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Immunity and Ageing

, 12:21

First Online: 11 November 2015Received: 07 September 2015Accepted: 29 October 2015

Abstract

BackgroundThe 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.

ResultsWe observed that expression levels within the IL7R gene network were significantly different between the nonagenarians and middle-aged controls P = 4.6 × 10, 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.

ConclusionsOverall, 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.

KeywordsIL7R Gene expression Healthy ageing Electronic supplementary materialThe online version of this article doi:10.1186-s12979-015-0048-6 contains supplementary material, which is available to authorized users.

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Autor: Willemijn M. Passtoors - Erik B. van den Akker - Joris Deelen - Andrea B. Maier - Ruud van der Breggen - Rick Jansen - St

Fuente: https://link.springer.com/







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