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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.

IL7R gene expression network associates with human healthy ageing