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 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.

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]

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. [13] [14] [15]

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. [16] 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".

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. [17] All hydra cells continually divide. [18] 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. [19] However, this does not explain how hydras are subsequently able to maintain telomere lengths.

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. [20] [21]

Similar cases include hydrozoan Laodicea undulata [22] and scyphozoan Aurelia sp.1. [23]

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 (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. [24] However, unlike vertebrates, lobsters express telomerase as adults through most tissue, which has been suggested to be related to their longevity. [25] [26] [27] 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. [28] 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. [29] The European lobster has an average life span of 31 years for males and 54 years for females.

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". "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... " [30]

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". [31] [32]

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. The word senescence can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence involves an increase in death rates and/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 lack of Hayflick limit. Although it's not the same as immortality as these species can still die from other causes.

Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled biological limit of around 125 years. Several researchers in the area, along with "life extensionists", "immortalists", or "longevists", postulate that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, gene therapy, pharmaceuticals, and organ replacement will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition (agerasia). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.

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">Planarian</span> Flatworms of the Turbellaria class

Planarians (triclads) are free-living flatworms of the class Turbellaria, order Tricladida, which includes hundreds of species, found in freshwater, marine, and terrestrial habitats. Planarians are characterized by a three-branched intestine, including a single anterior and two posterior branches. Their body is populated by adult stem cells called neoblasts, which planarians use for regenerating missing body parts. Many species are able to regenerate any missing organ, which has made planarians a popular model in research of regeneration and stem cell biology. The genome sequences of several species are available, as are tools for molecular biology analysis.

<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. However, this limit does not apply to stem cells.

<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.

Rejuvenation is a medical discipline focused on the practical reversal of the aging process.

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.

Following is a list of topics related to life extension:

<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.

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

<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.

<i>Hydra vulgaris</i> Species of cnidarian

Hydra vulgaris, the fresh-water polyp, is a small freshwater hydroid with length from 10 mm to 30 mm and width about 1 mm.

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.

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