Impact of genomic damage and ageing on stem cell function
Open accessAbstract
Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells.
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Defects in DNA repair systems of stem cells accelerate the accumulation of genome instability in lineage-primed progenitor cells during aging.
“Quite often, defects in DNA repair systems of stem cells accelerate the accumulation of genome instability in lineage-primed progenitor cells during aging [46].”
From Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging (2016) · cites this paper as [46]
Defects in ATM lead to accumulation of genomic damage and premature exhaustion of the stem cell pool in various tissues, including the skin.
“Although not a bona fide DNA repair gene, defects in ATM lead to accumulation of genomic damage and premature exhaustion of the stem cell pool in various tissues, including the skin [46].”
From Ultraviolet Radiation‐Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging (2016) · cites this paper as [46]
DDR pathways that safeguard genomic integrity may show reduced activity in stem cells with age.
“These observations suggest that DDR pathways, evolved to safeguard genomic integrity and maximize survival of the organism13,44–46, may show reduced activity in stem cells with age.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [46]
Loss of homeostasis in aging tissues might create a microenvironment that favors selection of stem cells with higher self-renewal but also neoplastic potential.
“Some studies suggest that the ensuing loss of homeostasis in aging tissues might further create a microenvironment that favors the selection of stem cells with higher self-renewal but also neoplastic potentials46.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [46]
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Self-citationp21 Both Attenuates and Drives Senescence and Aging in BubR1 Progeroid Mice
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Wnt7a treatment ameliorates muscular dystrophy
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Immunoaging induced by hematopoietic stem cell aging
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Self-citationShort Telomeres in ESCs Lead to Unstable Differentiation
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Declining lymphoid progenitor fitness promotes aging-associated leukemogenesis
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Self-citationSystemic DNA damage responses: organismal adaptations to genome instability
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Inflammation, fracture and bone repair
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“Cellular and molecular characterization of non-union tissues has shown that senescent MSCs exhibit a reduced capacity to differentiate into mature, functional osteoblasts [148,149].”
BackgroundMesenchymal stem cell-macrophage crosstalk and bone healing
Pajarinen, J., Lin, T., Gibon, E., Kohno, Y., Maruyama, M., Nathan, K., Lu, L. Y., Yao, Z., & Goodman, S. B. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2017.12.025 · Cited by 1,011 · see citing works
“overexpression of p53, p21, BAX or MYC genes, among other changes [72-75].”
BackgroundMechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD
Ferenbach, D. A., & Bonventre, J. V. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.3 · Cited by 880 · see citing works
Stem cell aging: mechanisms, regulators and therapeutic opportunities
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The effects of aging in the hippocampus and cognitive decline
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“Another possibility is that depletion of the NSC pool could be a consequence of an increase in the number of stem cells becoming senescent due to telomeric attrition and/or DNA damage that accumulates with aging (Behrens et al., 2014).”
Interventions to slow aging in humans: are we ready?
Longo, V. D., Antebi, A., Bartke, A., Barzilai, N., Brown‐Borg, H. M., Caruso, C., Curiel, T. J., Cabo, R., Franceschi, C., Gems, D., et al. (2015) · Aging Cell · doi:10.1111/acel.12338 · Cited by 592 · see citing works
“AMPK activation generates insulin-sensitizing effects resulting in increased glucose uptake in skeletal muscles, and decreased hepatic glucose production and enhanced fatty acid oxidation in several tissues (Ruderman & Prentki, 2004; Ruderman et al. , 2013).”
Self-citationBiomarkers of cellular senescence and skin aging
Wang, A. S., & Dreesen, O. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00247 · Cited by 404 · see citing works
“Acute UV radiation results in sunburns, aberrant pigmentation and immune suppression, whilst chronic exposure is associated with premature skin aging and a predisposition to develop malignancies (de Gruijl, 1999; Ichihashi et al., 2003; Quan et al., 2009; Behrens et al., 2014; Rittié and Fisher, 2015).”
BackgroundDNA damage responses and p53 in the aging process
Ou, H.-L., & Schumacher, B. (2018) · Blood · doi:10.1182/blood-2017-07-746396 · Cited by 377 · see citing works
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“The accrual of mutations by HSCs promotes aging-related disorders other than cancer, such as bone marrow failure and anemia (Behrens et al., 2014).”
