Genomic and Epigenomic Alterations (A) Genomic instability and telomere attrition. Endogenous or exogenous agents can stimulate a variety of DNA lesions that are schematically represented on one single chromosome. Such lesions can be repaired by a variety of mechanisms. Excessive DNA damage or insufficient DNA repair favors the aging process. Note that both nuclear DNA and mitochondrial DNA (not represented here) are subjected to age-associated genomic alterations. BER, base excision repair; HR, homologous recombination; NER, nucleotide excision repair; NHEJ, nonhomologous end-joining; MMR, mismatch repair; ROS, reactive oxygen species; TLS, translesion synthesis; SAC, spindle assembly checkpoint (Vijg, 2007). (B) Epigenetic alterations. Alterations in the methylation of DNA or acetylation and methylation of histones, as well as of other chromatin-associated proteins, can induce epigenetic changes that contribute to the aging process.