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

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. Overall design: Evaluation of transcriptional changes in matched sample pairs of primary skin fibroblasts from middle and old age.

20

Jung M, Jin SG, Zhang X, Xiong W, Gogoshin G, Rodin AS, Pfeifer GP