Do DNA Double-Strand Breaks Drive Aging?
Open accessAbstract
DNA double-strand breaks (DSBs) are rare, but highly toxic, lesions requiring orchestrated and conserved machinery to prevent adverse consequences, such as cell death and cancer-causing genome structural mutations. DSBs trigger the DNA damage response (DDR) that directs a cell to repair the break, undergo apoptosis, or become senescent. There is increasing evidence that the various endpoints of DSB processing by different cells and tissues are part of the aging phenotype, with each stage of the DDR associated with specific aging pathologies. In this Perspective, we discuss the possibility that DSBs are major drivers of intrinsic aging, highlighting the dynamics of spontaneous DSBs in relation to aging, the distinct age-related pathologies induced by DSBs, and the segmental progeroid phenotypes in humans and mice with genetic defects in DSB repair. A model is presented as to how DSBs could drive some of the basic mechanisms underlying age-related functional decline and death.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Ageing is consistently associated with increased DNA damage response in proliferating and non-proliferating cells, contributing to senescent cell accumulation with age.
“Ageing is one of the factors that is consistently associated with an increase in DDR in proliferating and non-proliferating cells, thus contributing significantly to the accumulation of senescent cells with age35,89”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [89]
In “DSBs, DSB processing and aging” (page unavailable), the paper reports that DNA-damage-associated γH2AX foci increase with age in multiple tissues, including fibroblasts and brain, and in senescent cells. The Abstract says DSB-triggered DDR can lead to senescence. But the paper does not establish that DDR activity consistently increases in both proliferating and non-proliferating cells or that this significantly causes senescent-cell accumulation; “DSB processing and repair as a function of age” also describes declines in some damage responses. (LLM, conf=0.85)
Experimental — accuracy not yet measuredDuring ageing, terminally differentiated cells can accumulate persistent DNA damage and DDR markers.
“during ageing terminally differentiated cells can accumulate persistent DNA damage and DDR markers35,89”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [89]
In “DSBs, DSB processing and aging” (page unavailable), the paper reports that persistent γH2AX foci, a DNA-damage-response marker, increase with age in several cells and tissues, including brain and liver. It also says unrepaired DSBs may accumulate with age, but does not establish that the observed foci represent unrepaired DNA damage or specifically identify terminally differentiated cells as the affected population. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
The DNA-damage response in human biology and disease
Jackson, S. P., & Bartek, J. (2009) · Nature · doi:10.1038/nature08467 · Cited by 6,092 · see citing works
The DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368 · see citing works
Chronic Health Conditions in Adult Survivors of Childhood Cancer
Oeffinger, K. C., Mertens, A. C., Sklar, C. A., Kawashima, T. I., Hudson, M. M., Meadows, A. T., Friedman, D. L., Marina, N. M., Hobbie, W. L., Kadan‐Lottick, N. S., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmsa060185 · Cited by 3,597 · see citing works
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway
Lieber, M. R. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.052308.093131 · Cited by 2,882 · see citing works
Hoeijmakers, J. H. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804615 · Cited by 2,239 · see citing works
An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045 · see citing works
Self-citationThe ATM protein kinase: regulating the cellular response to genotoxic stress, and more
Shiloh, Y., & Ziv, Y. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3546 · Cited by 1,649 · see citing works
Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6
Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., et al. (2006) · Cell · doi:10.1016/j.cell.2005.11.044 · Cited by 1,637 · see citing works
Playing the End Game: DNA Double-Strand Break Repair Pathway Choice
Chapman, J. R., Taylor, M. R. G., & Boulton, S. J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.07.029 · Cited by 1,629 · see citing works
Extrachromosomal rDNA circles—a cause of aging in yeast
Sinclair, D. A., & Guarente, L. (1997) · Cell · doi:10.1016/s0092-8674(00)80493-6 · Cited by 1,500 · see citing works
Repair Pathway Choices and Consequences at the Double-Strand Break
Ceccaldi, R., Rondinelli, B., & D’Andrea, A. D. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.07.009 · Cited by 1,499 · see citing works
Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia
