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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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“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
A C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
Rejuvenation of aged progenitor cells by exposure to a young systemic environment
Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005) · Nature · doi:10.1038/nature03260 · Cited by 2,287
IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P. C., Cervera, P., & Le Bouc, Y. (2003) · Nature · doi:10.1038/nature01298 · Cited by 2,109
Causes and consequences of replication stress
Zeman, M. K., & Cimprich, K. A. (2014) · Nature Cell Biology · doi:10.1038/ncb2897 · Cited by 2,079
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951
ATR: an essential regulator of genome integrity
Cimprich, K. A., & Cortez, D. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2450 · Cited by 1,798
Research works printed but not linked: 1
- Krishnamurthy, J. et al. Ink4a/Arf expression is a biomarker of aging. J. Clin. Invest. 114, 1299–1307 (2004). · DOI · Paper page
Cited by
Sorted by citations
Inflammation, fracture and bone repair
Loi, F., Córdova, L. A., Pajarinen, J., Lin, T., Yao, Z., & Goodman, S. B. (2016) · Bone · doi:10.1016/j.bone.2016.02.020 · Cited by 1,339
“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 1,031
“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 892
Stem cell aging: mechanisms, regulators and therapeutic opportunities
Oh, J., Lee, Y. D., & Wagers, A. J. (2014) · Nature Medicine · doi:10.1038/nm.3651 · Cited by 796
The effects of aging in the hippocampus and cognitive decline
Bettio, L. E. B., Rajendran, L., & Gil‐Mohapel, J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.04.030 · Cited by 700
“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
“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
“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
Self-citationVitale, I., Manic, G., De Maria, R., Kroemer, G., & Galluzzi, L. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.04.006 · Cited by 361
“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
“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
Meiners, S., Eickelberg, O., & Königshoff, M. (2015) · European Respiratory Journal · doi:10.1183/09031936.00186914 · Cited by 340
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
Self-citationSenescence in COPD and Its Comorbidities
Barnes, P. J. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034314 · Cited by 278
Schwartz, S. D., Tan, G. S. W., Hosseini, H., & Nagiel, A. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18681 · Cited by 253
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 236
Mechanisms of development of multimorbidity in the elderly
Barnes, P. J. (2015) · European Respiratory Journal · doi:10.1183/09031936.00229714 · Cited by 204
Neri, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102406 · Cited by 195
“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 206
Epigenetic Control of Stem Cell Potential during Homeostasis, Aging, and Disease
Beerman, I., & Rossi, D. J. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.05.009 · Cited by 182
“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 182
“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
FOXM1: A key oncofoetal transcription factor in health and disease
Bella, L., Zona, S., de Moraes, G. N., & Lam, E. W. ‐. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.07.008 · Cited by 167
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 184
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
“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 178
“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
“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 165
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 147
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
Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging
Li, X., Wang, J., Wang, L., Gao, Y., Feng, G., Li, G., Zou, J., Yu, M., Li, Y. F., Liu, C., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00964-6 · Cited by 143
“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
“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., & Borzì, R. M. (2020) · Biomolecules · doi:10.3390/biom10020340 · Cited by 126
“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 117
“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 115
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 109
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 106
Self-citationHouck, A. L., Seddighi, S., & Driver, J. A. (2018) · Current Aging Science · doi:10.2174/1874609811666180223154436 · Cited by 96
“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 99
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 93
“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
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 90
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 92
“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 89
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 84
Culberson, J. W., Kopel, J. J., Sehar, U., & Reddy, P. H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102001 · Cited by 95
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 84
“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 80
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 84
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 79
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
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 69
De, S., Campbell, C., Venkitaraman, A. R., & Esposito, A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.074 · Cited by 67
“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 73
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
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
“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 59
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
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 62
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 61
“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
“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 56
“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 56
“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 57
Na, H., Akan, I., Abramowitz, L. K., & Hanover, J. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107632 · Cited by 53
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de Médina, P., Silvente‐Poirot, S., & Poirot, M. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101615 · Cited by 55
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 53
“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 47
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
Morfeld, P., Bruch, J., Levy, L., Ngiewih, Y., Chaudhuri, I. S., Muranko, H. J., Myerson, R., & McCunney, R. J. (2015) · Particle and Fibre Toxicology · doi:10.1186/s12989-015-0079-3 · Cited by 45
“[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 46
“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).”