BackgroundPanich, U., Sittithumcharee, G., Rathviboon, N., & Jirawatnotai, S. (2016) · Stem Cells International · doi:10.1155/2016/7370642 · Cited by 374 · see citing works
“Although not a bona fide DNA repair gene, defects in ATM lead to accumulation of genomic damage and premature exhaustion of the stem cell pool in various tissues, including the skin [46].”
Inflamm-aging of hematopoiesis, hematopoietic stem cells, and the bone marrow microenvironment
Kovtonyuk, L. V., Fritsch, K., Feng, X., Manz, M. G., & Takizawa, H. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00502 · Cited by 371 · see citing works
Meiners, S., Eickelberg, O., & Königshoff, M. (2015) · European Respiratory Journal · doi:10.1183/09031936.00186914 · Cited by 340 · see citing works
Cellular and epigenetic drivers of stem cell ageing
Ermolaeva, M., Neri, F., Ori, A., & Rudolph, K. L. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0020-3 · Cited by 272 · see citing works
Self-citationSenescence in COPD and Its Comorbidities
Barnes, P. J. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034314 · Cited by 276 · see citing works
Schwartz, S. D., Tan, G. S. W., Hosseini, H., & Nagiel, A. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18681 · Cited by 247 · see citing works
Cancers make their own luck: theories of cancer origins
Jassim, A., Rahrmann, E. P., Simons, B. D., & Gilbertson, R. J. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00602-5 · Cited by 226 · see citing works
Mechanisms of development of multimorbidity in the elderly
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Neri, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102406 · Cited by 188 · see citing works
“Both in vivo [61] and in vitro aging should be considered.”
BackgroundUnderstanding intrinsic hematopoietic stem cell aging
Mejía-Ramírez, E., & Florian, M. C. (2019) · Haematologica · doi:10.3324/haematol.2018.211342 · Cited by 191 · see citing works
Epigenetic Control of Stem Cell Potential during Homeostasis, Aging, and Disease
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“Indeed, mounting evidence indicates that degenerative aging-associated changes in adult stem cells are a central driver of many age-related phenotypes (reviewed in Oh et al., 2014; Liu and Rando, 2011; Behrens et al., 2014; Rossi et al., 2008).”
Aging-Induced Stem Cell Mutations as Drivers for Disease and Cancer
Adams, P. D., Jasper, H., & Rudolph, K. L. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.05.002 · Cited by 179 · see citing works
“The decline in functional capacity and genetic integrity of adult tissue stem cells is thought to be a major factor in the decline in tissue maintenance and the increase in cancer formation during aging (Behrens et al., 2014; Rando, 2006).”
BackgroundSelf-citationAging disrupts cell subpopulation dynamics and diminishes the function of mesenchymal stem cells
Duscher, D., Rennert, R. C., Januszyk, M., Anghel, E. L., Maan, Z. N., Whittam, A. J., Perez, M. G., Kosaraju, R. S., Hu, M. S.-M., Walmsley, G. G., et al. (2014) · Scientific Reports · doi:10.1038/srep07144 · Cited by 169 · see citing works
FOXM1: A key oncofoetal transcription factor in health and disease
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Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis
Mavragani, I. V., Nikitaki, Z., Souli, M., Aziz, A., Nowsheen, S., Aziz, K., Rogakou, E. P., & Georgakilas, A. G. (2017) · Cancers · doi:10.3390/cancers9070091 · Cited by 177 · see citing works
SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation
Hayakawa, T., Iwai, M., Aoki, S., Takimoto, K., Maruyama, M., Maruyama, W., & Motoyama, N. (2015) · PLOS ONE · doi:10.1371/journal.pone.0116480 · Cited by 170 · see citing works
“DNA damage accumulated in stem cells from several tissues including hematopoietic stem cells and satellite cells, leading to their functional inability [47–52].”