Barlow, C., Hirotsune, S., Paylor, R. E., Liyanage, M., Eckhaus, M., Collins, F. S., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80086-0 · Cited by 1,450 · see citing works
Programmed cell senescence during mammalian embryonic development
Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., Rodríguez-Baeza, A., Varela-Nieto, I., Ruberte, J., Collado, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.019 · Cited by 1,428 · see citing works
Promoting Health and Longevity through Diet: From Model Organisms to Humans
Fontana, L., & Partridge, L. (2015) · Cell · doi:10.1016/j.cell.2015.02.020 · Cited by 1,245 · see citing works
Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age
Rossi, D. J., Bryder, D., Seita, J., Nussenzweig, A., Hoeijmakers, J., & Weissman, I. L. (2007) · Nature · doi:10.1038/nature05862 · Cited by 1,115 · see citing works
Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2
Sharan, S. K., Morimatsu, M., Albrecht, U., Lim, D., Regel, E., Dinh, C. Q., Sands, A., Gregor Eichele, C., Hasty, P., & Bradley, A. (1997) · Nature · doi:10.1038/386804a0 · Cited by 1,071 · see citing works
The sirtuin SIRT6 regulates lifespan in male mice
Kanfi, Y., Naiman, S., Amir, G., Peshti, V., Zinman, G., Nahum, L., Bar-Joseph, Z., & Cohen, H. Y. (2012) · Nature · doi:10.1038/nature10815 · Cited by 1,059 · see citing works
Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis
Moynahan, M. E., & Jasin, M. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2851 · Cited by 923 · see citing works
Hewitt, G., Jurk, D., Marques, F. D. M., Correia-Melo, C., Hardy, T., Gackowska, A., Anderson, R., Taschuk, M., Mann, J., & Passos, J. F. (2012) · Nature Communications · doi:10.1038/ncomms1708 · Cited by 908 · see citing works
SIRT6 Promotes DNA Repair Under Stress by Activating PARP1
Mao, Z., Hine, C., Tian, X., Van Meter, M., Au, M., Vaidya, A., Seluanov, A., & Gorbunova, V. (2011) · Science · doi:10.1126/science.1202723 · Cited by 867 · see citing works
DNA Repair Pathway Stimulated by the Forkhead Transcription Factor FOXO3a Through the Gadd45 Protein
Tran, H. G., Brunet, A., Grenier, J. M., Datta, S. R., Fornace, A. J., DiStefano, P. S., Chiang, L. W., & Greenberg, M. E. (2002) · Science · doi:10.1126/science.1068712 · Cited by 860 · see citing works
SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging
Oberdoerffer, P., Michan, S., McVay, M., Mostoslavsky, R., Vann, J., Park, S.-K., Hartlerode, A., Stegmuller, J., Hafner, A., Loerch, P., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.025 · Cited by 852 · see citing works
Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation
Fumagalli, M., Rossiello, F., Clerici, M., Barozzi, S., Cittaro, D., Kaplunov, J. M., Bucci, G., Dobreva, M., Matti, V., Beausejour, C. M., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2466 · Cited by 851 · see citing works
How stem cells age and why this makes us grow old
Sharpless, N. E., & DePinho, R. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2241 · Cited by 843 · see citing works
Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks
Sedelnikova, O. A., Horikawa, I., Zimonjic, D. B., Popescu, N. C., Bonner, W. M., & Barrett, J. C. (2004) · Nature Cell Biology · doi:10.1038/ncb1095 · Cited by 790 · see citing works
Ruzankina, Y., Pinzon‐Guzman, C., Asare, A., Ong, T., Pontano, L. L., Cotsarelis, G., Zediak, V. P., Velez, M., Bhandoola, A., & Brown, E. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.03.002 · Cited by 780 · see citing works
Repair and Genetic Consequences of Endogenous DNA Base Damage in Mammalian Cells
Barnes, D. E., & Lindahl, T. (2004) · Annual Review of Genetics · doi:10.1146/annurev.genet.38.072902.092448 · Cited by 753 · see citing works
Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer
Vilenchik, M. M., & Knudson, A. G. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2135498100 · Cited by 717 · see citing works
DNA damage response and cellular senescence in tissues of aging mice
Wang, C., Jurk, D., Maddick, M., Nelson, G., Martin‐Ruiz, C., & Von Zglinicki, T. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00481.x · Cited by 696 · see citing works
A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis
Niedernhofer, L. J., Garinis, G. A., Raams, A., Lalai, A. S., Robinson, A. R., Appeldoorn, E., Odijk, H., Oostendorp, R., Ahmad, A., van Leeuwen, W., et al. (2006) · Nature · doi:10.1038/nature05456 · Cited by 669 · see citing works
Self-citationReplication stress is a potent driver of functional decline in ageing haematopoietic stem cells
Flach, J., Bakker, S. T., Mohrin, M., Conroy, P. C., Pietras, E. M., Reynaud, D., Alvarez, S., Diolaiti, M. E., Ugarte, F., Forsberg, E. C., et al. (2014) · Nature · doi:10.1038/nature13619 · Cited by 650 · see citing works
Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated Pathway?
