Phenoptosis (pheno - showing or demonstrating, ptosis - programmed death), designated by V.P. Skulachev in 1999, signifies the phenomenon of programmed death of an organism, i.e. that an organism's genes include features that under certain circumstances will cause the organism to rapidly degenerate and die off. Recently this has been referred to as “fast phenoptosis” as aging is being explored as “slow phenoptosis.”[1] Phenoptosis is a common feature of living species, whose ramifications for humans is still being explored.

Evolutionary significance

Inside of our bodies, worn-out, ineffective cells are dismantled and recycled for the greater good of the whole organism. This is a process called apoptosis. It is believed that phenoptosis is an evolutionary mechanism that culls out the damaged, aged, infectious, or those in direct competition with their own offspring [2] for the good of the species. The elimination of parts detrimental to the organism or individuals detrimental to the species has been deemed “The samurai law of biology”- it is better to die than to be wrong.[3] ‘’’Stress-induced, acute, or fast phenoptosis’’’ is the rapid deterioration of an organism induced by a life event such as breeding. Elimination of the parent provides space for fitter offspring. As a species this has been advantageous particularly to species that die immediately after spawning.[2] ‘’’Age-induced, soft, or slow phenoptosis’’’ is the slow deterioration and death of an organism due to accumulated stresses over long periods of time. In short, it has been proposed that aging, heart disease, cancer, and other age related ailments are means of phenoptosis. “Death caused by aging clears the population of ancestors and frees space for progeny carrying new useful traits.” [3] It has also been proposed that age provides a selective advantage to brains over brawn.[4] An example made by V. P. Skulachev provides that of two hares, one faster and one smarter, the faster hare may have a selective advantage in youth but as aging occurs and muscles deteriorate it is the smarter hare that now has the selective advantage.

Examples in nature

E. coli – programmed death is initiated by infection by phage. This prevents further spread of phage to the remaining population.[5]

Saccharomyces cerevisiae – Under stress the yeast mitochondria produce reactive oxygen species ROS, leading to loss of membrane potential within the mitochondria and death of the cell.[6]

Amoeba Dictyostelium – Under stress amoeba form multicellular fruiting bodies. The better nourished cells differentiate into spores. The less healthy cells differentiate into the stalks of the fruiting body. After maturation of the spores, the stalk cells undergo phenoptosis.[7]

Nematode Caenorhabditis elegans – Under normal conditions Caenorhabditis elegans display a normal aging life cycle. However, if there is increased stress after breeding they undergo phenoptosis, like in yeast, induced by the mitochondria.[8]

Mayfly – Adult mayflies have no functional mouth and die from malnutrition.[2]

Praying mantis – The male praying mantis ejaculates only after being decapitated by the female.[9]

Mite Adactylidium – The initial food source of Adactylidium mitelarvae is the body tissues of their mother resulting in her death.[6]

Squid – Some male squid die immediately after mating. This provides an abundant food source for those predators that would prey on the eggs.[10]

marsupial mice – Males die 2 weeks after reproducing from an overabundance of their own pheromones.[6]

Salmon – Die soon after spawning.[11]

Septic shock – Severe infection by pathogens often results in death by sepsis. Sepsis, however, is not a result of toxins activated by the pathogen, rather it is directed by the organism itself. Similar to phenoptosis of E. Coli, this has been suggested to be a means to separate dangerously infected individuals from healthy ones.[5]

Examples in humans

Vascular disease, menopause, cancer, and osteoarthritis[12] have been suggested to be means of human phenoptosis. Phenoptosis has recently been heavily studied in the hopes of increasing human longevity. By understanding the mechanisms of slow phenoptosis we may be able to halt or even reverse the processes that cause our aging and eventual deaths.

