Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing

Lorna W. Harries, Dena Hernandez, William Henley, Andrew R. Wood, Alice C. Holly, Rachel M. Bradley-Smith, Hanieh Yaghootkar, Ambarish Dutta, Anna Murray, Timothy M. Frayling, Jack M. Guralnik, Stefania Bandinelli, Andrew Singleton, Luigi Ferrucci, David Melzer

Research output: Contribution to journalArticle

Abstract

Summary: 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 30-104years). 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 16571 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

Original languageEnglish (US)
Pages (from-to)868-878
Number of pages11
JournalAging Cell
Volume10
Issue number5
DOIs
StatePublished - Oct 2011
Externally publishedYes

Keywords

  • Aging
  • Cell senescence
  • Gene expression
  • MRNA processing
  • Predictive model

ASJC Scopus subject areas

  • Cell Biology
  • Aging

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    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., & Melzer, D. (2011). Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing. Aging Cell, 10(5), 868-878. https://doi.org/10.1111/j.1474-9726.2011.00726.x