Sfeir, A., & Symington, L. S. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.08.006 · Cited by 636 · see citing works
Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells
Walter, D., Lier, A., Geiselhart, A., Thalheimer, F. B., Huntscha, S., Sobotta, M. C., Moehrle, B., Brocks, D., Bayindir, I., Kaschutnig, P., et al. (2015) · Nature · doi:10.1038/nature14131 · Cited by 619 · see citing works
Association of <i>FOXO3A</i> variation with human longevity confirmed in German centenarians
Flachsbart, F., Caliebe, A., Kleindorp, R., Blanché, H., von Eller-Eberstein, H., Nikolaus, S., Schreiber, S., & Nebel, A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809594106 · Cited by 572 · see citing works
Accumulation of senescent cells in Mitotic tissue of aging primates
Jeyapalan, J. C., Ferreira, M., Sedivy, J. M., & Herbig, U. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.008 · Cited by 571 · see citing works
Aging and Genome Maintenance: Lessons from the Mouse?
Hasty, P., Campisi, J., Hoeijmakers, J., van Steeg, H., & Vijg, J. (2003) · Science · doi:10.1126/science.1079161 · Cited by 553 · cited 2× · see citing works
“Nevertheless, important new findings based on such models have provided new insights into possible causes of aging (Hasty et al., 2003).”
BackgroundSelf-citationImpairment of BRCA1-Related DNA Double-Strand Break Repair Leads to Ovarian Aging in Mice and Humans
Titus, S., Li, F., Stobezki, R., Akula, K., Ünsal, E., Jeong, K., Dickler, M. N., Robson, M. E., MOY, F. H., Goswami, S., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3004925 · Cited by 523 · see citing works
Frequent chromosomal translocations induced by DNA double-strand breaks
Richardson, C., & Jasin, M. (2000) · Nature · doi:10.1038/35015097 · Cited by 517 · see citing works
Niedernhofer, L. J., Odijk, H., Budzowska, M., van Drunen, E., Maas, A., Theil, A. F., de Wit, J., Jaspers, N. G. J., Beverloo, H. B., Hoeijmakers, J. H. J., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.13.5776-5787.2004 · Cited by 493 · see citing works
Frank, K. M., Sharpless, N. E., Gao, Y., Sekiguchi, J., Ferguson, D. O., Zhu, C., Manis, J. P., Horner, J. W., DePinho, R. A., & Alt, F. W. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80264-6 · Cited by 492 · see citing works
Chiarle, R., Zhang, Y., Frock, R. L., Lewis, S. M., Molinié, B., Ho, Y.-J., Myers, D. R., Choi, V. W., Compagno, M., Malkin, D. J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.07.049 · Cited by 475 · see citing works
Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing
Crosetto, N., Mitra, A., Silva, M. J., Bienko, M., Dojer, N., Wang, Q., Karaca, E., Chiarle, R., Skrzypczak, M., Ginalski, K., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2408 · Cited by 465 · see citing works
Essential role of limiting telomeres in the pathogenesis of Werner syndrome
Chang, S., Multani, A. S., Cabrera, N. G., Naylor, M. L., Laud, P., Lombard, D., Pathak, S., Guarente, L., & DePinho, R. A. (2004) · Nature Genetics · doi:10.1038/ng1389 · Cited by 462 · see citing works
Beerman, I., Seita, J., Inlay, M. A., Weissman, I. L., & Rossi, D. J. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.04.016 · Cited by 445 · see citing works
Zhu, C., Bogue, M. A., Lim, D., Hasty, P., & Roth, D. B. (1996) · Cell · doi:10.1016/s0092-8674(00)80111-7 · Cited by 433 · see citing works
A means to a DNA end: the many roles of Ku
Downs, J. A., & Jackson, S. P. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1367 · Cited by 393 · see citing works
Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing
Wong, K.-K., Maser, R. S., Bachoo, R. M., Menon, J., Carrasco, D. R., Gu, Y., Alt, F. W., & DePinho, R. A. (2003) · Nature · doi:10.1038/nature01385 · Cited by 375 · see citing works
Ataxia-telangiectasia and cellular responses to DNA damage.