BackgroundAging, Clonality, and Rejuvenation of Hematopoietic Stem Cells
Akunuru, S., & Geiger, H. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.06.003 · Cited by 172 · see citing works
“Mechanisms Contributing to HSC Aging and Disease Environmental (such as aging microenvironment, niche interactions, or radiation) and cellintrinsic stress (such as metabolic and replicative stress), along with altered stress responses in aged HSCs, result in DNA damage and an increased frequency of genomic mutations […”
BackgroundHallmarks of progeroid syndromes: lessons from mice and reprogrammed cells
Carrero, D., Soria-Valles, C., & López-Otín, C. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.024711 · Cited by 153 · see citing works
“The ageing process is accompanied by a decrease in tissue regeneration and homeostasis, due to a decline in stem cell functions as a consequence of DNA damage, changes in tissue environment and alterations in tumour suppressor gene expression (Behrens et al., 2014).”
Intestinal epithelial barrier functions in ageing
Branca, J. J. V., Gulisano, M., & Nicoletti, C. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100938 · Cited by 157 · see citing works
Impact of risk factors on early cancer evolution
Weeden, C. E., Hill, W., Lim, E. L., Gronroos, E. C., & Swanton, C. (2023) · Cell · doi:10.1016/j.cell.2023.03.013 · Cited by 143 · see citing works
FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence
Macedo, J. C., Vaz, S., Bakker, B., Ribeiro, R., Bakker, P. L., Escandell, J. M., Ferreira, M. G., Medema, R., Foijer, F., & Logarinho, E. (2018) · Nature Communications · doi:10.1038/s41467-018-05258-6 · Cited by 131 · see citing works
Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging
Li, X., Wang, J.-Q., Wang, L.-Y., Gao, Y., Feng, G.-H., Li, G., Zou, J., Yu, M., Li, Y., Liu, C., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00964-6 · Cited by 120 · see citing works
“Although we did not detect adrenic acid, it is reported that ELOVL2 knockout also increases the content of adrenic acid.(27) Using Oil red O staining, we observed substantial accumulation of fatty acids in hepatocytes in both WT-O and −/− Y mice (Fig.”
BackgroundBiological and molecular profile of fracture non‐union tissue: current insights
Panteli, M., Pountos, I., Jones, E., & Giannoudis, P. V. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12532 · Cited by 127 · see citing works
“Cell senescence is known to play an important role in healing and tissue regeneration [60].”
BackgroundMolecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging
Neri, S., & Borzı̀, R. M. (2020) · Biomolecules · doi:10.3390/biom10020340 · Cited by 122 · see citing works
“DNA damage is one of the key drivers of aging and there is strong evidence that age-related accumulation of DNA damage in MSCs is partly responsible for age-related cellular dysfunctions [23].”
BackgroundInfluentialMuñoz‐Cánoves, P., Neves, J., & Sousa‐Victor, P. (2019) · FEBS Journal · doi:10.1111/febs.15182 · Cited by 111 · see citing works
“The accumulation of DNA damage is a potential source of genomic instability and an important contributor to global changes in the epigenome with aging [54, 55].”
BackgroundAtaxia-telangiectasia (A-T): An emerging dimension of premature ageing
Shiloh, Y., & Lederman, H. M. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.002 · Cited by 113 · see citing works
DNA damage and mitochondria in cancer and aging
Patel, J., Baptiste, B. A., Kim, E., Hussain, M., Croteau, D. L., & Bohr, V. A. (2020) · Carcinogenesis · doi:10.1093/carcin/bgaa114 · Cited by 106 · see citing works
Principles of the Molecular and Cellular Mechanisms of Aging
da Silva, P. F. L., & Schumacher, B. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.11.018 · Cited by 99 · see citing works
Self-citationHouck, A. L., Seddighi, S., & Driver, J. A. (2018) · Current Aging Science · doi:10.2174/1874609811666180223154436 · Cited by 95 · see citing works
“The decline in stem cells seems to be an integrative result of multiple types of damage to both cells and their microenvironment [31, 115].”
