Killifish as an aging animal model - Revision history

Andrea: Added ref to /* Limitations of killifish */

2023-07-03T11:23:42Z

Added ref to Limitations of killifish

← Older revision		Revision as of 11:23, 3 July 2023
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	Whilst killifish can be a great alternative compared to more conventional animal models, they also suppose some limitations:		Whilst killifish can be a great alternative compared to more conventional animal models, they also suppose some limitations:

	*Teleost fish such as killifish, which includes a large and very diverse group of ray-finned fishes, all possess a duplicated genome. This whole-genome duplication (WGD) occurred in an ancient common ancestor of all teleost fishes. Duplicated genes may sometimes serve different functions or lead to the non-functionalization of one of the genes.<ref>Glasauer, S., & Neuhauss, S. (2014). Whole-genome duplication in teleost fishes and its evolutionary consequences. ''Molecular Genetics And Genomics'', ''289''(6), 1045-1060. doi: 10.1007/s00438-014-0889-2</ref> This WGD might have occurred at least twice during evolution and may have led to highly fish-specific adaptations.<ref>Dehal, P., & Boore, J. (2005). Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate. ''Plos Biology'', ''3''(10), e314. doi: 10.1371/journal.pbio.0030314</ref> This poses significant limitations on findings derived from killifishes. Recent studies suggest that evolutionarily ~~recent~~ changes in chromatin accessibility in ancient gene duplications have allowed killifish to develop mechanisms of suspended animation at embryonic stages in order to survive extreme environments.		*Teleost fish such as killifish, which includes a large and very diverse group of ray-finned fishes, all possess a duplicated genome. This whole-genome duplication (WGD) occurred in an ancient common ancestor of all teleost fishes. Duplicated genes may sometimes serve different functions or lead to the non-functionalization of one of the genes.<ref>Glasauer, S., & Neuhauss, S. (2014). Whole-genome duplication in teleost fishes and its evolutionary consequences. ''Molecular Genetics And Genomics'', ''289''(6), 1045-1060. doi: 10.1007/s00438-014-0889-2</ref> This WGD might have occurred at least twice during evolution and may have led to highly fish-specific adaptations.<ref>Dehal, P., & Boore, J. (2005). Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate. ''Plos Biology'', ''3''(10), e314. doi: 10.1371/journal.pbio.0030314</ref> This poses significant limitations on findings derived from killifishes. Recent studies suggest that recent evolutionarily changes in chromatin accessibility at ancient gene duplications events have allowed killifish to develop mechanisms of suspended animation at embryonic stages in order to survive to extreme environments.<ref>Singh, P. P., Reeves, G. A., Contrepois, K., Ellenberger, M., Hu, C. K., Snyder, M. P., & Brunet, A. (2021). Evolution of diapause in the African turquoise killifish by remodeling ancient gene regulatory landscape. ''bioRxiv'', 2021-10.</ref>
	*Each killifish requires approximately 1 liter of water.<ref>Dodzian, J., Kean, S., Seidel, J., & Valenzano, D. (2018). A Protocol for Laboratory Housing of Turquoise Killifish (&lt;em&gt;Nothobranchius furzeri&lt;/em&gt;). ''Journal Of Visualized Experiments'', (134). doi: 10.3791/57073</ref> This aspect becomes very troublesome for high throughput assays when taking into account space logistics. However, these restrictions apply mostly when keeping individuals in social isolation, and more killifish per liter could be housed in groups. On the other hand, this might prohibit pharmacological approaches, given that incredibly large amounts of drugs would need to be diluted into 1L of water to potentially have an effect.		*Each killifish requires approximately 1 liter of water.<ref>Dodzian, J., Kean, S., Seidel, J., & Valenzano, D. (2018). A Protocol for Laboratory Housing of Turquoise Killifish (&lt;em&gt;Nothobranchius furzeri&lt;/em&gt;). ''Journal Of Visualized Experiments'', (134). doi: 10.3791/57073</ref> This aspect becomes very troublesome for high throughput assays when taking into account space logistics. However, these restrictions apply mostly when keeping individuals in social isolation, and more killifish per liter could potentially be housed in groups. On the other hand, this might prohibit pharmacological approaches, given that incredibly large amounts of drugs would need to be diluted into 1L of water to potentially have an effect.

	==References==		==References==

Andrea: /* Literature update Limitations of killifish */

2023-07-03T11:20:05Z

Literature update Limitations of killifish

← Older revision		Revision as of 11:20, 3 July 2023
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	Due to alternating dry and rainy seasons, these regions have pronounced seasonal differences in water availability, causing the turquoise killifish to inhabit reservoirs of water that fill up during short rainy seasons and dry out entirely during the longer dry seasons.		Due to alternating dry and rainy seasons, these regions have pronounced seasonal differences in water availability, causing the turquoise killifish to inhabit reservoirs of water that fill up during short rainy seasons and dry out entirely during the longer dry seasons.

