DNA damage responses and p53 in the aging process
Open accessAbstract
The genome is constantly attacked by genotoxic insults. DNA damage has long been established as a cause of cancer development through its mutagenic consequences. Conversely, radiation therapy and chemotherapy induce DNA damage to drive cells into apoptosis or senescence as outcomes of the DNA damage response (DDR). More recently, DNA damage has been recognized as a causal factor for the aging process. The role of DNA damage in aging and age-related diseases is illustrated by numerous congenital progeroid syndromes that are caused by mutations in genome maintenance pathways. During the past 2 decades, understanding how DDR drives cancer development and contributes to the aging process has progressed rapidly. It turns out that the DDR factor p53 takes center stage during tumor development and also plays an important role in the aging process. Studies in metazoan models ranging from Caenorhabditis elegans to mammals have revealed cell-autonomous and systemic DDR mechanisms that orchestrate adaptive responses that augment maintenance of the aging organism amid gradually accumulating DNA damage.
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Incomplete DNA repair may contribute to accumulation of DNA lesions, DDR activation and widespread chromatin changes during ageing.
“Incomplete DNA repair may further contribute to the accumulation of DNA lesions and DDR activation as well as to the widespread chromatin changes seen in different cell types and at the organismal level during ageing90,91”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [90]
In “Persistent DNA damage: a driving force of aging” (page unavailable), the paper says unrepaired lesions can persist and activate the DDR, and that limited repair in aged hematopoietic stem cells leads to gradual DNA-damage accumulation. Our copy does not link incomplete repair to widespread chromatin changes across cell types or at the organismal level during aging. (LLM, conf=0.88)
Experimental — accuracy not yet measuredmROS initiate signals that activate several pathways that protect mitochondria from oxidative stress; these pathways slow aging, inhibit cell death and may result in lifespan extension.
“In addition to inducing protection of nuclear DNA from oxidative damage, mROS initiate signals that activate several pathways that protect mitochondria from oxidative stress. These pathways slow aging, inhibit cell death and may result in lifespan extension [67,108,109].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [109]
Failure of the DDR to properly repair DNA results in accumulation of DNA damage and subsequently cellular senescence.
“Failure of the DDR to properly repair DNA results in the accumulation of DNA damage and subsequently cellular senescence, and as such it plays a crucial role in maintaining the genomic integrity and cellular function [92, 121, 168].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [121]
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References 113 · Cited by 377
Research works printed but not linked: 1
- [102]Garinis GA Uittenboogaard LM Stachelscheid H Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity Nat Cell Biol 2009 11 5 604 615 19363488 PMC2782455
- Authors
- Ou, H.-L., & Schumacher, B.
- Affiliations
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- University of Cologne (DE)
- Corresponding author
- Schumacher, Björn
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2018-02-01
- Volume
- 131
- Issue
- 5
- Pages
- 488-495
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC6839964
- OpenAlex
- W2769923893
- Semantic Scholar
- 4aefa712ad7b495c4c34fbcf1469c85e91a31db2
- Cited by
- 377
- References
- 113
- Citations by year
- 2026: 26 · 2025: 55 · 2024: 58 · 2023: 63 · 2022: 53 · 2021: 62 · 2020: 34 · 2019: 18 · 2018: 8
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- European Commission (316964, 316354, 316390)
- European Cooperation in Science and Technology (BM1408, GENiE, BM1408)
- Deutsche Forschungsgemeinschaft (SFB829, KFO286, SFB 670, SCHU 2494/3‐1, FLAG-ERA JTC 2015)
- Deutsche Krebshilfe (109453)
- FP7 Ideas: European Research Council (260383)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- DNA damage response, p53, aging, age-related diseases, progeroid syndromes, genome maintenance, genotoxicity, carcinogenesis, apoptosis, cellular senescence, Caenorhabditis elegans
- MeSH terms
- Aging, Animals, DNA Damage, Humans, Tumor Suppressor Protein p53, Cellular Senescence
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