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Nucleic Acids Res. 2015 Sep 3;43(15):e100. doi: 10.1093/nar/gkv473. Epub 2015 May 14.

Longitudinal epigenetic and gene expression profiles analyzed by three-component analysis reveal down-regulation of genes involved in protein translation in human aging.

Author information

1
Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA mjung@illumina.com.
2
Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
3
Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
4
Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
5
Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA arodin@coh.org.
6
Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA gerd.pfeifer@vai.org.

Abstract

Data on biological mechanisms of aging are mostly obtained from cross-sectional study designs. An inherent disadvantage of this design is that inter-individual differences can mask small but biologically significant age-dependent changes. A serially sampled design (same individual at different time points) would overcome this problem but is often limited by the relatively small numbers of available paired samples and the statistics being used. To overcome these limitations, we have developed a new vector-based approach, termed three-component analysis, which incorporates temporal distance, signal intensity and variance into one single score for gene ranking and is combined with gene set enrichment analysis. We tested our method on a unique age-based sample set of human skin fibroblasts and combined genome-wide transcription, DNA methylation and histone methylation (H3K4me3 and H3K27me3) data. Importantly, our method can now for the first time demonstrate a clear age-dependent decrease in expression of genes coding for proteins involved in translation and ribosome function. Using analogies with data from lower organisms, we propose a model where age-dependent down-regulation of protein translation-related components contributes to extend human lifespan.

PMID:
25977295
PMCID:
PMC4551908
DOI:
10.1093/nar/gkv473
[Indexed for MEDLINE]
Free PMC Article

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