Figure 4.

The crosstalk between epigenetic changes, transcription, and genomic instability. In a young organism, transcription is fully controlled and produced the same amount of mRNA in the cells that activate the same genes. In these cells, normal chromatin state and genomic stability are maintained. With increased age, genomic instability increases, resulting in gene mutations and chromosomal aberrations and unstable transcription. Increased DNA damage may result in DNA damage response inducing the recruitment of epigenetic modifiers of chromatin structure and locally resuming its conformation, which may partly stabilize the transcription of neighboring genes. Epimutations, which accumulate in later life, may hamper this process.