Proposed mechanisms

Mitochondrial ROS – The production of ROS by the mitochondria. This causes oxidative damage to the inner compartment of the mitochondria and destruction of the mitochondria.[5]

Clk1 gene – the gene thought to be responsible to aging due to mitochondrial ROS.[13]

EF2 kinase – Blocks phosphorylation of elongation factor 2 thus blocking protein synthesis.[14]

Glucocorticoid regulation - A common route for phenoptosis is breakdown of glucocorticoid regulation and inhibition, leading to massive excess of these corticosteroids in the body.[3]

Other examples

Robert Sapolsky discusses phenoptosis in his book Why Zebras Don't Get Ulcers, 3rd Ed., p. 245-247. He states that:

"If you catch salmon right after they spawn... you find they have huge adrenal glands, peptic ulcers, and kidney lesions, their immune systems have collapsed... [and they] have stupendously high glucocorticoid concentrations in their bloodstreams. When salmon spawn, regulation of their glucocortocoid secretion breaks down... But is the glucocorticoid excess really responsible for their death? Yup. Take a salmon right after spawning, remove its adrenals, and it will live for a year afterward.
"The bizarre thing is that this sequence... not only occurs in five species of salmon, but also among a dozen species of Australian marsupial mice... Pacific salmon and marsupial mice are not close relatives. At least twice in evolutionary history, completely independently, two very different sets of species have come up with the identical trick: if you want to degenerate very fast, secrete a ton of glucocorticoids."


  1. Skulachev, V.P. (November 1997). "Organism's Aging is a Special Biological Function Rather than a Result of Breakdown of a Complex Biological System: Biochemical Support of Weismann's Hypothesis". Biokhimiya. 62 (12): 1191–1195. PMID 9467841.
  2. 1 2 3 Weismann, A (1889). Essays upon Heredity and Kindred Bio_. Oxford: Clarendon Press. p. 23. ISBN 1172574987.
  3. 1 2 3 Skulachev, VP (Apr 2002). "Programmed death phenomena: from organelle to organism.". Ann N Y Acad Sci. 959: 214–237. doi:10.1111/j.1749-6632.2002.tb02095.x. PMID 11976198.
  4. Skulachev, VP (November 2011). "Aging as a particular case of phenoptosis, the programmed death of an organism (A response to Kirkwood and Melov "On the programmed/non-programmed nature of ageing within the life history")". Aging. 3 (11): 1120–1123. PMC 3249457Freely accessible. PMID 22146104.
  5. 1 2 3 Skulachev, VP (December 1999). "Phenoptosis: programmed death of an organism.". Biokhimiya. 64 (12): 1418–1426. PMID 10648966.
  6. 1 2 3 Severin, FF; Skulachev, VP (2011). "Programmed Cell Death as a Target to Interrupt the Aging Program". Advances in Gerontology. 1 (1): 16–27. doi:10.1134/S2079057011010139.
  7. Thompson, CR; Kay, RR (November 2000). "Cell-FateChoice in Dictyostelium: Intrinsic Biases Modulate Sensitivity to DIF Signaling". Developmental Biology. 277 (1): 56–64. doi:10.1006/dbio.2000.9877.
  8. Pestov, NB; Shakhparonov, M.; Korneenko, T. (Sep–Oct 2011). "Matricide in Caenorhabditis elegans as an example of programmed death of an animal organism: The role of mitochondrial oxidative stress". Russian Journal of Bioorganic Chemistry. 37 (5): 705–710. doi:10.1134/S106816201105013X. PMID 22332368.
  9. Dawkins, R (1976). The Selfish Gene. Oxford: Oxford Univ.Press. ISBN 0192860925.
  10. Nesis, K (1997). "A Cruel Love of Squids". The Russian Science:To Withstand and Resurrect: 358–365.
  11. Kirkwood, TB; Cremer T (1982). "Cytogerontology since 1881: a reappraisal of August Weismann and a review of modern progress.". Hum Genet. 60 (2): 101–121. doi:10.1007/BF00569695. PMID 7042533.
  12. Yun, A; Lee, P.; Doux, J. (2006). "Osteoarthritis: An example of phenoptosis through autonomic dysfunction?". Medical Hypotheses. 67 (5): 1079–1085. doi:10.1016/j.mehy.2006.02.026.
  13. Liu, X; Jiang, N.; Bigras, E.; Shoubridge, E.; Hekimi, S. (15 Oct 2005). "Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice.". Genes Dev. 19 (20): 2424–34. doi:10.1101/gad.1352905. PMC 1257397Freely accessible. PMID 16195414.
  14. Holley, CL; Michael R. Olson; Daniel A. Colón-Ramos; Sally Kornbluth (June 2002). "Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition". Nat Cell Biol. 4 (6): 439–444. doi:10.1038/ncb798.

See also

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