Meyn, M. S. (1995) · PubMed · Cited by 374 · see citing works
Xu, X., Qiao, W., Linke, S. P., Cao, L., Li, W., Furth, P. A., Harris, C. C., & Deng, C. (2001) · Nature Genetics · doi:10.1038/90108 · Cited by 372 · see citing works
Deletion of Ku86 causes early onset of senescence in mice
Vogel, H., Lim, D.-S., Karsenty, G., Finegold, M., & Hasty, P. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.19.10770 · Cited by 368 · see citing works
DNA damage and ageing: new-age ideas for an age-old problem
Garinis, G. A., van der Horst, G. T. J., Vijg, J., & H.J. Hoeijmakers, J. (2008) · Nature Cell Biology · doi:10.1038/ncb1108-1241 · Cited by 366 · see citing works
Self-citationChromosomal Translocations in Human Cells Are Generated by Canonical Nonhomologous End-Joining
Ghezraoui, H., Piganeau, M., Renouf, B., Renaud, J.-B., Sallmyr, A., Ruis, B., Oh, S., Tomkinson, A. E., Hendrickson, E. A., Giovannangeli, C., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.002 · Cited by 351 · cited 1× · see citing works
“NHEJ is error prone because end processing can lead to small base pair deletions and translocations (Ghezraoui et al., 2014; Lieber, 2010).”
BackgroundDNA double-strand break repair pathway choice and cancer
Aparicio, T., Baer, R., & Gautier, J. (2014) · DNA Repair · doi:10.1016/j.dnarep.2014.03.014 · Cited by 347 · see citing works
Accelerated telomere shortening in ataxia telangiectasia
Metcalfe, J. A., Parkhill, J., Campbell, L. J., Stacey, M. W., Biggs, P., Byrd, P. J., & Taylor, A. M. R. (1996) · Nature Genetics · doi:10.1038/ng0796-350 · Cited by 338 · see citing works
DNA damage foci: Meaning and significance
Rothkamm, K., Barnard, S. G. R., Moquet, J., Ellender, M., Rana, Z., & Burdak‐Rothkamm, S. (2015) · Environmental and Molecular Mutagenesis · doi:10.1002/em.21944 · Cited by 335 · see citing works
Ness, K. K., Krull, K. R., Jones, K., Mulrooney, D. A., Armstrong, G. T., Green, D. M., Chemaitilly, W., Smith, W. A., Wilson, C. L., Sklar, C. A., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.52.2268 · Cited by 334 · see citing works
Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging
Rübe, C. E., Fricke, A., Widmann, T. A., Fürst, T., Madry, H., Pfreundschuh, M., & Rübe, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017487 · Cited by 307 · see citing works
ERCC1-XPF Endonuclease Facilitates DNA Double-Strand Break Repair
Ahmad, A., Robinson, A. R., Duensing, A. U., van Drunen, E., Beverloo, H. B., Weisberg, D. B., Hasty, P., Hoeijmakers, J. H. J., & Niedernhofer, L. J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00293-08 · Cited by 298 · see citing works
The RecQ DNA Helicases in DNA Repair
Bernstein, K. A., Gangloff, S., & Rothstein, R. J. (2010) · Annual Review of Genetics · doi:10.1146/annurev-genet-102209-163602 · Cited by 297 · see citing works
Cao, L., Li, W., Kim, S., Brodie, S. G., & Deng, C.-X. (2003) · Genes & Development · doi:10.1101/gad.1050003 · Cited by 293 · see citing works
DNA end joining becomes less efficient and more error-prone during cellular senescence
Seluanov, A., Mittelman, D., Pereira-Smith, O. M., Wilson, J. H., & Gorbunova, V. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400726101 · Cited by 278 · see citing works
Persistent γH2AX: A promising molecular marker of DNA damage and aging
Siddiqui, M. S., François, M., Fenech, M. F., & Leifert, W. R. (2015) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2015.07.001 · Cited by 266 · see citing works
Feng, Z., Hu, W., Teresky, A. K., Hernando, E., Cordon-Cardo, C., & Levine, A. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708043104 · Cited by 264 · see citing works
Rapid accumulation of genome rearrangements in liver but not in brain of old mice
Dollé, M. E. T., Giese, H., Hopkins, C. L., Martus, H., Hausdorff, J. M., & Vijg, J. (1997) · Nature Genetics · doi:10.1038/ng1297-431 · Cited by 248 · see citing works
