-
Nature Aging Dec 2021Cellular metabolism generates molecular damage affecting all levels of biological organization. Accumulation of this damage over time is thought to play a central role... (Review)
Review
Cellular metabolism generates molecular damage affecting all levels of biological organization. Accumulation of this damage over time is thought to play a central role in the aging process, but damage manifests in diverse molecular forms complicating its assessment. Insufficient attention has been paid to date to the role of molecular damage in aging-related phenotypes, particularly in humans, in part because of the difficulty in measuring its various forms. Recently, omics approaches have been developed that begin to address this challenge, because they are able to assess a sizeable proportion of age-related damage at the level of small molecules, proteins, RNA, DNA, organelles and cells. This review describes the concept of molecular damage in aging and discusses its diverse aspects from theoretical models to experimental approaches. Measurement of multiple types of damage enables studies of the role of damage in human aging outcomes and lays a foundation for testing interventions to reduce the burden of molecular damage, opening new approaches to slowing aging and reducing its consequences.
Topics: Humans; DNA Damage; Aging; Organelles; DNA; Models, Biological
PubMed: 36846190
DOI: 10.1038/s43587-021-00150-3 -
Frontiers in Immunology 2022
Topics: DNA Damage; DNA Repair; Immunity
PubMed: 36254318
DOI: 10.3389/fimmu.2022.1034689 -
Biomolecules Dec 2022Developing B and T lymphocytes requires programmed DNA double-strand breaks followed by the activation of the DNA damage response (DDR) pathway and DNA repair [...].
Developing B and T lymphocytes requires programmed DNA double-strand breaks followed by the activation of the DNA damage response (DDR) pathway and DNA repair [...].
Topics: DNA Damage; DNA Repair; DNA Breaks, Double-Stranded; T-Lymphocytes
PubMed: 36671469
DOI: 10.3390/biom13010084 -
International Journal of Molecular... Nov 2023Following our first Special Issue, we are pleased to present this Special Issue in the , titled 'DNA Damage, DNA Repair, and Cancer: Second Edition' [...].
Following our first Special Issue, we are pleased to present this Special Issue in the , titled 'DNA Damage, DNA Repair, and Cancer: Second Edition' [...].
Topics: Humans; DNA Repair; DNA Damage; Neoplasms
PubMed: 38069158
DOI: 10.3390/ijms242316835 -
Trends in Endocrinology and Metabolism:... Jan 2024Computational models that measure biological age and aging rate regardless of chronological age are called aging clocks. The underlying counting mechanisms of the... (Review)
Review
Computational models that measure biological age and aging rate regardless of chronological age are called aging clocks. The underlying counting mechanisms of the intrinsic timers of these clocks are still unclear. Molecular mediators and determinants of aging rate point to the key roles of DNA damage, epigenetic drift, and inflammation. Persistent DNA damage leads to cellular senescence and the senescence-associated secretory phenotype (SASP), which induces cytotoxic immune cell infiltration; this further induces DNA damage through reactive oxygen and nitrogen species (RONS). I discuss the possibility that DNA damage (or the response to it, including epigenetic changes) is the fundamental counting unit of cell cycles and cellular senescence, that ultimately accounts for cell composition changes and functional decline in tissues, as well as the key intervention points.
Topics: Humans; Aging; Cellular Senescence; DNA Damage; Reactive Oxygen Species
PubMed: 37880054
DOI: 10.1016/j.tem.2023.09.007 -
Trends in Cell Biology Feb 2020Mounting evidence suggests that DNA damage plays a central role in aging. Multiple tiers of defense have evolved to reduce the accumulation of DNA damage, including... (Review)
Review
Mounting evidence suggests that DNA damage plays a central role in aging. Multiple tiers of defense have evolved to reduce the accumulation of DNA damage, including reducing damaging molecules, repairing DNA damage, and inducing senescence or apoptosis in response to persistent DNA damage. Mutations in or failure of these pathways can lead to accelerated or premature aging and age-related decline in vital organs, supporting the hypothesis that maintaining a pristine genome is paramount for human health. Understanding how we cope with DNA damage could inform on the aging process and further on how deficient DNA maintenance manifests in age-related phenotypes. This knowledge may lead to the development of novel interventions promoting healthspan.
Topics: Aging; Animals; Cellular Senescence; DNA Damage; DNA Repair; Genome; Humans; Mutation
PubMed: 31917080
DOI: 10.1016/j.tcb.2019.12.001 -
Cancer Radiotherapie : Journal de La... Oct 2022Radiotherapy (RT) is one of the main cancer treatments and grows in importance due to improved techniques. DNA damage caused by ionizing radiation creates DNA strand... (Review)
Review
Radiotherapy (RT) is one of the main cancer treatments and grows in importance due to improved techniques. DNA damage caused by ionizing radiation creates DNA strand breaks that trigger an intervention of DNA repair pathways involving numerous proteins and enzymes. In recent years, we have identified DNA repair inhibitors as targets for inhibiting cellular repair systems and thus causing cell death. Combining RT with these DNA repair inhibitors appears to be a new approach for cancer treatment, but safety and real efficiency of this combination in practice is unclear. Numerous trials are underway in various diseases and initial results are promising overall, yet remain controversial.