	To survive as a species, the turquoise killifish has developed a unique annual life cycle in which it can persist periods of drought through an extended period of embryonic stasis called diapause.<ref>Poeschla, M., & Valenzano, D. R. (2020). The turquoise killifish: A genetically tractable model for the study of aging. ''Journal of Experimental Biology'', ''223''(Suppl_1), jeb209296. https://doi.org/10.1242/jeb.209296</ref> With the onset of the wet season, the turquoise killifish then switches to a mode of explosive growth and sexual maturation, resulting in females laying up to 120 eggs per day.<ref>Vrtílek, M., & Reichard, M. (2016). Female fecundity traits in wild populations of African annual fish: the role of the aridity gradient. ''Ecology and Evolution'', ''6''(16), 5921–5931. https://doi.org/10.1002/ece3.2337</ref>		To survive as a species, the turquoise killifish has developed a unique annual life cycle in which it can persist periods of drought through an extended period of embryonic stasis called diapause.<ref>Poeschla, M., & Valenzano, D. R. (2020). The turquoise killifish: A genetically tractable model for the study of aging. ''Journal of Experimental Biology'', ''223''(Suppl_1), jeb209296. https://doi.org/10.1242/jeb.209296</ref> With the onset of the wet season, the turquoise killifish then switches to a mode of explosive growth and sexual maturation, resulting in females laying up to 120 eggs per day.<ref>Vrtílek, M., & Reichard, M. (2016). Female fecundity traits in wild populations of African annual fish: the role of the aridity gradient. ''Ecology and Evolution'', ''6''(16), [tel:5921–5931 5921–5931]. https://doi.org/10.1002/ece3.2337</ref>

	The process from hatching to sexually mature fish takes no more than 14 days, making it the fastest known rate of sexual maturation for vertebrates.<ref name=":2">Vrtílek, M., Žák, J., Pšenička, M., & Reichard, M. (2018). Extremely rapid maturation of a wild African annual fish. ''Current Biology'', ''28''(15), R822–R824. https://doi.org/10.1016/j.cub.2018.06.031</ref> Subsequently, the fertilized eggs enter the diapause state to endure the following dry season, and the circle starts again. As a result of this annual life cycle, the turquoise killifish has a short adult lifespan of four to eight months and displays aging-related transformations like lose of body colour and specific patterning (''see section'' [https://en.longevitywiki.org/index.php?title=Killifish_as_an_Aging_Animal_Model#Aging_features Aging features]).		The process from hatching to sexually mature fish takes no more than 14 days, making it the fastest known rate of sexual maturation for vertebrates.<ref name=":2">Vrtílek, M., Žák, J., Pšenička, M., & Reichard, M. (2018). Extremely rapid maturation of a wild African annual fish. ''Current Biology'', ''28''(15), R822–R824. https://doi.org/10.1016/j.cub.2018.06.031</ref> Subsequently, the fertilized eggs enter the diapause state to endure the following dry season, and the circle starts again. As a result of this annual life cycle, the turquoise killifish has a short adult lifespan of four to eight months and displays aging-related transformations like lose of body colour and specific patterning (''see section'' [https://en.longevitywiki.org/index.php?title=Killifish_as_an_Aging_Animal_Model#Aging_features Aging features]).
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	===Replicative senescence===		===Replicative senescence===
	After a certain number of replications, cells enter a state of growth arrest and altered function called [[Cellular senescence\|replicative senescence]]. Replicative senescence is considered a [[Hallmarks of aging\|hallmark of aging]], and senescent cells can be detected by markers such as the appearance of senescence-associated β-galactosidase (β-GAL).<ref>Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. ''Proceedings of the National Academy of Sciences of the United States of America'', ''92''(20), 9363–9367. https://doi.org/10.1073%2Fpnas.92.20.9363</ref> Old killifish show increased β-GAL activity,<ref name=":8" /><ref name=":12" /> which is attenuated with lifespan-extending interventions like lowering water temperature.<ref name=":9" />		After a certain number of replications, cells enter a state of growth arrest and altered function called [[Cellular senescence\|replicative senescence]]. Replicative senescence is considered a [[Hallmarks of aging\|hallmark of aging]], and senescent cells can be detected by markers such as the appearance of senescence-associated β-galactosidase (β-GAL).<ref>Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. ''Proceedings of the National Academy of Sciences of the United States of America'', ''92''(20), [tel:9363–9367 9363–9367]. https://doi.org/10.1073%2Fpnas.92.20.9363</ref> Old killifish show increased β-GAL activity,<ref name=":8" /><ref name=":12" /> which is attenuated with lifespan-extending interventions like lowering water temperature.<ref name=":9" />

	==Animal model for aging research==		==Animal model for aging research==
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	Whilst killifish can be a great alternative compared to more conventional animal models, they also suppose some limitations:		Whilst killifish can be a great alternative compared to more conventional animal models, they also suppose some limitations:

