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What are the molecular and cellular characteristics of immortal organisms? Can we mimic them?

Image credit: Muzina Shanghai

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Shubhankar Kulkarni
Shubhankar Kulkarni Oct 16, 2020
11
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Can we learn from exceptionally long-living plants?

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Subash Chapagain
Subash Chapagain Oct 17, 2020

[1]Flanary, B. E., & Kletetschka, G. (2005). Analysis of telomere length and telomerase activity in tree species of various life-spans, and with age in the bristlecone pine Pinus longaeva. Biogerontology, 6(2), 101–111. https://doi.org/10.1007/s10522-005-3484-4

[2]Song, J., Logeswaran, D., Castillo-González, C., Li, Y., Bose, S., Aklilu, B. B., Ma, Z., Polkhovskiy, A., Chen, J. J.-L., & Shippen, D. E. (2019). The conserved structure of plant telomerase RNA provides the missing link for an evolutionary pathway from ciliates to humans. Proceedings of the National Academy of Sciences, 116(49), 24542–24550. https://doi.org/10.1073/pnas.1915312116

[3]J. W. Shay, W. E. Wright, Telomeres and telomerase: Three decades of progress. Nat. Rev. Genet. 20, 299–309 (2019)

[4]J. D. Podlevsky, J. J. Chen, Evolutionary perspectives of telomerase RNA structure and function. RNA Biol. 13, 720–732 (2016).

[5]Shemesh, H., Boaz, B. E., Millar, C. I., & Bruns, T. D. (2019). Symbiotic interactions above treeline of long‐lived pines: Mycorrhizal advantage of limber pine ( Pinus flexilis ) over Great Basin bristlecone pine ( Pinus longaeva ) at the seedling stage. Journal of Ecology, 108(3), 908–916. https://doi.org/10.1111/1365-2745.13312

Not immortal, but very very old shark

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J
Juran Oct 27, 2020

[1]https://link.springer.com/article/10.1007/s00401-020-02237-4?fbclid=IwAR13IuRKKXPCW17Aq3mAaqPv_GXp0owqr8TlejSdAys58-GFqJwJzpDjUOk

Elephants are more resistant to cancer compared to humans

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Shubhankar Kulkarni
Shubhankar Kulkarni Nov 04, 2020

[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858328/#:~:text=Compared%20with%20other%20mammalian%20species,apoptotic%20response%20following%20DNA%20damage.

The curious case of Turritopsis dohrnii

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Povilas S
Povilas S Nov 24, 2020

Hydra stem cells are immune to changes in the nuclear envelope architecture

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Shubhankar Kulkarni
Shubhankar Kulkarni Oct 16, 2020

[1]Lattanzi G, Ortolani M, Columbaro M, Prencipe S, Mattioli E, Lanzarini C, et al. Lamins are rapamycin targets that impact human longevity: a study in centenarians. J Cell Sci [Internet]. 2014 Jan 1;127(1):147–57. Available from: http://jcs.biologists.org/cgi/doi/10.1242/jcs.133983

[2]Klimovich A, Rehm A, Wittlieb J, Herbst E-M, Benavente R, Bosch TCG. Non-senescent Hydra tolerates severe disturbances in the nuclear lamina. Aging (Albany NY) [Internet]. 2018 May 10;10(5):951–72. Available from: https://www.aging-us.com/lookup/doi/10.18632/aging.101440

The senescent cells in a naked mole rat are metabolically less active and cannot overcome oxidative stress

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Shubhankar Kulkarni
Shubhankar Kulkarni Oct 16, 2020

[1]Zhao Y, Tyshkovskiy A, Muñoz-Espín D, Tian X, Serrano M, de Magalhaes JP, et al. Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence. Proc Natl Acad Sci [Internet]. 2018 Feb 20;115(8):1801–6. Available from: http://www.pnas.org/lookup/doi/10.1073/pnas.1721160115

[2]Kawamura Y, Oka K, Takamori M, Sugiura Y, Oiwa Y, Fujioka S, et al. Senescent cell death as an aging resistance mechanism in naked mole-rat. bioRxiv [Internet]. 2020; Available from: https://www.biorxiv.org/content/10.1101/2020.07.02.155903v1

Can we learn from Tardigrades?

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Antonio Carusillo
Antonio Carusillo Oct 17, 2020

[1]Jönsson KI, Holm I, Tassidis H. Cell Biology of the Tardigrades: Current Knowledge and Perspectives. Results Probl Cell Differ. 2019;68:231-249. doi: 10.1007/978-3-030-23459-1_10. PMID: 31598859.

[2]Gamma Rays: Horikawa DD, Sakashita T, Katagiri C, Watanabe M, Kikawada T, Nakahara Y, Hamada N, Wada S, Funayama T, Higashi S, Kobayashi Y, Okuda T, Kuwabara M. Radiation tolerance in the tardigrade Milnesium tardigradum. Int J Radiat Biol. 2006 Dec;82(12):843-8. doi: 10.1080/09553000600972956. PMID: 17178624.

