Model for loss of silencing over time in aging. Sir2 is present at silenced chromatin and can be recruited to sites of DNA damage, which occurs chronically over a lifetime. Damage may be induced during DNA replication in dividing cells, and may be exacerbated by mutations in DNA repair functions, such as the Werner DNA helicase. ROS, especially in nondividing cells, may also contribute to DNA damage. If the resetting of silenced chromatin were <100% efficient, there would be a gradual erosion of silencing, which may lead to inappropriate gene expression or genome instability.