Ichijo, R., Maki, K., Kabata, M., Murata, T., Nagasaka, A., Ishihara, S., Haga, H., Honda, T., ADACHI, T., Yamamoto, T., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00244-6 · Cited by 44
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 46
“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
“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 42
Fernung, L. P., Yang, Q., Sakamuro, D., Kumari, A., Mas, A., & Al-Hendy, A. A. (2018) · Biology of Reproduction · doi:10.1093/biolre/ioy097 · Cited by 39
The Role of Aging in Idiopathic Pulmonary Fibrosis
Leung, J., Cho, Y. S., Lockey, R. F., & Kolliputi, N. (2015) · Lung · doi:10.1007/s00408-015-9729-3 · Cited by 38
“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 41
“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
Barnes, P. J. (2019) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-3681-2_3 · Cited by 37
Iglesias, M., Felix, D. A., Gutiérrez‐Gutiérrez, Ó., Miguel-Bonet, M. D. M. D., Sahu, S., Fernández-Varas, B., Perona, R., Aboobaker, A. A., Flores, I., & González‐Estévez, C. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2019.06.005 · Cited by 39
“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
Schmal, Z., Isermann, A., Hladik, D., von Toerne, C., Tapio, S., & Rübe, C. E. (2019) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2019.04.021 · Cited by 35
“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 35
“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
Citterio, E. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00282 · Cited by 30
“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
“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
Tan, Y. J., Wei, Z., Chen, J., An, J., Li, M., Zhou, L., Men, Y., & Zhao, S. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14373 · Cited by 32
Saha, P., Ajgaonkar, S., Maniar, D., Sahare, S., Mehta, D. S., & Nair, S. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1370951 · Cited by 29
“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
“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
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
Wu, T., Plett, P. A., Chua, H. L., Jacobsen, M. H., Sandusky, G. E., MacVittie, T. J., & Orschell, C. M. (2020) · Health Physics · doi:10.1097/hp.0000000000001352 · Cited by 31
“…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).”
BackgroundHe, J., Zang, S., Liu, N., Ji, M., Ma, D., & Ji, C. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.109908 · Cited by 28
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
“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].”
Mancini, A., Vitucci, D., Labruna, G., Imperlini, E., Randers, M. B., Schmidt, J. F., Hagman, M., Andersen, T. R., Russo, R., Orrù, S., et al. (2017) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3562-8 · Cited by 28
BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress
Vasudevarao, M. D., Pena, D. P., Ihle, M., Bongiovanni, C., Maity, P., Geissler, D., Mohammadi, H. F., Rall-Scharpf, M., Niemann, J., Mommersteeg, M. T. M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56993-6 · Cited by 26
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
Aging: A cell source limiting factor in tissue engineering
Khorraminejad‐Shirazi, M., Dorvash, M., Estedlal, A., Hoveidaei, A. H., Mazloomrezaei, M., & Mosaddeghi, P. (2019) · World Journal of Stem Cells · doi:10.4252/wjsc.v11.i10.787 · Cited by 28
Lin, X., Li, Y., Gong, L., Yun, J. H., Xu, S., Tesfaigzi, Y., Qiao, D., & Zhou, X. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103463 · Cited by 24
Squillaro, T., Antonucci, I., Alessio, N., Esposito, A. A., Cipollaro, M., Melone, M. A. B., Peluso, G., Stuppia, L., & Galderisi, U. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25807 · Cited by 25
Poisa-Beiro, L., Thoma, J., Landry, J., Sauer, S., Yamamoto, A., Eckstein, V., Romanov, N., Raffel, S., Hoffmann, G. F., Bork, P., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-68396-2 · Cited by 23
Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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