	*Teleost fish such as killifish, which includes a large and very diverse group of ray-finned fishes, all possess a duplicated genome. This whole-genome duplication (WGD) occurred in an ancient common ancestor of all teleost fishes. Duplicated genes may sometimes serve different functions or lead to the non-functionalization of one of the genes.<ref>Glasauer, S., & Neuhauss, S. (2014). Whole-genome duplication in teleost fishes and its evolutionary consequences. ''Molecular Genetics And Genomics'', ''289''(6), 1045-1060. doi: 10.1007/s00438-014-0889-2</ref> This WGD might have occurred at least twice during evolution and may have led to highly fish-specific adaptations.<ref>Dehal, P., & Boore, J. (2005). Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate. ''Plos Biology'', ''3''(10), e314. doi: 10.1371/journal.pbio.0030314</ref> This poses significant limitations on findings derived from killifishes.		*Teleost fish such as killifish, which includes a large and very diverse group of ray-finned fishes, all possess a duplicated genome. This whole-genome duplication (WGD) occurred in an ancient common ancestor of all teleost fishes. Duplicated genes may sometimes serve different functions or lead to the non-functionalization of one of the genes.<ref>Glasauer, S., & Neuhauss, S. (2014). Whole-genome duplication in teleost fishes and its evolutionary consequences. ''Molecular Genetics And Genomics'', ''289''(6), 1045-1060. doi: 10.1007/s00438-014-0889-2</ref> This WGD might have occurred at least twice during evolution and may have led to highly fish-specific adaptations.<ref>Dehal, P., & Boore, J. (2005). Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate. ''Plos Biology'', ''3''(10), e314. doi: 10.1371/journal.pbio.0030314</ref> This poses significant limitations on findings derived from killifishes. Recent studies suggest that evolutionarily recent changes in chromatin accessibility in ancient gene duplications have allowed killifish to develop mechanisms of suspended animation at embryonic stages in order to survive extreme environments.
	*Each killifish requires approximately 1 liter of water.<ref>Dodzian, J., Kean, S., Seidel, J., & Valenzano, D. (2018). A Protocol for Laboratory Housing of Turquoise Killifish (&lt;em&gt;Nothobranchius furzeri&lt;/em&gt;). ''Journal Of Visualized Experiments'', (134). doi: 10.3791/57073</ref> This aspect becomes very troublesome for high throughput assays when taking into account space logistics. ~~Furthermore~~, ~~it may even~~ prohibit pharmacological approaches, given that incredibly large amounts of drugs would need to be diluted in 1L of water to potentially have an effect.		*Each killifish requires approximately 1 liter of water.<ref>Dodzian, J., Kean, S., Seidel, J., & Valenzano, D. (2018). A Protocol for Laboratory Housing of Turquoise Killifish (&lt;em&gt;Nothobranchius furzeri&lt;/em&gt;). ''Journal Of Visualized Experiments'', (134). doi: 10.3791/57073</ref> This aspect becomes very troublesome for high throughput assays when taking into account space logistics. However, these restrictions apply mostly when keeping individuals in social isolation, and more killifish per liter could be housed in groups. On the other hand, this might prohibit pharmacological approaches, given that incredibly large amounts of drugs would need to be diluted into 1L of water to potentially have an effect.

	==References==		==References==

Andrea: category change

2022-12-27T12:37:46Z

category change

← Older revision		Revision as of 12:37, 27 December 2022
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	==References==		==References==
	<references />		<references />
	[[Category:~~Longevity~~]]		[[Category:Main list]]
	[[Category:~~Drafts~~]]		[[Category:Tools to study aging]]

Andrea: /* hyperlinked to new page */

2022-10-10T18:38:08Z

hyperlinked to new page

← Older revision		Revision as of 18:38, 10 October 2022
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	The group led by Anne Brunet in Stanford University has developed a genotype-to-phenotype platform using de-novo-assembled genome and CRISPR/Cas9 technology, which allows for high-throughput and high efficiency knock-out and knock-in studies in killifish.<ref name=":15">Harel, I., Benayoun, B., Machado, B., Singh, P., Hu, C., & Pech, M. et al. (2015). A Platform for Rapid Exploration of Aging and Diseases in a Naturally Short-Lived Vertebrate. ''Cell'', ''160''(5), 1013-1026. doi: 10.1016/j.cell.2015.01.038</ref>		The group led by Anne Brunet in Stanford University has developed a genotype-to-phenotype platform using de-novo-assembled genome and CRISPR/Cas9 technology, which allows for high-throughput and high efficiency knock-out and knock-in studies in killifish.<ref name=":15">Harel, I., Benayoun, B., Machado, B., Singh, P., Hu, C., & Pech, M. et al. (2015). A Platform for Rapid Exploration of Aging and Diseases in a Naturally Short-Lived Vertebrate. ''Cell'', ''160''(5), 1013-1026. doi: 10.1016/j.cell.2015.01.038</ref>