Topics: DNA; DNA Damage; DNA Repair; Humans
PubMed: 35987813
DOI: 10.1016/j.canrad.2022.06.019 -
The FEBS Journal Jul 2023The central nervous system is particularly susceptible to DNA repair deficiency, which renders a variety of neurodevelopmental and neurodegenerative disorders in humans.... (Review)
Review
The central nervous system is particularly susceptible to DNA repair deficiency, which renders a variety of neurodevelopmental and neurodegenerative disorders in humans. It is generally believed that DNA damage occurs upon repetitive replication and oxidative stress in highly proliferating neuroprogenitor cells (NPs), or due to high rates of metabolism and active neuronal activity in terminally differentiated neurons. DNA double-stranded breaks (DSBs) and single-stranded breaks (SSBs) constitute the most prevalent forms of DNA damage, which can result in neuronal apoptosis if unrepaired. Despite these notions, there are still gaps in our knowledge regarding the mechanism and specificity of DNA damage and repair in the neural development and the homeostasis of neural tissues. Recent studies have identified recurrent DSBs within neuronal long genes in NPs and 'programmed' SSBs in neuronal activity genes. However, the physiological function of these DNA breakages in the nervous system has not been so far explored. In this review, we summarise the recent advances in the field of DNA damage and DNA repair in neural development and neuropathies.
Topics: Humans; DNA Repair; DNA Breaks, Double-Stranded; Neurons; DNA Damage; DNA
PubMed: 35612788
DOI: 10.1111/febs.16535 -
International Journal of Molecular... Apr 2022Neurological complications directly impact the lives of hundreds of millions of people worldwide. While the precise molecular mechanisms that underlie neuronal cell loss... (Review)
Review
Neurological complications directly impact the lives of hundreds of millions of people worldwide. While the precise molecular mechanisms that underlie neuronal cell loss remain under debate, evidence indicates that the accumulation of genomic DNA damage and consequent cellular responses can promote apoptosis and neurodegenerative disease. This idea is supported by the fact that individuals who harbor pathogenic mutations in DNA damage response genes experience profound neuropathological manifestations. The review article here provides a general overview of the nervous system, the threats to DNA stability, and the mechanisms that protect genomic integrity while highlighting the connections of DNA repair defects to neurological disease. The information presented should serve as a prelude to the Special Issue "Genome Stability and Neurological Disease", where experts discuss the role of DNA repair in preserving central nervous system function in greater depth.
Topics: DNA Damage; DNA Repair; Genome; Genomic Instability; Humans; Neurodegenerative Diseases
PubMed: 35456958
DOI: 10.3390/ijms23084142 -
Chemical Society Reviews Oct 2020Cellular DNA is constantly chemically altered by exogenous and endogenous agents. As all processes of life depend on the transmission of the genetic information,... (Review)
Review
Cellular DNA is constantly chemically altered by exogenous and endogenous agents. As all processes of life depend on the transmission of the genetic information, multiple biological processes exist to ensure genome integrity. Chemically damaged DNA has been linked to cancer and aging, therefore it is of great interest to map DNA damage formation and repair to elucidate the distribution of damage on a genome-wide scale. While the low abundance and inability to enzymatically amplify DNA damage are obstacles to genome-wide sequencing, new developments in the last few years have enabled high-resolution mapping of damaged bases. Recently, a number of DNA damage sequencing library construction strategies coupled to new data analysis pipelines allowed the mapping of specific DNA damage formation and repair at high and single nucleotide resolution. Strikingly, these advancements revealed that the distribution of DNA damage is heavily influenced by chromatin states and the binding of transcription factors. In the last seven years, these novel approaches have revealed new genomic maps of DNA damage distribution in a variety of organisms as generated by diverse chemical and physical DNA insults; oxidative stress, chemotherapeutic drugs, environmental pollutants, and sun exposure. Preferred sequences for damage formation and repair have been elucidated, thus making it possible to identify persistent weak spots in the genome as locations predicted to be vulnerable for mutation. As such, sequencing DNA damage will have an immense impact on our ability to elucidate mechanisms of disease initiation, and to evaluate and predict the efficacy of chemotherapeutic drugs.
Topics: Antineoplastic Agents; Cisplatin; DNA; DNA Adducts; DNA Damage; DNA Repair; Guanine; High-Throughput Nucleotide Sequencing; Humans; Sequence Analysis, DNA
PubMed: 32968744
DOI: 10.1039/d0cs00647e