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IL7R gene expression network associates with human healthy ageing
BACKGROUND: The level of expression of the interleukin 7 receptor (IL7R) gene in blood has recently been found to be associated with familial longevity and healthy ageing. IL7R is crucial for T cell development and important for immune competence. To further investigate the IL7R pathway in ageing, w...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642670/ https://www.ncbi.nlm.nih.gov/pubmed/26566388 http://dx.doi.org/10.1186/s12979-015-0048-6 |
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author | Passtoors, Willemijn M. van den Akker, Erik B. Deelen, Joris Maier, Andrea B. van der Breggen, Ruud Jansen, Rick Trompet, Stella van Heemst, Diana Derhovanessian, Evelyna Pawelec, Graham van Ommen, Gert-Jan B. Slagboom, P. Eline Beekman, Marian |
author_facet | Passtoors, Willemijn M. van den Akker, Erik B. Deelen, Joris Maier, Andrea B. van der Breggen, Ruud Jansen, Rick Trompet, Stella van Heemst, Diana Derhovanessian, Evelyna Pawelec, Graham van Ommen, Gert-Jan B. Slagboom, P. Eline Beekman, Marian |
author_sort | Passtoors, Willemijn M. |
collection | PubMed |
description | BACKGROUND: The level of expression of the interleukin 7 receptor (IL7R) gene in blood has recently been found to be associated with familial longevity and healthy ageing. IL7R is crucial for T cell development and important for immune competence. To further investigate the IL7R pathway in ageing, we identified the closest interacting genes to construct an IL7R gene network that consisted of IL7R and six interacting genes: IL2RG, IL7, TSLP, CRLF2, JAK1 and JAK3. This network was explored for association with chronological age, familial longevity and immune-related diseases (type 2 diabetes, chronic obstructive pulmonary disease and rheumatoid arthritis) in 87 nonagenarians, 337 of their middle-aged offspring and 321 middle-aged controls from the Leiden Longevity Study (LLS). RESULTS: We observed that expression levels within the IL7R gene network were significantly different between the nonagenarians and middle-aged controls (P = 4.6 × 10(−4)), being driven by significantly lower levels of expression in the elderly of IL7, IL2RG and IL7R. After adjustment for multiple testing and white blood cell composition and in comparison with similarly aged controls, middle-aged offspring of nonagenarian siblings exhibit a lower expression level of IL7R only (P = 0.006). Higher IL7R gene expression in the combined group of middle-aged offspring and controls is associated with a higher prevalence of immune-related disease (P = 0.001). On the one hand, our results indicate that lower IL7R expression levels, as exhibited by the members of long-lived families that can be considered as ‘healthy agers’, are beneficial in middle age. This is augmented by the observation that higher IL7R gene expression associates with immune-related disease. On the other hand, IL7R gene expression in blood is lower in older individuals, indicating that low IL7R gene expression might associate with reduced health. Interestingly, this contradictory result is supported by the observation that a higher IL7R gene expression level is associated with better prospective survival, both in the nonagenarians (Hazard ratio (HR) = 0.63, P = 0.037) and the middle-aged individuals (HR = 0.33, P = 1.9 × 10(–4)). CONCLUSIONS: Overall, we conclude that the IL7R network reflected by gene expression levels in blood may be involved in the rate of ageing and health status of elderly individuals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12979-015-0048-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4642670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46426702015-11-13 IL7R gene expression network associates with human healthy ageing Passtoors, Willemijn M. van den Akker, Erik B. Deelen, Joris Maier, Andrea B. van der Breggen, Ruud Jansen, Rick Trompet, Stella van Heemst, Diana Derhovanessian, Evelyna Pawelec, Graham van Ommen, Gert-Jan B. Slagboom, P. Eline Beekman, Marian Immun Ageing Research BACKGROUND: The level of expression of the interleukin 7 receptor (IL7R) gene in blood has recently been found to be associated with familial longevity and healthy ageing. IL7R is crucial for T cell development and important for immune competence. To further investigate the IL7R pathway in ageing, we identified the closest interacting genes to construct an IL7R gene network that consisted of IL7R and six interacting genes: IL2RG, IL7, TSLP, CRLF2, JAK1 and JAK3. This network was explored for association with chronological age, familial longevity and immune-related diseases (type 2 diabetes, chronic obstructive pulmonary disease and rheumatoid arthritis) in 87 nonagenarians, 337 of their middle-aged offspring and 321 middle-aged controls from the Leiden Longevity Study (LLS). RESULTS: We observed that expression levels within the IL7R gene network were significantly different between the nonagenarians and middle-aged controls (P = 4.6 × 10(−4)), being driven by significantly lower levels of expression in the elderly of IL7, IL2RG and IL7R. After adjustment for multiple testing and white blood cell composition and in comparison with similarly aged controls, middle-aged offspring of nonagenarian siblings exhibit a lower expression level of IL7R only (P = 0.006). Higher IL7R gene expression in the combined group of middle-aged offspring and controls is associated with a higher prevalence of immune-related disease (P = 0.001). On the one hand, our results indicate that lower IL7R expression levels, as exhibited by the members of long-lived families that can be considered as ‘healthy agers’, are beneficial in middle age. This is augmented by the observation that higher IL7R gene expression associates with immune-related disease. On the other hand, IL7R gene expression in blood is lower in older individuals, indicating that low IL7R gene expression might associate with reduced health. Interestingly, this contradictory result is supported by the observation that a higher IL7R gene expression level is associated with better prospective survival, both in the nonagenarians (Hazard ratio (HR) = 0.63, P = 0.037) and the middle-aged individuals (HR = 0.33, P = 1.9 × 10(–4)). CONCLUSIONS: Overall, we conclude that the IL7R network reflected by gene expression levels in blood may be involved in the rate of ageing and health status of elderly individuals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12979-015-0048-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-11 /pmc/articles/PMC4642670/ /pubmed/26566388 http://dx.doi.org/10.1186/s12979-015-0048-6 Text en © Passtoors et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Passtoors, Willemijn M. van den Akker, Erik B. Deelen, Joris Maier, Andrea B. van der Breggen, Ruud Jansen, Rick Trompet, Stella van Heemst, Diana Derhovanessian, Evelyna Pawelec, Graham van Ommen, Gert-Jan B. Slagboom, P. Eline Beekman, Marian IL7R gene expression network associates with human healthy ageing |
title | IL7R gene expression network associates with human healthy ageing |
title_full | IL7R gene expression network associates with human healthy ageing |
title_fullStr | IL7R gene expression network associates with human healthy ageing |
title_full_unstemmed | IL7R gene expression network associates with human healthy ageing |
title_short | IL7R gene expression network associates with human healthy ageing |
title_sort | il7r gene expression network associates with human healthy ageing |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642670/ https://www.ncbi.nlm.nih.gov/pubmed/26566388 http://dx.doi.org/10.1186/s12979-015-0048-6 |
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