DNA damage and repair

From Longevity Wiki

DNA damage is comprised in genomic instability as one of the hallmarks of aging.[1][2] Genome instability is associated to aging across species, from multicellular organisms to prokaryotes,[3] and it refers to the high occurrence of DNA damage or mutations within the genome. Some researchers argue that DNA damage is the causal driver of aging, and it is regarded as one of the main theories of aging.

The genome is constantly exposed to both sources of endogenous DNA damage (such as the generation of toxic o deleterious metabolites arising from metabolic pathways, or stochastic processes), as well as to exogenous sources of DNA damage (such as exposure to UV radiation or mutagens). While DNA repair mechanisms exist that counteract these events, they are not able to fully remove all damage, and repair mechanisms themselves are subject to deteriorative processes.

DNA damage

Endogenous DNA damage


Single-Stranded Breaks (SSBs)

Double-Stranded Breaks (DSBs)

Base hydrolysis

Base modifications

Exogenous DNA damage

UV radiation

DNA repair

Nucleotide excision repair (NER)

Base excision repair (BER)

DNA double-strand break repair

  1. López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
  2. López-Otín, C. et al. (2023) “Hallmarks of aging: An expanding universe,” Cell, 186(2), pp. 243–278. Available at: https://doi.org/10.1016/j.cell.2022.11.001.
  3. Darmon, E., & Leach, D. R. (2014). Bacterial genome instability. Microbiology and Molecular Biology Reviews, 78(1), 1-39.