Self-citationDistinct spectra of somatic mutations accumulated with age in mouse heart and small intestine
Dollé, M. E. T., Snyder, W. K., Gossen, J. A., Lohman, P. H. M., & Vijg, J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.15.8403 · Cited by 242 · see citing works
Self-citationHierarchical deterioration of body systems in Werner's syndrome: Implications for normal ageing
Goto, M. (1997) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(97)00111-5 · Cited by 240 · see citing works
Radiation Dose and Breast Cancer Risk in the Childhood Cancer Survivor Study
Inskip, P. D., Robison, L. L., Stovall, M. A., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.7738 · Cited by 234 · see citing works
DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice
Suberbielle, E., Djukic, B., Evans, M., Kim, D. H., Taneja, P., Wang, X., Finucane, M. M., Knox, J. A., Ho, K., Devidze, N., et al. (2015) · Nature Communications · doi:10.1038/ncomms9897 · Cited by 202 · see citing works
Iliakis, G. E., Murmann-Konda, T., & Soni, A. (2015) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2015.07.001 · Cited by 199 · see citing works
Mutations in the <i>WRN</i> Gene in Mice Accelerate Mortality in a p53-Null Background
Lombard, D. B., Beard, C., Johnson, B., Marciniak, R. A., Dausman, J., Bronson, R., Buhlmann, J. E., Lipman, R., Curry, R., Sharpe, A., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.9.3286-3291.2000 · Cited by 187 · see citing works
Mao, Z., Tian, X., Van Meter, M., Ke, Z., Gorbunova, V., & Seluanov, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200583109 · Cited by 176 · see citing works
BRCA Mutations, DNA Repair Deficiency, and Ovarian Aging1
Oktay, K., Turan, V., Titus, S., Stobezki, R., & Liu, L. (2015) · Biology of Reproduction · doi:10.1095/biolreprod.115.132290 · Cited by 165 · see citing works
Deletion of Ku70, Ku80, or Both Causes Early Aging without Substantially Increased Cancer
Li, H., Vogel, H. S., Holcomb, V. B., Gu, Y., & Hasty, P. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00785-07 · Cited by 151 · see citing works
Shorter telomeres, accelerated ageing and increased lymphoma in DNA‐PKcs‐deficient mice
Espejel, S., Martı́n, M., Klatt, P., Martín‐Caballero, J., Flores, J. M., & Blasco, M. A. (2004) · EMBO Reports · doi:10.1038/sj.embor.7400127 · Cited by 127 · see citing works
Ageing, repetitive genomes and DNA damage
Lieber, M. R., & Karanjawala, Z. E. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1281 · Cited by 126 · see citing works
Human RECQ helicases: Roles in DNA metabolism, mutagenesis and cancer biology
Monnat, R. J. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2010.10.002 · Cited by 122 · see citing works
Knock-In Reporter Mice Demonstrate that DNA Repair by Non-homologous End Joining Declines with Age
Vaidya, A. M., Mao, Z., Tian, X., Spencer, B., Seluanov, A., & Gorbunova, V. A. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004511 · Cited by 119 · see citing works
Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats
Warmerdam, D. O., van den Berg, J., & Medema, R. H. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.02.048 · Cited by 112 · see citing works
White, R. R., Milholland, B., de Bruin, A., Curran, S., Laberge, R.-M., van Steeg, H., Campisi, J., Maslov, A. Y., & Vijg, J. (2015) · Nature Communications · doi:10.1038/ncomms7790 · Cited by 107 · see citing works
Self-citationThe Biologic Effects of Pile Radiations
Henshaw, P. S., Riley, E. F., & Stapleton, G. E. (1947) · Radiology · doi:10.1148/49.3.349 · Cited by 98 · see citing works
Schneider, L., Pellegatta, S., Favaro, R., Pisati, F., Roncaglia, P., Testa, G., Nicolis, S. K., Finocchiaro, G., & d’Adda di Fagagna, F. (2013) · Stem Cell Reports · doi:10.1016/j.stemcr.2013.06.004 · Cited by 92 · see citing works
