**2. Age-related changes in DNA repair**

 Each day, the integrity and stability of DNA are challenged by exogenous physical, chemical, or biological agents, as well as by endogenous processes, including DNA replication mistakes, spontaneous hydrolytic reactions, and reactive oxygen species (ROS). Thus, depending on the source of damage, DNA can be affected in different ways, including nucleotide alterations, bulky adducts, single-strand breaks (SSB), and double-strand breaks (DSB). To combat threats posed by DNA damage, cells have evolved complex and finely regulated mechanisms collectively referred to as DNA damage response (DDR) which detects DNA lesions, signals their presence, and promotes their repair [22–24]. However, according with the genome maintenance hypothesis of aging, DNA repair can itself be subject to age-related changes and deterioration, allowing accumulation of damages (**Figure 2**). The wide diversity of DNA-lesion types requires multiple, largely distinct DNA repair mechanisms that differ in their components, whereas some lesions are subject to direct protein-mediated reversal, most are repaired by a sequence of catalytic events mediated by multiple proteins [22]. Thus, cells with defects in key proteins involved in DDR have been shown an accelerated aging phenotype caused by the accumulation of mutations and epimutations that eventually cause malfunction of the cells, senescence, or apoptosis [25].
