Unknown,Transcriptomics,Genomics,Proteomics

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RNA-seq from primary skin fibroblasts, derived of matched pairs of middle and late donor age


ABSTRACT: Aging signatures developed from a longitudinal study design are dominated by reduced transcription of genes involved in protein synthesis Aging is a multifactorial process where the impact of singular components still remains unclear. Furthermore, previous studies were focused on measuring specific traits such as DNA -methylation and used categorical group-wise designs, unable to capture intra-individual signature changes. Here we have developed a new method for a longitudinal, age-related analysis combining the merits of a pair-wise design with the statistical power of gene set enrichment analysis. We present an integrated analysis, including transcriptional changes and genome-wide epigenetic changes in DNA- methylation, H3K4- and H3K27- histone methylation in promoter regions. We tested our method on a rare collection of paired skin fibroblast samples from male middle age to old age transitions and obtained functional, age-related clusters. By using a set of only ten individuals, we could demonstrate a high overlap of functional terms to previously established tissue-independent age signatures including extracellular matrix, apoptosis and oxidative stress. Importantly, we identify protein translation-related processes as the main cluster of age-driven, specific down regulation. Evaluation of transcriptional changes in matched sample pairs of primary skin fibroblasts from middle and old age.

ORGANISM(S): Homo sapiens

SUBMITTER: Marc Jung 

PROVIDER: E-GEOD-51518 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Jung Marc M   Jin Seung-Gi SG   Zhang Xiaoying X   Xiong Wenying W   Gogoshin Grigoriy G   Rodin Andrei S AS   Pfeifer Gerd P GP  

Nucleic acids research 20150514 15


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 n  ...[more]

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