BackgroundGrigoriou, M., Banos, A., Filia, A., Pavlidis, P., Giannouli, S., Karali, V., Nikolopoulos, D., Pieta, A., Bertsias, G. K., Verginis, P., et al. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-215782 · Cited by 96 · see citing works
Siudeja, K., Nassari, S., Gervais, L., Skorski, P., Lameiras, S., Stolfa, D., Zande, M., Bernard, V., Frio, T. R., & Bardin, A. J. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.09.016 · Cited by 89 · see citing works
“During aging, defects in stem cell function contribute to a decline in renewal and repair of adult tissues (Behrens et al., 2014).”
Nonsense-mediated mRNA decay: a ‘nonsense’ pathway makes sense in stem cell biology
Han, X., Wei, Y., Wang, H., Wang, F., Ju, Z., & Li, T. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1272 · Cited by 91 · see citing works
Biological mechanisms of aging predict age‐related disease co‐occurrence in patients
Fraser, H. C., Kuan, V., Johnen, R., Zwierzyna, M., Hingorani, A. D., Beyer, A., & Partridge, L. (2022) · Aging Cell · doi:10.1111/acel.13524 · Cited by 91 · see citing works
Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells
Sousa‐Victor, P., Ayyaz, A., Hayashi, R., Qi, Y., Madden, D. T., Lunyak, V. V., & Jasper, H. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.059 · Cited by 90 · see citing works
“In vertebrate stem cell populations, such mechanisms include effective cell cycle checkpoints and DNA repair machineries (Behrens et al., 2014).”
BackgroundHämäläinen, R. H., Landoni, J. C., Ahlqvist, K. J., Goffart, S., Ryytty, S., Rahman, M. O., Brilhante, V., Icay, K., Hautaniemi, S., Wang, L., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0120-1 · Cited by 88 · see citing works
Aneuploidy causes premature differentiation of neural and intestinal stem cells
Gogendeau, D., Siudeja, K., Gambarotto, D., Pennetier, C., Bardin, A. J., & Basto, R. (2015) · Nature Communications · doi:10.1038/ncomms9894 · Cited by 87 · see citing works
Culberson, J. W., Kopel, J. J., Sehar, U., & Reddy, P. H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102001 · Cited by 88 · see citing works
Telomerase Is Essential for Zebrafish Heart Regeneration
Bednarek, D., González‐Rosa, J. M., Guzmán, G., Gutiérrez‐Gutiérrez, Ó., Aguado, T., Sánchez-Ferrer, C., Marques, I. J., Galardi‐Castilla, M., de Diego, I., Gómez, M. J., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.064 · Cited by 79 · see citing works
“The DNA damage response limits cellular proliferative capacity (Behrens et al., 2014).”
BackgroundMolecular and cellular mechanisms of aging in hematopoietic stem cells and their niches
Zhang, L., Mack, R. M., Breslin, P., & Zhang, J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00994-z · Cited by 78 · see citing works
Brosh, R. M., Bellani, M. A., Liu, Y., & Seidman, M. M. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.005 · Cited by 81 · see citing works
DNA Damage-Induced Inflammatory Microenvironment and Adult Stem Cell Response
Cinat, D., Coppes, R. P., & Barazzuol, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.729136 · Cited by 78 · see citing works
Panteli, M., Vun, J. S. H., Pountos, I., Howard, A. J., Jones, E., & Giannoudis, P. V. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17096 · Cited by 69 · see citing works
Mesenchymal Stem/Progenitor Cells: The Prospect of Human Clinical Translation
Rady, D., Abbass, M. M. S., El‐Rashidy, A. A., Moshy, S. E., Radwan, I. A., Dörfer, C. E., & El‐Sayed, K. M. F. (2020) · Stem Cells International · doi:10.1155/2020/8837654 · Cited by 68 · see citing works
De, S., Campbell, C., Venkitaraman, A. R., & Esposito, A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.074 · Cited by 67 · see citing works
“Such mechanisms are of central importance to understanding the complex response of multicellular tissues to DNA damage, which in turn underlies biological processes such as aging and carcinogenesis (Behrens et al., 2014; Ermolaeva et al., 2015).”
