Schematic overview of how SA-DNAm changes may influence cellular senescence. Senescence is associated with a continuous gain of SA-DNAm changes that are enriched in genes with repressive histone marks. They may be associated with permanent gene silencing, but this link is yet unproven and therefore labeled with a question mark. SA-DNAm changes are not affected by ionizing radiation or telomere length. However, these processes evoke chromosomal aberrations and may ultimately activate the same downstream signal cascades of cellular senescence (including activation of CDKN1A, CDKN2A, and TP53). Pluripotent cells hardly reveal SA-DNAm changes; avoidance from these epigenetic modifications might contribute to the escape of pluripotent cells from cellular senescence.