	A key tool for generating transgenic species in fish is the transposase system. Transposon elements (TE) are genes capable of changing position within the genome, which can sometimes result in ''de novo'' mutations or changes in genome size.<ref>Bourque, G., Burns, K., Gehring, M., Gorbunova, V., Seluanov, A., & Hammell, M. et al. (2018). Ten things you should know about transposable elements. ''Genome Biology'', ''19''(1). doi: 10.1186/s13059-018-1577-z</ref> Transposase enzymes bind to the end of TE and catalyze their movement to other parts of the genome. In killifish, the Tol2 transposase system has been adapted from other model animals by Valenzano to integrate genes of interest into the host's genome in a stable and efficient manner.<ref>Valenzano, D., Sharp, S., & Brunet, A. (2011). Transposon-Mediated Transgenesis in the Short-Lived African KillifishNothobranchius furzeri, a Vertebrate Model for Aging. ''G3 Genes\|Genomes\|Genetics'', ''1''(7), 531-538. doi: 10.1534/g3.111.001271</ref>		A key tool for generating transgenic species in fish is the transposase system. [[Transposons in aging\|Transposon elements]] (TE) are genes capable of changing position within the genome, which can sometimes result in ''de novo'' mutations or changes in genome size.<ref>Bourque, G., Burns, K., Gehring, M., Gorbunova, V., Seluanov, A., & Hammell, M. et al. (2018). Ten things you should know about transposable elements. ''Genome Biology'', ''19''(1). doi: 10.1186/s13059-018-1577-z</ref> Transposase enzymes bind to the end of TE and catalyze their movement to other parts of the genome. In killifish, the Tol2 transposase system has been adapted from other model animals by Valenzano to integrate genes of interest into the host's genome in a stable and efficient manner.<ref>Valenzano, D., Sharp, S., & Brunet, A. (2011). Transposon-Mediated Transgenesis in the Short-Lived African KillifishNothobranchius furzeri, a Vertebrate Model for Aging. ''G3 Genes\|Genomes\|Genetics'', ''1''(7), 531-538. doi: 10.1534/g3.111.001271</ref>

	Additional progress has been made in developing other genetic tools for killifish. <ref>Harel, I., Valenzano, D., & Brunet, A. (2016). Efficient genome engineering approaches for the short-lived African turquoise killifish. ''Nature Protocols'', ''11''(10), 2010-2028. doi: 10.1038/nprot.2016.103</ref><ref>Platzer, M., & Englert, C. (2016). Nothobranchius furzeri: A Model for Aging Research and More. ''Trends In Genetics'', ''32''(9), 543-552. doi: 10.1016/j.tig.2016.06.006</ref> Due to the fast life cycle of killifish, new stable transgenic lines can be generated as rapidly as in 2 to 3 months.<ref name=":15" />		Additional progress has been made in developing other genetic tools for killifish. <ref>Harel, I., Valenzano, D., & Brunet, A. (2016). Efficient genome engineering approaches for the short-lived African turquoise killifish. ''Nature Protocols'', ''11''(10), 2010-2028. doi: 10.1038/nprot.2016.103</ref><ref>Platzer, M., & Englert, C. (2016). Nothobranchius furzeri: A Model for Aging Research and More. ''Trends In Genetics'', ''32''(9), 543-552. doi: 10.1016/j.tig.2016.06.006</ref> Due to the fast life cycle of killifish, new stable transgenic lines can be generated as rapidly as in 2 to 3 months.<ref name=":15" />

Andrea: removed draft banner and small edits

2022-09-20T09:03:43Z

removed draft banner and small edits

← Older revision		Revision as of 09:03, 20 September 2022
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	~~{{Draft-article}}~~[[File:Nothobranchius furzeri GRZ thumb.jpg\|thumb\|Male ''Nothobranchius furzeri'', also known as the turquoise killifish.<ref>https://en.wikipedia.org/wiki/Nothobranchius_furzeri</ref>\|231x231px]]The African turquoise killifish (''Nothobranchius furzeri'') is the shortest lived vertebrate known to date, with a median lifespan of only 4 to 8 months. This short lifespan is closer to that of unicellular and invertebrate research organisms (such as the fruit fly) than to vertebrate research organisms such as mice or zebrafish.<ref name=":0">Hu, C., & Brunet, A. (2018). The African turquoise killifish: A research organism to study vertebrate aging and diapause. ''Aging Cell'', ''17''(3), e12757. [https://doi.org/10.1111/acel.12757 doi: 10.1111/acel.12757]</ref> This places the Turquoise Killifish in the unique position of allowing high repeatability and feasibility for experiments, whilst better recapitulating human aging traits.		[[File:Nothobranchius furzeri GRZ thumb.jpg\|thumb\|Male ''Nothobranchius furzeri'', also known as the turquoise killifish.<ref>https://en.wikipedia.org/wiki/Nothobranchius_furzeri</ref>\|231x231px]]The African turquoise killifish (''Nothobranchius furzeri'') is the shortest lived vertebrate known to date, with a median lifespan of only 4 to 8 months. This short lifespan is closer to that of unicellular and invertebrate research organisms (such as the fruit fly) than to vertebrate research organisms such as mice or zebrafish.<ref name=":0">Hu, C., & Brunet, A. (2018). The African turquoise killifish: A research organism to study vertebrate aging and diapause. ''Aging Cell'', ''17''(3), e12757. [https://doi.org/10.1111/acel.12757 doi: 10.1111/acel.12757]</ref> This places the Turquoise Killifish in the unique position of allowing high repeatability and feasibility for experiments, whilst better recapitulating human aging traits.