BackgroundStem cell aging in the skeletal muscle: The importance of communication
Hong, X., Campanario, S., Ramírez‐Pardo, I., Grima-Terrén, M., Isern, J., & Muñoz‐Cánoves, P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101528 · Cited by 69 · see citing works
Mitochondrial Stress Response in Neural Stem Cells Exposed to Electronic Cigarettes
Zahedi, A., Phandthong, R., Chaili, A., Leung, S., Omaiye, E. E., & Talbot, P. (2019) · iScience · doi:10.1016/j.isci.2019.05.034 · Cited by 64 · see citing works
Sun, J., Lo, H. T. J., Fan, L., Yiu, T. L., Shakoor, A., Li, G., Lee, W., & Sun, D. B. (2022) · Science Advances · doi:10.1126/sciadv.abp9245 · Cited by 62 · see citing works
“The findings are clinically important because genetic, morphological, and phenotypic changes in cell therapy products upon ex vivo expansion (52) and in stem cells isolated from aged donors (53) are not uncommon.”
BackgroundKhong, S. M. L., Lee, M. J., Kosaric, N., Khong, D., Dong, Y., Hopfner, Ú., Aitzetmüller, M. M., Duscher, D., Schäfer, R., & Gurtner, G. C. (2018) · Stem Cells · doi:10.1002/stem.2934 · Cited by 60 · see citing works
Loss of Slug Compromises DNA Damage Repair and Accelerates Stem Cell Aging in Mammary Epithelium
Gross, K. M., Zhou, W., Breindel, J. L., Ouyang, J., Jin, D. X., Sokol, E. S., Gupta, P. B., Huber, K., Zou, L., & Kuperwasser, C. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.043 · Cited by 58 · see citing works
Role of Mesenchymal Stem Cells in Counteracting Oxidative Stress—Related Neurodegeneration
Angeloni, C., Gatti, M., Prata, C., Hrelia, S., & Maraldi, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093299 · Cited by 57 · see citing works
Mechanisms of muscle cells alterations and regeneration decline during aging
Chinvattanachot, G., Rivas, D., & Duque, G. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102589 · Cited by 58 · see citing works
“As a result, the stem cell reservoir is compromised, and clonal selection is disrupted, further diminishing regenerative capacity (Behrens et al., 2014).”
DNA Damage Response in Hematopoietic Stem Cell Ageing
Li, T., Zhou, Z., Ju, Z., & Wang, Z. (2016) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.04.002 · Cited by 56 · see citing works
“concept that HSC ageing could be delayed or partially reversed by rejuvenating serum factors [69,91,92].”
BackgroundInfluentialTanaka, H., Goto, H., Inoko, A., Makihara, H., Enomoto, A., Horimoto, K., Matsuyama, M., Kurita, K., Izawa, I., & Inagaki, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.633891 · Cited by 55 · see citing works
“In this study, we have demonstrated that VIM mice exhibit subcutaneous fat loss and impaired wound healing, features of progeria (40, 41, 44).”
BackgroundRozhok, A. I., Salstrom, J. L., & DeGregori, J. V. (2014) · Aging · doi:10.18632/aging.100707 · Cited by 54 · see citing works
“Our results, thus, are concordant with other studies demonstrating the impact of aged tissue environments on stem cell fitness [67-70], and the importance of tissue microenvironment during tumor progression [22, 41-46].”
ResultDietary Regulation of Adult Stem Cells
Mana, M., Kuo, E. Y.-S., & Yilmaz, Ö. H. (2017) · Current Stem Cell Reports · doi:10.1007/s40778-017-0072-x · Cited by 55 · see citing works
Na, H., Akan, I., Abramowitz, L. K., & Hanover, J. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107632 · Cited by 53 · see citing works
Oxysterols are potential physiological regulators of ageing
de Médina, P., Silvente‐Poirot, S., & Poirot, M. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101615 · Cited by 51 · see citing works
Filia Is an ESC-Specific Regulator of DNA Damage Response and Safeguards Genomic Stability
Zhao, B., Zhang, W., Duan, Y.-L., Lu, Y., Cun, Y., Li, C., Guo, K., Nie, W., Li, L., Zhang, R., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.03.017 · Cited by 52 · see citing works
“DNA damage response (DDR) is a fundamental and evolutionarily conserved mechanism to preserve the genomic integrity of cells (Behrens et al., 2014; Jackson and Bartek, 2009).”
