About this Research Topic
Activation of the DNA damage response (DDR) is critical for preventing cancer; however, chronic activation of the DDR is thought to drive the accumulation of senescent cells and chronic sterile inflammation in old age. As an example, ROS plays an important role in the aging process by causing oxidative damage to biomolecules in cells. ROS can cause either DNA single-strand base oxidative modification, single-strand nicks, or double-strand breaks (DSBs). A subset of single-strand nicks may be converted to DSBs if they persist in being present during DNA replication. After recognition of DNA damage, nicks or breaks can be repaired by nucleotide excision repair (NER), base excision repair (BER), or non-homologous end-joining (NHEJ). If replication forks or transcription complexes encounter polymerase-blocking lesions, that can lead to the formation of a DSB or R-loop. After that, a signaling cascade is initiated to halt cell cycle progression and promote repair. Irreparable damage signals that avoid replicating a damaged genome, and mutagenesis selects the fate by activating events that lead to cell death or irreversible cell cycle arrest.
Senescence or aging causes a permanent arrest in proliferation in response to various stresses. No single mechanism or pathway fully accounts for age-associated functional decline. It has not been proven, but studies suggest that DNA damage is the most potent cause of aging. In most premature aging or progeroid-like syndromes, mutations are found in genes involved in maintaining genome stability. Defects in DSB repair result in progeroid conditions such as ataxia-telangiectasia and Nijmegen breakage syndrome, and DNA crosslink-repair deficiencies cause Fanconi anemia.
The goal of this Research Topic is to address the biological rationale of the aging process on the basis of macromolecular damage. New strategies can be designed, and the current knowledge can be implemented that may prevent or delay cellular senescence. The retrospective review of the downstream consequences of DNA damage will help to find the gap between the epidemiological findings and their underlying biological mechanisms. As the field still lacks tools to quantify the DNA lesions and capacity of DNA repair, this limits the researchers to understand the linkage between this critical cellular process and drivers of aging. This Research Topic will improve and enrich the area to help build such a tool kit that would enable a more precise determination of dynamics of a DSB and chromatin composition within the nuclear space. It might open new opportunities in precision medicine, enabling the maintenance of genomic homeostasis, for example, improving tumor ablation, slowing the loss of irreplaceable cells, or optimizing metabolism to promote repair.
We welcome submissions from Reviews, Perspectives, and Comments that include (but are not limited to the following):
• Recent developments in the field of DNA repair, mutation, and aging research.
• Basic biology of DNA damage repair, mutation, senescence to clinical implications of stress-induced DNA damage.
• Translational research examining the connection between aging and disease in a variety of animal models.
• Clinical research focusing on aging-associated medical conditions, including age-related cancers, and medical and health research specifically focusing on older people.
Keywords: DNA Damage, DNA Repair, Mutation, Senescence, Aging
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.