	==Habitat and life cycle of the turquoise killifish==		==Habitat and life cycle of the turquoise killifish==
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	Although no sex-dependent difference in life expectancy is found in captivity<ref name=":1" /><ref name=":4" /><ref name=":6">Valenzano, Dario R., Eva Terzibasi, Tyrone Genade, Antonino Cattaneo, Luciano Domenici, and Alessandro Cellerino. 2006. ‘Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate’. ''Current Biology'' 16(3):296–300. https://doi.org/10.1016/j.cub.2005.12.038</ref>, significant differences in sex ratios are observed in the wild<ref>Reichard, M., M. Polačik, and O. Sedláček. 2009. ‘Distribution, Colour Polymorphism and Habitat Use of the African Killifish Nothobranchius Furzeri, the Vertebrate with the Shortest Life Span’. ''Journal of Fish Biology'' 74(1):198–212. https://doi.org/10.1111/j.1095-8649.2008.02129.x</ref>. During the rainy season, the proportion of the male population decreases, so that after three months at least two thirds of the population are female.<ref>Vrtílek, Milan, Jakub Žák, Matej Polačik, Radim Blažek, and Martin Reichard. 2018. ‘Longitudinal Demographic Study of Wild Populations of African Annual Killifish’. ''Scientific Reports'' 8(1):4774. https://doi.org/10.1038/s41598-018-22878-6</ref>		Although no sex-dependent difference in life expectancy is found in captivity<ref name=":1" /><ref name=":4" /><ref name=":6">Valenzano, Dario R., Eva Terzibasi, Tyrone Genade, Antonino Cattaneo, Luciano Domenici, and Alessandro Cellerino. 2006. ‘Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate’. ''Current Biology'' 16(3):296–300. https://doi.org/10.1016/j.cub.2005.12.038</ref>, significant differences in sex ratios are observed in the wild<ref>Reichard, M., M. Polačik, and O. Sedláček. 2009. ‘Distribution, Colour Polymorphism and Habitat Use of the African Killifish Nothobranchius Furzeri, the Vertebrate with the Shortest Life Span’. ''Journal of Fish Biology'' 74(1):198–212. https://doi.org/10.1111/j.1095-8649.2008.02129.x</ref>. During the rainy season, the proportion of the male population decreases, so that after three months at least two thirds of the population are female.<ref>Vrtílek, Milan, Jakub Žák, Matej Polačik, Radim Blažek, and Martin Reichard. 2018. ‘Longitudinal Demographic Study of Wild Populations of African Annual Killifish’. ''Scientific Reports'' 8(1):4774. https://doi.org/10.1038/s41598-018-22878-6</ref>

	[[Calorie restriction\|Dietary restriction]] can increase ~~the~~ maximum lifespan ~~for~~ both the short-lived GRZ laboratory strain and the longer-lived wild-derived strain MZM-04/10P.<ref name=":10" /> However, in the wild strain MZM-04/10P, lifespan extension is associated with increased baseline mortality.<ref name=":10" /> In addition to dietary restriction, lowering the water temperature also ~~increased the~~ median lifespan significantly.<ref name=":9" />		[[Calorie restriction\|Dietary restriction]] can increase maximum lifespan of both the short-lived GRZ laboratory strain and the longer-lived wild-derived strain MZM-04/10P.<ref name=":10" /> However, in the wild strain MZM-04/10P, lifespan extension is associated with increased baseline mortality.<ref name=":10" /> In addition to dietary restriction, lowering the water temperature can also increase median lifespan significantly.<ref name=":9" /> This demonstrates that lifespan is malleable in killifish when subjecting them to specific interventions, as similarly observed in other animal models.
	==Aging features==		==Aging features==

Wurstuk: Added short paragraph to lifespan about lifespan extension.

2022-09-17T18:06:59Z

Added short paragraph to lifespan about lifespan extension.

