Cargando…

Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study

To find drivers of healthy ageing, a genome-wide association study (GWAS) was performed in healthy and unhealthy older individuals. Healthy individuals were defined as free from cardiovascular disease, stroke, heart failure, major adverse cardiovascular event, diabetes, dementia, cancer, chronic obs...

Descripción completa

Detalles Bibliográficos
Autores principales: Saul, Nadine, Dhondt, Ineke, Kuokkanen, Mikko, Perola, Markus, Verschuuren, Clara, Wouters, Brecht, von Chrzanowski, Henrik, De Vos, Winnok H., Temmerman, Liesbet, Luyten, Walter, Zečić, Aleksandra, Loier, Tim, Schmitz-Linneweber, Christian, Braeckman, Bart P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388463/
https://www.ncbi.nlm.nih.gov/pubmed/35748965
http://dx.doi.org/10.1007/s10522-022-09969-8
_version_ 1784770231421370368
author Saul, Nadine
Dhondt, Ineke
Kuokkanen, Mikko
Perola, Markus
Verschuuren, Clara
Wouters, Brecht
von Chrzanowski, Henrik
De Vos, Winnok H.
Temmerman, Liesbet
Luyten, Walter
Zečić, Aleksandra
Loier, Tim
Schmitz-Linneweber, Christian
Braeckman, Bart P.
author_facet Saul, Nadine
Dhondt, Ineke
Kuokkanen, Mikko
Perola, Markus
Verschuuren, Clara
Wouters, Brecht
von Chrzanowski, Henrik
De Vos, Winnok H.
Temmerman, Liesbet
Luyten, Walter
Zečić, Aleksandra
Loier, Tim
Schmitz-Linneweber, Christian
Braeckman, Bart P.
author_sort Saul, Nadine
collection PubMed
description To find drivers of healthy ageing, a genome-wide association study (GWAS) was performed in healthy and unhealthy older individuals. Healthy individuals were defined as free from cardiovascular disease, stroke, heart failure, major adverse cardiovascular event, diabetes, dementia, cancer, chronic obstructive pulmonary disease (COPD), asthma, rheumatism, Crohn’s disease, malabsorption or kidney disease. Six single nucleotide polymorphisms (SNPs) with unknown function associated with ten human genes were identified as candidate healthspan markers. Thirteen homologous or closely related genes were selected in the model organism C. elegans for evaluating healthspan after targeted RNAi-mediated knockdown using pathogen resistance, muscle integrity, chemotaxis index and the activity of known longevity and stress response pathways as healthspan reporters. In addition, lifespan was monitored in the RNAi-treated nematodes. RNAi knockdown of yap-1, wwp-1, paxt-1 and several acdh genes resulted in heterogeneous phenotypes regarding muscle integrity, pathogen resistance, chemotactic behaviour, and lifespan. Based on these observations, we hypothesize that their human homologues WWC2, CDKN2AIP and ACADS may play a role in health maintenance in the elderly. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10522-022-09969-8.
format Online
Article
Text
id pubmed-9388463
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Springer Netherlands
record_format MEDLINE/PubMed
spelling pubmed-93884632022-08-20 Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study Saul, Nadine Dhondt, Ineke Kuokkanen, Mikko Perola, Markus Verschuuren, Clara Wouters, Brecht von Chrzanowski, Henrik De Vos, Winnok H. Temmerman, Liesbet Luyten, Walter Zečić, Aleksandra Loier, Tim Schmitz-Linneweber, Christian Braeckman, Bart P. Biogerontology Research Article To find drivers of healthy ageing, a genome-wide association study (GWAS) was performed in healthy and unhealthy older individuals. Healthy individuals were defined as free from cardiovascular disease, stroke, heart failure, major adverse cardiovascular event, diabetes, dementia, cancer, chronic obstructive pulmonary disease (COPD), asthma, rheumatism, Crohn’s disease, malabsorption or kidney disease. Six single nucleotide polymorphisms (SNPs) with unknown function associated with ten human genes were identified as candidate healthspan markers. Thirteen homologous or closely related genes were selected in the model organism C. elegans for evaluating healthspan after targeted RNAi-mediated knockdown using pathogen resistance, muscle integrity, chemotaxis index and the activity of known longevity and stress response pathways as healthspan reporters. In addition, lifespan was monitored in the RNAi-treated nematodes. RNAi knockdown of yap-1, wwp-1, paxt-1 and several acdh genes resulted in heterogeneous phenotypes regarding muscle integrity, pathogen resistance, chemotactic behaviour, and lifespan. Based on these observations, we hypothesize that their human homologues WWC2, CDKN2AIP and ACADS may play a role in health maintenance in the elderly. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10522-022-09969-8. Springer Netherlands 2022-06-24 2022 /pmc/articles/PMC9388463/ /pubmed/35748965 http://dx.doi.org/10.1007/s10522-022-09969-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Saul, Nadine
Dhondt, Ineke
Kuokkanen, Mikko
Perola, Markus
Verschuuren, Clara
Wouters, Brecht
von Chrzanowski, Henrik
De Vos, Winnok H.
Temmerman, Liesbet
Luyten, Walter
Zečić, Aleksandra
Loier, Tim
Schmitz-Linneweber, Christian
Braeckman, Bart P.
Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study
title Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study
title_full Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study
title_fullStr Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study
title_full_unstemmed Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study
title_short Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study
title_sort identification of healthspan-promoting genes in caenorhabditis elegans based on a human gwas study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388463/
https://www.ncbi.nlm.nih.gov/pubmed/35748965
http://dx.doi.org/10.1007/s10522-022-09969-8
work_keys_str_mv AT saulnadine identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT dhondtineke identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT kuokkanenmikko identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT perolamarkus identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT verschuurenclara identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT woutersbrecht identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT vonchrzanowskihenrik identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT devoswinnokh identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT temmermanliesbet identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT luytenwalter identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT zecicaleksandra identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT loiertim identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT schmitzlinneweberchristian identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy
AT braeckmanbartp identificationofhealthspanpromotinggenesincaenorhabditiselegansbasedonahumangwasstudy