Replicative senescence is associated with nuclear reorganization and with DNA methylation at specific transcription factor binding sites.

Subsequently, we performed gene ontology (GO) analysis of differentially expressed genes to gain better insight in the functional changes during long-term culture: downregulated genes revealed a highly significant enrichment in categories involved in cell division and DNA repair whereas upregulated genes were enriched in cell adhesion, development, and extracellular matrix organization (Figure 4 E).

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