← Older revision		Revision as of 18:06, 17 September 2022
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	Although no sex-dependent difference in life expectancy is found in captivity<ref name=":1" /><ref name=":4" /><ref name=":6">Valenzano, Dario R., Eva Terzibasi, Tyrone Genade, Antonino Cattaneo, Luciano Domenici, and Alessandro Cellerino. 2006. ‘Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate’. ''Current Biology'' 16(3):296–300. https://doi.org/10.1016/j.cub.2005.12.038</ref>, significant differences in sex ratios are observed in the wild<ref>Reichard, M., M. Polačik, and O. Sedláček. 2009. ‘Distribution, Colour Polymorphism and Habitat Use of the African Killifish Nothobranchius Furzeri, the Vertebrate with the Shortest Life Span’. ''Journal of Fish Biology'' 74(1):198–212. https://doi.org/10.1111/j.1095-8649.2008.02129.x</ref>. During the rainy season, the proportion of the male population decreases, so that after three months at least two thirds of the population are female.<ref>Vrtílek, Milan, Jakub Žák, Matej Polačik, Radim Blažek, and Martin Reichard. 2018. ‘Longitudinal Demographic Study of Wild Populations of African Annual Killifish’. ''Scientific Reports'' 8(1):4774. https://doi.org/10.1038/s41598-018-22878-6</ref>		Although no sex-dependent difference in life expectancy is found in captivity<ref name=":1" /><ref name=":4" /><ref name=":6">Valenzano, Dario R., Eva Terzibasi, Tyrone Genade, Antonino Cattaneo, Luciano Domenici, and Alessandro Cellerino. 2006. ‘Resveratrol Prolongs Lifespan and Retards the Onset of Age-Related Markers in a Short-Lived Vertebrate’. ''Current Biology'' 16(3):296–300. https://doi.org/10.1016/j.cub.2005.12.038</ref>, significant differences in sex ratios are observed in the wild<ref>Reichard, M., M. Polačik, and O. Sedláček. 2009. ‘Distribution, Colour Polymorphism and Habitat Use of the African Killifish Nothobranchius Furzeri, the Vertebrate with the Shortest Life Span’. ''Journal of Fish Biology'' 74(1):198–212. https://doi.org/10.1111/j.1095-8649.2008.02129.x</ref>. During the rainy season, the proportion of the male population decreases, so that after three months at least two thirds of the population are female.<ref>Vrtílek, Milan, Jakub Žák, Matej Polačik, Radim Blažek, and Martin Reichard. 2018. ‘Longitudinal Demographic Study of Wild Populations of African Annual Killifish’. ''Scientific Reports'' 8(1):4774. https://doi.org/10.1038/s41598-018-22878-6</ref>

			[[Calorie restriction\|Dietary restriction]] can increase the maximum lifespan for both the short-lived GRZ laboratory strain and the longer-lived wild-derived strain MZM-04/10P.<ref name=":10" /> However, in the wild strain MZM-04/10P, lifespan extension is associated with increased baseline mortality.<ref name=":10" /> In addition to dietary restriction, lowering the water temperature also increased the median lifespan significantly.<ref name=":9" />
	==Aging features==		==Aging features==

Andrea: /* Genetic tools available */

2022-09-13T13:59:07Z

Genetic tools available

← Older revision		Revision as of 13:59, 13 September 2022
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	==Animal model for aging research==		==Animal model for aging research==
	[[File:The African turquoise killifish as a novel animal model to study aging.jpg\|thumb\|The African turquoise killifish as a novel animal model to study aging. Being a vertebrate with a short lifespan of 4-6 months places the killifish in an unique position to study aging.<ref name=":0" />]]Dr Dario Valenzano, trained at Brunet lab in Stanford and currently at the Leibniz Institute on Aging, is especially known for his ~~characterisation of~~ the turquoise killifish. He is considered to have established this species as a novel research model and as an aging animal model.		[[File:The African turquoise killifish as a novel animal model to study aging.jpg\|thumb\|The African turquoise killifish as a novel animal model to study aging. Being a vertebrate with a short lifespan of 4-6 months places the killifish in an unique position to study aging.<ref name=":0" />]]Dr Dario Valenzano, trained at Brunet lab in Stanford and currently at the Leibniz Institute on Aging, is especially known for his contribution in characterising the turquoise killifish. He is considered to have established this species as a novel research model and as an aging animal model.

	One of the main advantages of using killifish as an aging animal model is its close resemblance to human aging, usually seen in much longer lived animal models such as mice and zebrafish, and its short lifespan of 4 to 8 months, which allows for greater experimental scalability.<ref name=":02">Hu, C., & Brunet, A. (2018). The African turquoise killifish: A research organism to study vertebrate aging and diapause. ''Aging Cell'', ''17''(3), e12757. [https://doi.org/10.1111/acel.12757 doi: 10.1111/acel.12757]</ref>		One of the main advantages of using killifish as an aging animal model is its close resemblance to human aging, usually seen in much longer lived animal models such as mice and zebrafish, and its short lifespan of 4 to 8 months, which allows for greater experimental scalability.<ref name=":02">Hu, C., & Brunet, A. (2018). The African turquoise killifish: A research organism to study vertebrate aging and diapause. ''Aging Cell'', ''17''(3), e12757. [https://doi.org/10.1111/acel.12757 doi: 10.1111/acel.12757]</ref>

			The turquoise killifish has been recently established as a model for [[Aging and eye disease\|age-related eye disease]].<ref name=":14">Vanhunsel, S., Bergmans, S., Beckers, A., Etienne, I., Van houcke, J., & Seuntjens, E. et al. (2021). The killifish visual system as an in vivo model to study brain aging and rejuvenation. ''Npj Aging And Mechanisms Of Disease'', ''7''(1). doi: 10.1038/s41514-021-00077-4</ref> Considering vision decline as a conserved aging hallmark, the aging-associated decline of the killifish visual system has been proposed as a useful ''in vivo'' model to study brain aging and rejuvenation.<ref name=":14" />