Broad segmental progeroid changes in short-lived <i>Ercc1</i> <sup>−/Δ7</sup> mice
Dollé, M. E. T., Kuiper, R. V., Roodbergen, M., Robinson, J., de Vlugt, S., Wijnhoven, S. W. P., Beems, R. B., de la Fonteyne, L., de With, P., van der Pluijm, I., et al. (2011) · Pathobiology of Aging & Age-related Diseases · doi:10.3402/pba.v1i0.7219 · Cited by 91 · see citing works
Self-citationDNA double strand break repair, aging and the chromatin connection
Gorbunova, V., & Seluanov, A. (2016) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2016.02.004 · Cited by 87 · see citing works
DNA double strand break repair in brain: Reduced NHEJ activity in aging rat neurons
Vyjayanti, V. N., & Rao, K. S. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.09.053 · Cited by 83 · see citing works
The Contribution of Alu Elements to Mutagenic DNA Double-Strand Break Repair
Morales, M. E., White, T., Streva, V. A., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005016 · Cited by 83 · see citing works
Dollé, M. E. T., & Vijg, J. (2002) · Genome Research · doi:10.1101/gr.125502 · Cited by 66 · see citing works
Self-citationVijg, J. (2007) · doi:10.1093/acprof:oso/9780198569237.001.0001 · Cited by 63 · see citing works
Self-citationControlled DNA double-strand break induction in mice reveals post-damage transcriptome stability
Kim, J., Sturgill, D., Tran, A. D., Sinclair, D. A., & Oberdoerffer, P. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1482 · Cited by 62 · see citing works
Stem Cell-Specific Mechanisms Ensure Genomic Fidelity within HSCs and upon Aging of HSCs
Moehrle, B., Nattamai, K., Brown, A., Florian, M. C., Ryan, M. A., Vogel, M., Bliederhaeuser, C., Soller, K., Prows, D. R., Abdollahi, A., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.11.030 · Cited by 57 · see citing works
RhoB Promotes γH2AX Dephosphorylation and DNA Double-Strand Break Repair
Mamouni, K., Cristini, A., Guirouilh‐Barbat, J., Monferran, S., Lemarié, A., Faye, J., López, B. S., Favre, G., & Sordet, O. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.01525-13 · Cited by 43 · see citing works
Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes
Hu, L., Kim, T. M., Son, M. Y., Kim, S.-A., Holland, C., Tateishi, S., Kim, D. H., Yew, P. R., Montagna, C., Dumitrache, L. C., et al. (2013) · Nature · doi:10.1038/nature12500 · Cited by 42 · see citing works
High-throughput sequencing in mutation detection: A new generation of genotoxicity tests?
Maslov, A. Y., Quispe‐Tintaya, W., Gorbacheva, T., White, R. R., & Vijg, J. (2015) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2015.03.014 · Cited by 42 · see citing works
Self-citationLee, J.-E., Heo, J., Park, S., Kim, J., Kho, Y., Kang, H., Chung, H. Y., Yoon, J. L., & Lee, J. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.07.009 · Cited by 25 · see citing works
White, R. R., Sung, P., Vestal, C. G., Benedetto, G., Cornelio, N., & Richardson, C. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084379 · Cited by 22 · see citing works
Self-citationQuispe‐Tintaya, W., Gorbacheva, T., Lee, M., Махортов, С. Д., Popov, V. N., Vijg, J., & Maslov, A. Y. (2016) · Nature Methods · doi:10.1038/nmeth.3893 · Cited by 17 · see citing works
Self-citationBiological Effects of Gamma Irradiation (Series II)
Russ, S., & Scott, G. M. (1939) · British Journal of Radiology · doi:10.1259/0007-1285-12-139-440 · Cited by 14 · see citing works
The Progeroid Phenotype of Ku80 Deficiency Is Dominant over DNA-PKCS Deficiency
Reiling, E., Dollé, M. E. T., Youssef, S. A., Lee, M., Nagarajah, B., Roodbergen, M., de With, P., de Bruin, A., Hoeijmakers, J. H. J., Vijg, J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093568 · Cited by 13 · see citing works
Self-citationMaslov, A. Y., Metrikin, M., & Vijg, J. (2009) · BioTechniques · doi:10.2144/000113237 · Cited by 4 · see citing works
