Chip-chip and MIRA-chip from primary skin fibroblasts, derived of matched pairs of early and late donor age. Homo sapiens

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: H3K4me3, H3K27me3 and DNA- methylation longitudinal aging profiles from primary skin fibroblasts from matched pairs of early (E) and late (L) stages in life.