	====Genetic tools available====		====Genetic tools available====
	~~https~~://~~onlinelibrary~~.~~wiley~~.~~com~~/doi/10.~~1111~~/~~acel~~.~~12757~~		The group led by Anne Brunet in Stanford University has developed a genotype-to-phenotype platform using de-novo-assembled genome and CRISPR/Cas9 technology, which allows for high-throughput and high efficiency knock-out and knock-in studies in killifish.<ref name=":15">Harel, I., Benayoun, B., Machado, B., Singh, P., Hu, C., & Pech, M. et al. (2015). A Platform for Rapid Exploration of Aging and Diseases in a Naturally Short-Lived Vertebrate. ''Cell'', ''160''(5), 1013-1026. doi: 10.1016/j.cell.2015.01.038</ref>

			A key tool for generating transgenic species in fish is the transposase system. Transposon elements (TE) are genes capable of changing position within the genome, which can sometimes result in ''de novo'' mutations or changes in genome size.<ref>Bourque, G., Burns, K., Gehring, M., Gorbunova, V., Seluanov, A., & Hammell, M. et al. (2018). Ten things you should know about transposable elements. ''Genome Biology'', ''19''(1). doi: 10.1186/s13059-018-1577-z</ref> Transposase enzymes bind to the end of TE and catalyze their movement to other parts of the genome. In killifish, the Tol2 transposase system has been adapted from other model animals by Valenzano to integrate genes of interest into the host's genome in a stable and efficient manner.<ref>Valenzano, D., Sharp, S., & Brunet, A. (2011). Transposon-Mediated Transgenesis in the Short-Lived African KillifishNothobranchius furzeri, a Vertebrate Model for Aging. ''G3 Genes\|Genomes\|Genetics'', ''1''(7), 531-538. doi: 10.1534/g3.111.001271</ref>

	~~====Killifish as a model to study brain aging====~~		Additional progress has been made in developing other genetic tools for killifish. <ref>Harel, I., Valenzano, D., & Brunet, A. (2016). Efficient genome engineering approaches for the short-lived African turquoise killifish. ''Nature Protocols'', ''11''(10), 2010-2028. doi: 10.1038/nprot.2016.103</ref><ref>Platzer, M., & Englert, C. (2016). Nothobranchius furzeri: A Model for Aging Research and More. ''Trends In Genetics'', ''32''(9), 543-552. doi: 10.1016/j.tig.2016.06.006</ref> Due to the fast life cycle of killifish, new stable transgenic lines can be generated as rapidly as in 2 to 3 months.<ref name=":15" />
	~~The~~ killifish ~~visual system as an in vivo model to study brain aging and rejuvenation:https~~://~~www~~.~~ncbi~~.~~nlm~~.~~nih~~.~~gov~~/~~pmc~~/~~articles/PMC8371010~~/

	==Limitations of killifish==		==Limitations of killifish==

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	Lipofuscin, or age pigment, is an autofluorescent pigment that accumulates progressively with age within the cells of many species.<ref>Brunk, U. T., Jones, C. B., & Sohal, R. S. (1992). A novel hypothesis of lipofuscinogenesis and cellular aging based on interactions between oxidative stress and autophagocytosis. ''Mutation Research'', ''275''(3–6), 395–403. https://doi.org/10.1016/0921-8734(92)90042-n</ref> In old killifish, elevated lipofuscin levels are detected in various cell types such as heart and liver cells.<ref name=":7" /><ref name=":8" /><ref name=":12">Ahuja et al. (2019). Loss of genomic integrity induced by lysosphingolipid imbalance drives ageing in the heart. ''EMBO Reports'', ''20''(4), e47407. https://doi.org/10.15252/embr.201847407</ref> Thereby, lipofuscin accumulation is faster in the short-lived strain GRZ than in the longer-lived strain MZM0403, suggesting that the short lifespan of the GRZ strain is associated with faster histological aging.<ref name=":7" />		Lipofuscin, or age pigment, is an autofluorescent pigment that accumulates progressively with age within the cells of many species.<ref>Brunk, U. T., Jones, C. B., & Sohal, R. S. (1992). A novel hypothesis of lipofuscinogenesis and cellular aging based on interactions between oxidative stress and autophagocytosis. ''Mutation Research'', ''275''(3–6), 395–403. https://doi.org/10.1016/0921-8734(92)90042-n</ref> In old killifish, elevated lipofuscin levels are detected in various cell types such as heart and liver cells.<ref name=":7" /><ref name=":8" /><ref name=":12">Ahuja et al. (2019). Loss of genomic integrity induced by lysosphingolipid imbalance drives ageing in the heart. ''EMBO Reports'', ''20''(4), e47407. https://doi.org/10.15252/embr.201847407</ref> Thereby, lipofuscin accumulation is faster in the short-lived strain GRZ than in the longer-lived strain MZM0403, suggesting that the short lifespan of the GRZ strain is associated with faster histological aging.<ref name=":7" />

	Lowering ~~the~~ water temperature from ~~25 °C~~ to ~~22 °C and~~ [[Calorie restriction\|dietary restriction]] ~~reduced~~ age-related lipofuscin accumulation in old killifish.<ref name=":9" /><ref name=":10" />		Lowering water temperature (for instance from 25°C to 22°C) as well as [[Calorie restriction\|dietary restriction]] can reduce age-related lipofuscin accumulation in old killifish.<ref name=":9" /><ref name=":10" />