Self-citationWarren, S. (1971) · Europe PMC (PubMed Central) · Cited by 1 · see citing works
Sukup-Jackson, M. R., Kiraly, O., Kay, J. E., Na, L., Rowland, E. A., Winther, K. E., Chow, D. N., Kimoto, T., Matsuguchi, T., Jonnalagadda, V. S., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004299 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cellular senescence in ageing: from mechanisms to therapeutic opportunities
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00314-w · Cited by 2,277 · see citing works
Loss of epigenetic information as a cause of mammalian aging
Yang, J.-H., Hayano, M., Griffin, P. T., Amorim, J. A., Bonkowski, M. S., Apostolides, J. K., Salfati, E. L., Blanchette, M., Munding, E. M., Bhakta, M., et al. (2023) · Cell · doi:10.1016/j.cell.2022.12.027 · Cited by 643 · see citing works
NAD(+) in aging: molecular mechanisms and translational implications
Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.08.001 · Cited by 501 · see citing works
SIRT6 is responsible for more efficient DNA double-strand break repair in long-lived species
Tian, X., Firsanov, D., Zhang, Z., Cheng, Y., Luo, L., Tombline, G., Tan, R., Simon, M., Henderson, S., Steffan, J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.043 · Cited by 353 · see citing works
Self-citationOgrodnik, M. (2021) · Aging Cell · doi:10.1111/acel.13338 · Cited by 349 · see citing works
Role of Cellular Senescence in Type II Diabetes
Narasimhan, A., Flores, R. R., Robbins, P. D., & Niedernhofer, L. J. (2021) · Endocrinology · doi:10.1210/endocr/bqab136 · Cited by 133 · see citing works
Senescent Microglia: The Key to the Ageing Brain?
Greenwood, E. K., & Brown, D. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094402 · Cited by 84 · see citing works
Toward understanding genomic instability, mitochondrial dysfunction and aging
Fakouri, N. B., Hou, Y., Demarest, T. G., Christiansen, L. S., Okur, M. N., Mohanty, J. G., Croteau, D. L., & Bohr, V. A. (2019) · The FEBS Journal · doi:10.1111/febs.14663 · Cited by 77 · see citing works
Profiling DNA break sites and transcriptional changes in response to contextual fear learning
Stott, R. T., Kritsky, O., & Tsai, L.-H. (2021) · PLOS ONE · doi:10.1371/journal.pone.0249691 · Cited by 62 · see citing works
Bar, S., Hilsabeck, T. A. U., Pattavina, B., López-Domínguez, J. A., Basisty, N., Bons, J., Watson, M., Schilling, B., Campisi, J., Kapahi, P., et al. (2025) · Aging · doi:10.18632/aging.206224 · Cited by 3 · see citing works
- Authors
- White, R. R., & Vijg, J.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- White, Ryan R.
- Vijg, Jan
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 63
- Issue
- 5
- Pages
- 729-738
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5012315
- OpenAlex
- W2513448306
- Cited by
- 232
- References
- 101
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 25 · 2023: 22 · 2022: 32 · 2021: 31 · 2020: 26 · 2019: 26 · 2018: 19 · 2017: 14 · 2016: 4
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Glenn Foundation for Medical Research
- National Institutes of Health
- National Institute on Aging (P01AG017242, P01AG047200)
- National Cancer Institute (R01CA180126)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- DNA double-strand breaks, aging, DNA damage response, DNA repair, cellular senescence, apoptosis, spontaneous DNA damage, age-related diseases, progeroid phenotype, age-related functional decline
- MeSH terms
- Ku Autoantigen, MRE11 Homologue Protein, Aging, Animals, DNA, DNA Repair, DNA-Binding Proteins, Endonucleases, Gene Expression Regulation, Humans, Models, Genetic, Nuclear Proteins, Progeria, Saccharomyces cerevisiae, Signal Transduction, Cellular Senescence, Acid Anhydride Hydrolases, Cell Cycle Proteins, BRCA1 Protein, DNA Repair Enzymes, Mice, DNA Breaks, Double-Stranded
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
