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

Nadine Saul, Ineke Dhondt (UGent) , Mikko Kuokkanen, Markus Perola, Clara Verschuuren (UGent) , Brecht Wouters, Henrik von Chrzanowski, Winnok H. De Vos, Liesbet Temmerman, Walter Luyten, et al.
(2022) BIOGERONTOLOGY. 23(4). p.431-452
Author
Organization
Project
  • Ageing with elegans (Validating C. elegans healthspan model for better understanding factors causing health disease, to develop evidence based prevention, diagnostic)
Abstract
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.
Keywords
Geriatrics and Gerontology, Gerontology, Aging, Healthspan, Ageing, GWAS, C, elegans, Muscle integrity, Stress resistance, YES-ASSOCIATED PROTEIN, C.-ELEGANS, LIFE-SPAN, CELL-PROLIFERATION, SENSORY PERCEPTION, STRESS, PATHWAY, IMMUNOSENESCENCE, INFLAMMATION, INTEGRATION

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Citation

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MLA
Saul, Nadine, et al. “Identification of Healthspan-Promoting Genes in Caenorhabditis Elegans Based on a Human GWAS Study.” BIOGERONTOLOGY, vol. 23, no. 4, 2022, pp. 431–52, doi:10.1007/s10522-022-09969-8.
APA
Saul, N., Dhondt, I., Kuokkanen, M., Perola, M., Verschuuren, C., Wouters, B., … Braeckman, B. (2022). Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study. BIOGERONTOLOGY, 23(4), 431–452. https://doi.org/10.1007/s10522-022-09969-8
Chicago author-date
Saul, Nadine, Ineke Dhondt, Mikko Kuokkanen, Markus Perola, Clara Verschuuren, Brecht Wouters, Henrik von Chrzanowski, et al. 2022. “Identification of Healthspan-Promoting Genes in Caenorhabditis Elegans Based on a Human GWAS Study.” BIOGERONTOLOGY 23 (4): 431–52. https://doi.org/10.1007/s10522-022-09969-8.
Chicago author-date (all authors)
Saul, Nadine, Ineke Dhondt, Mikko Kuokkanen, Markus Perola, Clara Verschuuren, Brecht Wouters, Henrik von Chrzanowski, Winnok H. De Vos, Liesbet Temmerman, Walter Luyten, Aleksandra Zečić, Tim Loier, Christian Schmitz-Linneweber, and Bart Braeckman. 2022. “Identification of Healthspan-Promoting Genes in Caenorhabditis Elegans Based on a Human GWAS Study.” BIOGERONTOLOGY 23 (4): 431–452. doi:10.1007/s10522-022-09969-8.
Vancouver
1.
Saul N, Dhondt I, Kuokkanen M, Perola M, Verschuuren C, Wouters B, et al. Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study. BIOGERONTOLOGY. 2022;23(4):431–52.
IEEE
[1]
N. Saul et al., “Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study,” BIOGERONTOLOGY, vol. 23, no. 4, pp. 431–452, 2022.
@article{8758743,
  abstract     = {{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.}},
  author       = {{Saul, Nadine and Dhondt, Ineke and Kuokkanen, Mikko and Perola, Markus and Verschuuren, Clara and Wouters, Brecht and von Chrzanowski, Henrik and De Vos, Winnok H. and Temmerman, Liesbet and Luyten, Walter and Zečić, Aleksandra and Loier, Tim and Schmitz-Linneweber, Christian and Braeckman, Bart}},
  issn         = {{1389-5729}},
  journal      = {{BIOGERONTOLOGY}},
  keywords     = {{Geriatrics and Gerontology,Gerontology,Aging,Healthspan,Ageing,GWAS,C,elegans,Muscle integrity,Stress resistance,YES-ASSOCIATED PROTEIN,C.-ELEGANS,LIFE-SPAN,CELL-PROLIFERATION,SENSORY PERCEPTION,STRESS,PATHWAY,IMMUNOSENESCENCE,INFLAMMATION,INTEGRATION}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{431--452}},
  title        = {{Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study}},
  url          = {{http://dx.doi.org/10.1007/s10522-022-09969-8}},
  volume       = {{23}},
  year         = {{2022}},
}
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