These authors contributed equally to this publication.
Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing
Article first published online: 19 JUL 2011
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland
Volume 10, Issue 5, pages 868–878, October 2011
How to Cite
Harries, L. W., Hernandez, D., Henley, W., Wood, A. R., Holly, A. C., Bradley-Smith, R. M., Yaghootkar, H., Dutta, A., Murray, A., Frayling, T. M., Guralnik, J. M., Bandinelli, S., Singleton, A., Ferrucci, L. and Melzer, D. (2011), Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing. Aging Cell, 10: 868–878. doi: 10.1111/j.1474-9726.2011.00726.x
- Issue published online: 14 SEP 2011
- Article first published online: 19 JUL 2011
- Accepted manuscript online: 13 JUN 2011 01:40AM EST
- Accepted for publication 31 May 2011
- cell senescence;
- mRNA processing;
- gene expression;
- predictive model
Aging is a major risk factor for chronic disease in the human population, but there are little human data on gene expression alterations that accompany the process. We examined human peripheral blood leukocyte in-vivo RNA in a large-scale transcriptomic microarray study (subjects aged 30–104 years). We tested associations between probe expression intensity and advancing age (adjusting for confounding factors), initially in a discovery set (n = 458), following-up findings in a replication set (n = 240). We confirmed expression of key results by real-time PCR. Of 16 571 expressed probes, only 295 (2%) were robustly associated with age. Just six probes were required for a highly efficient model for distinguishing between young and old (area under the curve in replication set; 95%). The focused nature of age-related gene expression may therefore provide potential biomarkers of aging. Similarly, only 7 of 1065 biological or metabolic pathways were age-associated, in gene set enrichment analysis, notably including the processing of messenger RNAs (mRNAs); [P < 0.002, false discovery rate (FDR) q < 0.05]. This is supported by our observation of age-associated disruption to the balance of alternatively expressed isoforms for selected genes, suggesting that modification of mRNA processing may be a feature of human aging.