[3]Hashimoto, T., Horikawa, D., Saito, Y. et al. Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein. Nat Commun 7, 12808 (2016). https://doi.org/10.1038/ncomms12808

Cancer control in long-lived mammals

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RG
Ruby Grewal Dec 11, 2020

[1]Kowalczyk A, Partha R, Clark NL, Chikina M. Pan-mammalian analysis of molecular constraints underlying extended lifespan. Elife. 2020 Feb 11;9:e51089. doi: 10.7554/eLife.51089. PMID: 32043462; PMCID: PMC7012612.

[2]Camps M, Herman A, Loh E, Loeb LA. Genetic constraints on protein evolution. Crit Rev Biochem Mol Biol. 2007;42(5):313-326. doi:10.1080/10409230701597642

[3]Guterres AN, Villanueva J. Targeting telomerase for cancer therapy. Oncogene. 2020 Sep;39(36):5811-5824. doi: 10.1038/s41388-020-01405-w. Epub 2020 Jul 30. PMID: 32733068; PMCID: PMC7678952.

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Shubhankar Kulkarni
Shubhankar Kulkarnia month ago
Thank you for your contribution Ruby Grewal ! The results from the first paper you cited certainly propose a reason (answer Peto's paradox at least partly) for Peto's paradox. Along with a high copy number of tumor suppressor gene P53 (in elephants), evolved gene networks can help in retraining inflammation and promoting DNA repair and NFKB-related pathways, like you suggested.

The immortal flatworm

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Brett M.
Brett M. Nov 26, 2020
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Shubhankar Kulkarni
Shubhankar Kulkarni2 months ago
Thank you for the contribution, Brett Melanson ! Certainly, there seems to be great potential here that can be tapped using CRISPR technology. Humans have genes that are similar to the ones that help in regeneration in the Planaria.
1. Smed-rpa-1 - similar to human Replication Protein A1 (RPA1). RPA1 is required for DNA replication, and suppression of Smed-rpa1 led to decreased mitotic activity adult planarians. [1]
2. Smed-rplp0 - similar to human Ribosomal Protein, large, P0
3. Smed-cdc23 - similar to human CDC23
4. Smed-cyclinL1 - similar to human Cyclin L1[2]
5. setd8-1 is required for the persistence of cell division in growing colonies - human SETD8/PR-SET7 (an H4K20me1 lysine methyltransferase) is required for cell cycle progression. [3]
6. Smed-vasa-1 - similar to human Vasa proteins. It helps in planarian stem cell regulation. [2]

References:
1. Reddien PW, Bermange AL, Murfitt KJ, Jennings JR, Sánchez Alvarado A. Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria. Dev Cell. 2005 May;8(5):635-49. doi: 10.1016/j.devcel.2005.02.014. PMID: 15866156; PMCID: PMC2267917.
2. Wagner DE, Ho JJ, Reddien PW. Genetic regulators of a pluripotent adult stem cell system in planarians identified by RNAi and clonal analysis. Cell Stem Cell. 2012;10(3):299-311. doi:10.1016/j.stem.2012.01.016
3. Oda H, Okamoto I, Murphy N, Chu J, Price SM, Shen MM, Torres-Padilla ME, Heard E, Reinberg D. Monomethylation of histone H4-lysine 20 is involved in chromosome structure and stability and is essential for mouse development. Mol Cell Biol. 2009 Apr;29(8):2278-95. doi: 10.1128/MCB.01768-08. Epub 2009 Feb 17. PMID: 19223465; PMCID: PMC2663305.

Hydra is in an unending growth phase

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Shubhankar Kulkarni
Shubhankar Kulkarni Oct 16, 2020

[1]Dańko MJ, Kozłowski J, Schaible R. Unraveling the non-senescence phenomenon in Hydra. J Theor Biol [Internet]. 2015 Oct;382:137–49. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022519315003227

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Darko Savic
Darko Savica month ago
If someday in the distant future we were to function in a similar manner I imagine our cardio-vasculature and intestines would have to be flawless first. Most of our cells would be shed through it.

Also, we would have to figure out a way to retain memories while shedding brain cells.
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Shubhankar Kulkarni
Shubhankar Kulkarnia month ago
Darko Savic The latter part of your comment is the trickiest. The "fresh" cells need to have the exact same connections in order to replace the original cell. I think rejuvenating the existing cell will be the most feasible way, currently.
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Darko Savic
Darko Savica month ago
Shubhankar Kulkarni or if we figure out a way to save our memories digitally and re-upload them on demand. Then we could just accept the fact that we are dynamic, ever-changing beings in every sense, including personality, memories, etc. The changes would be gradual, pretty much as they are now. You would be a different person every few decades. A moving average:)

The oldest koi

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Deru Xu
Deru Xu Oct 28, 2020

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