PMID- 26566388 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20151114 LR - 20200930 IS - 1742-4933 (Print) IS - 1742-4933 (Electronic) IS - 1742-4933 (Linking) VI - 12 DP - 2015 TI - IL7R gene expression network associates with human healthy ageing. PG - 21 LID - 10.1186/s12979-015-0048-6 [doi] LID - 21 AB - 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 x 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 x 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. FAU - Passtoors, Willemijn M AU - Passtoors WM AD - Section of Molecular Epidemiology, Leiden University Medical Center, Zone S5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. FAU - van den Akker, Erik B AU - van den Akker EB AD - Section of Molecular Epidemiology, Leiden University Medical Center, Zone S5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands ; The Delft Bioinformatics Lab, Delft University of Technology, 2600 GA Delft, The Netherlands. FAU - Deelen, Joris AU - Deelen J AD - Section of Molecular Epidemiology, Leiden University Medical Center, Zone S5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands ; Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. FAU - Maier, Andrea B AU - Maier AB AD - Section of Gerontology and Geriatrics, Department of Internal Medicine, VU University Medical Center, Amsterdam, Netherlands. FAU - van der Breggen, Ruud AU - van der Breggen R AD - Section of Molecular Epidemiology, Leiden University Medical Center, Zone S5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. FAU - Jansen, Rick AU - Jansen R AD - Department of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, 1081 BT Amsterdam, The Netherlands. FAU - Trompet, Stella AU - Trompet S AD - Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands ; Department of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. FAU - van Heemst, Diana AU - van Heemst D AD - Department of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. FAU - Derhovanessian, Evelyna AU - Derhovanessian E AD - Center for Medical Research, University of Tubingen, 72072 Tubingen, Germany. FAU - Pawelec, Graham AU - Pawelec G AD - Center for Medical Research, University of Tubingen, 72072 Tubingen, Germany. FAU - van Ommen, Gert-Jan B AU - van Ommen GJ AD - Center for Human and Clinical Genetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands ; The Netherlands Center for Medical Systems Biology, Leiden, The Netherlands. FAU - Slagboom, P Eline AU - Slagboom PE AD - Section of Molecular Epidemiology, Leiden University Medical Center, Zone S5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands ; Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. FAU - Beekman, Marian AU - Beekman M AD - Section of Molecular Epidemiology, Leiden University Medical Center, Zone S5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands ; Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. LA - eng PT - Journal Article DEP - 20151111 PL - England TA - Immun Ageing JT - Immunity & ageing : I & A JID - 101235427 PMC - PMC4642670 OTO - NOTNLM OT - Gene expression OT - Healthy ageing OT - IL7R EDAT- 2015/11/14 06:00 MHDA- 2015/11/14 06:01 PMCR- 2015/11/11 CRDT- 2015/11/14 06:00 PHST- 2015/09/07 00:00 [received] PHST- 2015/10/29 00:00 [accepted] PHST- 2015/11/14 06:00 [entrez] PHST- 2015/11/14 06:00 [pubmed] PHST- 2015/11/14 06:01 [medline] PHST- 2015/11/11 00:00 [pmc-release] AID - 48 [pii] AID - 10.1186/s12979-015-0048-6 [doi] PST - epublish SO - Immun Ageing. 2015 Nov 11;12:21. doi: 10.1186/s12979-015-0048-6. eCollection 2015.