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A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila

Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the dec2 gene (dec2(P384R)) present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the dec2(P384R)...

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Autores principales: Pandey, Pritika, Wall, P. Kerr, Lopez, Stephen R., Dubuisson, Olga S., Zunica, Elizabeth R.M., Dantas, Wagner S., Kirwan, John P., Axelrod, Christopher L., Johnson, Alyssa E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312989/
https://www.ncbi.nlm.nih.gov/pubmed/37398097
http://dx.doi.org/10.21203/rs.3.rs-2882949/v1
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author Pandey, Pritika
Wall, P. Kerr
Lopez, Stephen R.
Dubuisson, Olga S.
Zunica, Elizabeth R.M.
Dantas, Wagner S.
Kirwan, John P.
Axelrod, Christopher L.
Johnson, Alyssa E.
author_facet Pandey, Pritika
Wall, P. Kerr
Lopez, Stephen R.
Dubuisson, Olga S.
Zunica, Elizabeth R.M.
Dantas, Wagner S.
Kirwan, John P.
Axelrod, Christopher L.
Johnson, Alyssa E.
author_sort Pandey, Pritika
collection PubMed
description Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the dec2 gene (dec2(P384R)) present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the dec2(P384R) mutation activates compensatory mechanisms that allows these individuals to thrive with less sleep. To test this directly, we used a Drosophila model to study the effects of the dec2(P384R) mutation on animal health. Expression of human dec2(P384R) in fly sleep neurons was sufficient to mimic the short sleep phenotype and, remarkably, dec2(P384R) mutants lived significantly longer with improved health despite sleeping less. The improved physiological effects were enabled, in part, by enhanced mitochondrial fitness and upregulation of multiple stress response pathways. Moreover, we provide evidence that upregulation of pro-health pathways also contributes to the short sleep phenotype, and this phenomenon may extend to other pro-longevity models.
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spelling pubmed-103129892023-07-01 A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila Pandey, Pritika Wall, P. Kerr Lopez, Stephen R. Dubuisson, Olga S. Zunica, Elizabeth R.M. Dantas, Wagner S. Kirwan, John P. Axelrod, Christopher L. Johnson, Alyssa E. Res Sq Article Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the dec2 gene (dec2(P384R)) present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the dec2(P384R) mutation activates compensatory mechanisms that allows these individuals to thrive with less sleep. To test this directly, we used a Drosophila model to study the effects of the dec2(P384R) mutation on animal health. Expression of human dec2(P384R) in fly sleep neurons was sufficient to mimic the short sleep phenotype and, remarkably, dec2(P384R) mutants lived significantly longer with improved health despite sleeping less. The improved physiological effects were enabled, in part, by enhanced mitochondrial fitness and upregulation of multiple stress response pathways. Moreover, we provide evidence that upregulation of pro-health pathways also contributes to the short sleep phenotype, and this phenomenon may extend to other pro-longevity models. American Journal Experts 2023-06-02 /pmc/articles/PMC10312989/ /pubmed/37398097 http://dx.doi.org/10.21203/rs.3.rs-2882949/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Pandey, Pritika
Wall, P. Kerr
Lopez, Stephen R.
Dubuisson, Olga S.
Zunica, Elizabeth R.M.
Dantas, Wagner S.
Kirwan, John P.
Axelrod, Christopher L.
Johnson, Alyssa E.
A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila
title A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila
title_full A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila
title_fullStr A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila
title_full_unstemmed A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila
title_short A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila
title_sort familial natural short sleep mutation promotes healthy aging and extends lifespan in drosophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312989/
https://www.ncbi.nlm.nih.gov/pubmed/37398097
http://dx.doi.org/10.21203/rs.3.rs-2882949/v1
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