Hampel, H. J., Lista, S., Néri, C., & Vergallo, A. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101662 · Cited by 46 · see citing works
The increasing prevalence of cancer in the elderly: An investigation of epidemiological trends
Prathap, R., Kirubha, S., Rajan, A. T., Manoharan, S., & Elumalai, K. (2024) · Aging Medicine · doi:10.1002/agm2.12347 · Cited by 45 · see citing works
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“[159]”
Chua, H. L., Plett, P. A., Fisher, A., Sampson, C. H., Vemula, S., Feng, H., Sellamuthu, R., Wu, T., MacVittie, T. J., & Orschell, C. M. (2019) · Health Physics · doi:10.1097/hp.0000000000000950 · Cited by 45 · see citing works
“3 also illustrates the loss in engraftment potential of HSC from naïve NI mice that occurred naturally with aging (Morrison et al. 1996; Kim et al. 2003; Kamminga et al. 2005; Nijnik et al. 2007; Rossi et al. 2007; Rube et al. 2011; Snoeck 2013; Behrens et al. 2014).”
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Impact of stress on aged immune system compartments: Overview from fundamental to clinical data
Fali, T., Vallet, H., & Sauce, D. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.02.007 · Cited by 43 · see citing works
“Nowadays, there are several postulates of stem cell aging: DNA damage due to ROS accumulation along with a decline in the activity of DNA repair gene expression and error accumulation in genetic material is always a problem for systems regardless of the age (Behrens et al., 2014).”
BackgroundPatient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy
Schimke, M., Marozin, S., & Lepperdinger, G. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00362 · Cited by 42 · see citing works
“MSC derived from old patients exhibit reduced proliferative capacity and in some cases show skewed multilineage differentiation potentials, telomere shortening, or DNA damage accumulation (Behrens et al., 2014; Efimenko et al., 2014; Kizilay Mancini et al., 2015; Reitinger et al., 2015).”
BackgroundKim, J. Y., Ohn, J., Yoon, J.-S., Kang, B. M., Park, M., Kim, S., Lee, W., Hwang, S., Kim, J., Kim, K. H., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11665-0 · Cited by 41 · see citing works
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The Role of Aging in Idiopathic Pulmonary Fibrosis
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“result in a decline in cell function, polypeptide malformation, or even the generation of malignant cells [20].”
BackgroundBronchioalveolar stem cells in lung repair, regeneration and disease
Jones, B., & Starkey, M. R. (2020) · The Journal of Pathology · doi:10.1002/path.5527 · Cited by 38 · see citing works
“In chronic respiratory diseases, or following lung damage, these cells could be lost, limiting their ability to promote lung regeneration and repair [44,45].”
BackgroundInfluentialTemporal activation of XRCC1-mediated DNA repair is essential for muscle differentiation
Al-Khalaf, M. H., Blake, L. E., Larsen, B. D., Bell, R. A. V., Brunette, S., Parks, R. J., Rudnicki, M. A., McKinnon, P. J., Dilworth, F. J., & Megeney, L. A. (2016) · Cell Discovery · doi:10.1038/celldisc.2015.41 · Cited by 34 · see citing works
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“It is now known that stem cell functionality decreases during aging contributing to age-associated pathologies and the overall aging process of the organism (Behrens et al., 2014).”
DNA damage accumulation during fractionated low-dose radiation compromises hippocampal neurogenesis
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“Radiation-induced accumulation of DNA damage in neuronal stem/progenitor cells may have profound impact on genomic integrity and may contribute to impairment of stem cell functions, with loss of selfrenewal and differentiation capacities [20,21].”
BackgroundDNA repair and mutations during quiescence in yeast
Gangloff, S., & Arcangioli, B. (2017) · FEMS Yeast Research · doi:10.1093/femsyr/fox002 · Cited by 33 · see citing works
“Indeed, in response to excessive DNA damage or mutations, post-mitotic cells activate a cell death program that reduces the window for molecular genetic studies (Behrens et al. 2014).”
