Top Highlights

• DNA damage that is not repaired in a timely manner or is too egregious to be repaired induces signaling events that lead to one of many cell fates, one of which, senescence, plays a causal role in aging
• Maintaining genome stability is a continuous process
• DNA damage is a constant threat because nucleic acids are chemically unstable under physiological conditions and vulnerable to attack by endogenous and environmental factors
• DNA is also vulnerable to chemical attack by electrophiles and free radicals. While exogenous sources of genotoxic stress can be quite potent, endogenous threats are constant and relentless
• This suggests that aging might be driven by many types of cellular damage yet does not occur until one reaches a state where multiple aspects of cell biology are perturbed, for example, genome integrity, proteostasis, and mitochondrial function.

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