	===Mitochondria===		===Mitochondria===

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Limitations of killifish

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	==Limitations of killifish==		==Limitations of killifish==
	Whilst killifish ~~are~~ a great alternative compared to more conventional animal models, they also suppose some limitations:		Whilst killifish can be a great alternative compared to more conventional animal models, they also suppose some limitations:

	*Teleost fish such as killifish, which includes a large and very diverse group of ray-finned fishes, all possess a duplicated genome. This whole-genome duplication (WGD) occurred in an ancient common ancestor of all teleost fishes. Duplicated genes may sometimes serve different functions or lead to the non-functionalization of one of the genes.<ref>Glasauer, S., & Neuhauss, S. (2014). Whole-genome duplication in teleost fishes and its evolutionary consequences. ''Molecular Genetics And Genomics'', ''289''(6), 1045-1060. doi: 10.1007/s00438-014-0889-2</ref> This WGD might have occurred at least twice during evolution and may have led to highly fish-specific adaptations.<ref>Dehal, P., & Boore, J. (2005). Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate. ''Plos Biology'', ''3''(10), e314. doi: 10.1371/journal.pbio.0030314</ref> This poses significant limitations on findings derived from killifishes.		*Teleost fish such as killifish, which includes a large and very diverse group of ray-finned fishes, all possess a duplicated genome. This whole-genome duplication (WGD) occurred in an ancient common ancestor of all teleost fishes. Duplicated genes may sometimes serve different functions or lead to the non-functionalization of one of the genes.<ref>Glasauer, S., & Neuhauss, S. (2014). Whole-genome duplication in teleost fishes and its evolutionary consequences. ''Molecular Genetics And Genomics'', ''289''(6), 1045-1060. doi: 10.1007/s00438-014-0889-2</ref> This WGD might have occurred at least twice during evolution and may have led to highly fish-specific adaptations.<ref>Dehal, P., & Boore, J. (2005). Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate. ''Plos Biology'', ''3''(10), e314. doi: 10.1371/journal.pbio.0030314</ref> This poses significant limitations on findings derived from killifishes.

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	*Teleost fish such as killifish, which includes a large and very diverse group of ray-finned fishes, all possess a duplicated genome. This whole-genome duplication (WGD) occurred in an ancient common ancestor of all teleost fishes. Duplicated genes may sometimes serve different functions or lead to the non-functionalization of one of the genes.<ref>Glasauer, S., & Neuhauss, S. (2014). Whole-genome duplication in teleost fishes and its evolutionary consequences. ''Molecular Genetics And Genomics'', ''289''(6), 1045-1060. doi: 10.1007/s00438-014-0889-2</ref> This WGD might have occurred at least twice during evolution and may have led to highly fish-specific adaptations.<ref>Dehal, P., & Boore, J. (2005). Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate. ''Plos Biology'', ''3''(10), e314. doi: 10.1371/journal.pbio.0030314</ref> This poses significant limitations on findings derived from killifishes.		*Teleost fish such as killifish, which includes a large and very diverse group of ray-finned fishes, all possess a duplicated genome. This whole-genome duplication (WGD) occurred in an ancient common ancestor of all teleost fishes. Duplicated genes may sometimes serve different functions or lead to the non-functionalization of one of the genes.<ref>Glasauer, S., & Neuhauss, S. (2014). Whole-genome duplication in teleost fishes and its evolutionary consequences. ''Molecular Genetics And Genomics'', ''289''(6), 1045-1060. doi: 10.1007/s00438-014-0889-2</ref> This WGD might have occurred at least twice during evolution and may have led to highly fish-specific adaptations.<ref>Dehal, P., & Boore, J. (2005). Two Rounds of Whole Genome Duplication in the Ancestral Vertebrate. ''Plos Biology'', ''3''(10), e314. doi: 10.1371/journal.pbio.0030314</ref> This poses significant limitations on findings derived from killifishes.
	*Each killifish requires approximately 1 liter of water.<ref>Dodzian, J., Kean, S., Seidel, J., & Valenzano, D. (2018). A Protocol for Laboratory Housing of Turquoise Killifish (&lt;em&gt;Nothobranchius furzeri&lt;/em&gt;). ''Journal Of Visualized Experiments'', (134). doi: 10.3791/57073</ref> This aspect becomes very troublesome for high throughput assays when taking into account space logistics. Furthermore, it ~~can~~ even prohibit pharmacological approaches, given that incredibly large amounts of drugs would need to be diluted in 1L of water to potentially have an effect.		*Each killifish requires approximately 1 liter of water.<ref>Dodzian, J., Kean, S., Seidel, J., & Valenzano, D. (2018). A Protocol for Laboratory Housing of Turquoise Killifish (&lt;em&gt;Nothobranchius furzeri&lt;/em&gt;). ''Journal Of Visualized Experiments'', (134). doi: 10.3791/57073</ref> This aspect becomes very troublesome for high throughput assays when taking into account space logistics. Furthermore, it may even prohibit pharmacological approaches, given that incredibly large amounts of drugs would need to be diluted in 1L of water to potentially have an effect.

	==References==		==References==