta Lacks. New York: Crown/Random House. ISBN   978-1-4000-5217-2.
  5. ↑ 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.
  6. ↑ Bulzomi, Pamela. "The Pro-apoptotic Effect of Quercetin in Cancer Cell Lines Requires ERβ-Dependant Signals." Cellular Physiology (2012): 1891-898. Web.
  7. ↑ 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, PMID   429309
  8. ↑ University of Cologne (7 March 2018). "On the immortality of stem cells". ScienceDaily. Retrieved 17 September 2020.
  9. ↑ Surani, Azim (1 April 2009). "Germ cells: the route to immortality". University of Cambridge. Retrieved 17 September 2020.
  10. ↑ 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. Bibcode:1983PNAS...80.4354R. doi: 10.1073/pnas.80.14.4354 . PMC   384036 . PMID   6308618.
  11. ↑ 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. S2CID   14777249.
  12. ↑ Species with Negligible Senescence Archived 2015-04-17 at the Wayback Machine . AnAge: The Animal Ageing and Longevity Database
  13. ↑ 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
  14. ↑ Bellantuono, Anthony J.; Bridge, Diane; Martínez, Daniel E. (2015-01-30). "Hydra as a tractable, long-lived model system for senescence". Invertebrate Reproduction & Development. 59 (sup1): 39–44. Bibcode:2015InvRD..59S..39B. doi:10.1080/07924259.2014.938196. ISSN   0792-4259. PMC   4464093 . PMID   26136619.
  15. ↑ Buzgariu, Wanda; Wenger, Yvan; Tcaciuc, Nina; Catunda-Lemos, Ana-Paula; Galliot, Brigitte (2018-01-15). "Impact of cycling cells and cell cycle regulation on Hydra regeneration". Developmental Biology. 433 (2): 240–253. doi: 10.1016/j.ydbio.2017.11.003 . ISSN   0012-1606. PMID   29291976.
  16. ↑ 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. S2CID   2009972. Archived (PDF) from the original on 2016-04-26.
  17. ↑ Greenwood, Veronique (6 September 2022). "This Jellyfish Can Live Forever. Its Genes May Tell Us How". The New York Times. Retrieved 22 September 2022.
  18. ↑ Pascual-Torner, Maria; Carrero, Dido; Pérez-Silva, José G.; Álvarez-Puente, Diana; Roiz-Valle, David; Bretones, Gabriel; Rodríguez, David; Maeso, Daniel; Mateo-González, Elena; Español, Yaiza; Mariño, Guillermo; Acuña, José Luis; Quesada, Víctor; López-Otín, Carlos (6 September 2022). "Comparative genomics of mortal and immortal cnidarians unveils novel keys behind rejuvenation". Proceedings of the National Academy of Sciences. 119 (36): e2118763119. Bibcode:2022PNAS..11918763P. doi: 10.1073/pnas.2118763119 . ISSN   0027-8424. PMC   9459311 . PMID   36037356.
  19. ↑ 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. Bibcode:2006MarBi.149..339D. doi:10.1007/s00227-005-0182-3. S2CID   84325535.
  20. ↑ He; et al. (2015-12-21). "Life Cycle Reversal in Aurelia sp.1 (Cnidaria, Scyphozoa)". PLOS ONE. 10 (12): e0145314. Bibcode:2015PLoSO..1045314H. doi: 10.1371/journal.pone.0145314 . PMC   4687044 . PMID   26690755.
  21. ↑ Soto-Angel, Joan J.; Burkhardt, Pawel (2024-11-05). "Reverse development in the ctenophore Mnemiopsis leidyi". Proceedings of the National Academy of Sciences. 121 (45). doi:10.1073/pnas.2411499121. ISSN   0027-8424.
  22. ↑ Cockerill, Jess (2024-11-06). "Wild Discovery Reveals That Comb Jellies Can Age in Reverse". ScienceAlert. Retrieved 2024-11-11.
  23. ↑ 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.
  24. ↑ 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. Bibcode:1998FEBSL.439..143K. doi: 10.1016/S0014-5793(98)01357-X . PMID   9849895. S2CID   33161779.
  25. ↑ Jacob Silverman (2007-07-05). "Is there a 400 pound lobster out there?". howstuffworks. Archived from the original on 2011-07-27.
  26. ↑ 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 October 12, 2010.
  27. ↑ "Biotemp". Archived from the original on 2015-02-11. Retrieved 2015-02-10.
  28. ↑ Koren, Marina. "Don't Listen to the Buzz: Lobsters Aren't Actually Immortal". Archived from the original on 2015-02-12.
  29. ↑ 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. Bibcode:2012PNAS..109.4209T. doi: 10.1073/pnas.1118885109 . PMC   3306686 . PMID   22371573. Archived from the original on 2012-03-06.
  30. ↑ "Schmidtea , model planarian". www.geochembio.com. Archived from the original on 2010-12-30.
  31. ↑ Archived at Ghostarchive and the Wayback Machine : "What Bodies Think About: Bioelectric Computation Outside the Nervous System - NeurIPS 2018". YouTube . 5 December 2018.

Bibliography

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