BackgroundFine-tuning the ubiquitin code at DNA double-strand breaks: deubiquitinating enzymes at work
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“REVIEW published: 08 September 2015 doi: 10.3389/fgene.2015.00282 Edited by: Alessandra Montecucco,”
BackgroundInfluentialWnt-Responsive Stem Cell Fates in the Oral Mucosa
Yuan, X., Xu, Q., Zhang, X., Brunt, L. A. V., Ticha, P., & Helms, J. A. (2019) · iScience · doi:10.1016/j.isci.2019.10.016 · Cited by 31 · see citing works
“Most cancers arise from the accumulation of DNA mutations due to infidelity of the DNA replication and failure of DNA repair (Behrens et al., 2014; Vassilev and DePamphilis, 2017) and the risk of a stem cell undergoing oncogenic transformation is strongly correlated with the total number of divisions it undergoes (Tom…”
BackgroundSave your gut save your age: The role of the microbiome in stem cell ageing
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“Decline in stem cell regeneration is considered as a marker of aging since the proportion of stem cells and their pace of division gradually decreases over time (55).”
BackgroundAGO2 silences mobile transposons in the nucleus of quiescent cells
Sala, L., Kumar, M., Prajapat, M. K., Chandrasekhar, S., Cosby, R. L., Rocca, G. L., Macfarlan, T. S., Awasthi, P., Chari, R., Kruhlak, M. J., et al. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-01151-z · Cited by 30 · see citing works
“The long-lived nature of quiescent cells poses a risk to the organism because mutations that impact their functions can lead to both impaired tissue maintenance and tumorigenesis 47 .”
Xavier, J. M., Morgado, A. L., Rodrigues, C. M., & Solá, S. (2014) · Cell Cycle · doi:10.4161/15384101.2014.962951 · Cited by 30 · see citing works
Transcription-associated events affecting genomic integrity
Sebastian, R., & Oberdoerffer, P. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0288 · Cited by 28 · see citing works
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“…with age, as we (Chua et al. 2019) and others (Rossi et al. 2005) have reported, despite declining functional potential (Morrison et al. 1996; Kim et al. 2003; Kamminga et al. 2005; Nijnik et al. 2007; Rossi et al. 2007; Rube et al. 2011; Chua et al. 2012, 2019; Snoeck 2013; Behrens et al. 2014).”
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Dissection of the Cord Blood Stromal Component Reveals Predictive Parameters for Culture Outcome
Barilani, M., Lavazza, C., Viganò, M., Montemurro, T., Boldrin, V., Parazzi, V., Montelatici, E., Crosti, M., Moro, M., Giordano, R., et al. (2014) · Stem Cells and Development · doi:10.1089/scd.2014.0160 · Cited by 28 · see citing works
“In fact, the aging process is characterized by impaired regenerative capabilities and it has been proposed that this is also related to less effective or absent adult stem cell functionalities [44,45].”
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BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress
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Genomic Instability in Stem Cells: The Basic Issues
González, E. A. P., & Haider, K. H. (2021) · Springer eBooks · doi:10.1007/978-981-16-0301-3_5 · Cited by 27 · see citing works
Aging: A cell source limiting factor in tissue engineering
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- Authors
- Behrens, A., van Deursen, J. M., Rudolph, K. L., & Schumacher, B.
- Affiliations
- King's College London (GB)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- University of Cologne (DE)
- Corresponding author
- Behrens, Axel
- Rudolph, K. Lenhard
- Schumacher, Björn
- Venue
- Nature Cell Biology
- Published
- 2014-02-28
- Volume
- 16
- Issue
- 3
- Pages
- 201-207
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4214082
- OpenAlex
- W2054525725
- Cited by
- 207
- References
- 98
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 11 · 2023: 12 · 2022: 10 · 2021: 17 · 2020: 19 · 2019: 27 · 2018: 13 · 2017: 18 · 2016: 20 · 2015: 32 · 2014: 13
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Cancer Research UK (15679)
- National Cancer Institute (R01CA126828)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- 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
- Keywords
- genomic instability, aging, stem cell function, DNA damage, stem cell niche, tissue maintenance, tissue repair, carcinogenesis
- MeSH terms
- Aneuploidy, Animals, Cells, Cultured, DNA Damage, DNA Repair, Humans, Neoplasms, Genome, Human, Cellular Senescence, Adult Stem Cells
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