The presence of DNA damage and subsequent up-regulation of p16(INK4a) in quiescent cells in vivo may induce a pre-senescent state that converts to a full senescent state when cells are stimulated to proliferate. This suggests that DNA replication is required to induce a persistent DDR associated with cell senescence. For example, damage to skeletal muscle in normal young mice causes the activation of quiescent satellite cells (adult stem cells), which proliferate and undergo myogenic differentiation required for muscle repair. However, a recent study has shown that in geriatric mice (28-32 months of age), satellite cell activation is impaired and satellite cells instead convert from a pre-senescent state (quiescent cells with high p16(INK4a) expression) to a full senescent state (including a DDR) when stimulated to proliferate in response to injury. As such, the induction of senescent satellite cells with age can impair satellite muscle regeneration. This study suggests that senescent cells may accumulate in late life due to a conversion from quiescence to senescence (termed geroconversion) in response to a requirement for cells to replicate over time to regenerate tissue. In this model, more and more quiescent cells are likely to accumulate DNA damage over the life-time of an organism and are therefore more likely to become senescent when induced to proliferate later in life. Therefore, if quiescent cells inflicted with DNA damage convert to senescence when stimulated to proliferate, then eliminating such damage may prevent this conversion.