Print Email Facebook Twitter Transcriptional profiling of human familial longevity indicates a role for ASF1A and IL7R Title Transcriptional profiling of human familial longevity indicates a role for ASF1A and IL7R Author Passtoors, W.M. Boer, J.M. Goeman, J.G. Van den Akker, E.B. Deelen, J. Zwaan, B.J. Scarborough, A. Van der Breggen, R. Vossen, R.H.A.M. Faculty Electrical Engineering, Mathematics and Computer Science Department Intelligent Systems Date 2012-01-11 Abstract The Leiden Longevity Study consists of families that express extended survival across generations, decreased morbidity in middle-age, and beneficial metabolic profiles. To identify which pathways drive this complex phenotype of familial longevity and healthy aging, we performed a genome-wide gene expression study within this cohort to screen for mRNAs whose expression changes with age and associates with longevity. We first compared gene expression profiles from whole blood samples between 50 nonagenarians and 50 middle-aged controls, resulting in identification of 2,953 probes that associated with age. Next, we determined which of these probes associated with longevity by comparing the offspring of the nonagenarians (50 subjects) and the middle-aged controls. The expression of 360 probes was found to change differentially with age in members of the long-lived families. In a RT-qPCR replication experiment utilizing 312 controls, 332 offspring and 79 nonagenarians, we confirmed a nonagenarian specific expression profile for 21 genes out of 25 tested. Since only some of the offspring will have inherited the beneficial longevity profile from their long-lived parents, the contrast between offspring and controls is expected to be weak. Despite this dilution of the longevity effects, reduced expression levels of two genes, ASF1A and IL7R, involved in maintenance of chromatin structure and the immune system, associated with familial longevity already in middle-age. The size of this association increased when controls were compared to a subfraction of the offspring that had the highest probability to age healthily and become long-lived according to beneficial metabolic parameters. In conclusion, an ‘‘aging-signature’’ formed of 21 genes was identified, of which reduced expression of ASF1A and IL7R marked familial longevity already in middle-age. This indicates that expression changes of genes involved in metabolism, epigenetic control and immune function occur as a function of age, and some of these, like ASF1A and IL7R, represent early features of familial longevity and healthy ageing. To reference this document use: http://resolver.tudelft.nl/uuid:2f16b348-81e2-43b3-aaf1-ebd957cdc335 DOI https://doi.org/10.1371/journal.pone.0027759 Publisher Public Library of Science ISSN 1932-6203 Source http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027759 Source Plos One, 7 (1), 2012 Part of collection Institutional Repository Document type journal article Rights © 2012 Passtoors et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Files PDF journal.pone.0027759.pdf 2.16 MB Close viewer /islandora/object/uuid:2f16b348-81e2-43b3-aaf1-ebd957cdc335/datastream/OBJ/view