The DOI matches its Crossref record; 258 of the 258 references it cites were found in a registry or an index.
Cellular and epigenetic drivers of stem cell ageing
Abstract
Adult tissue stem cells have a pivotal role in tissue maintenance and regeneration throughout the lifespan of multicellular organisms. Loss of tissue homeostasis during post-reproductive lifespan is caused, at least in part, by a decline in stem cell function and is associated with an increased incidence of diseases. Hallmarks of ageing include the accumulation of molecular damage, failure of quality control systems, metabolic changes and alterations in epigenome stability. In this Review, we discuss recent evidence in support of a novel concept whereby cell-intrinsic damage that accumulates during ageing and cell-extrinsic changes in ageing stem cell niches and the blood result in modifications of the stem cell epigenome. These cumulative epigenetic alterations in stem cells might be the cause of the deregulation of developmental pathways seen during ageing. In turn, they could confer a selective advantage to mutant and epigenetically drifted stem cells with altered self-renewal and functions, which contribute to the development of ageing-associated organ dysfunction and disease.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“The exact mechanism for decreased stem and progenitor cell capacity to rejuvenate is not known, but the common mechanisms of stem cell aging can be explained by some cell-intrinsic and extrinsic factors including telomere attrition, molecular damage, epigenetic drift and deregulation of developmental pathways”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Ermolaeva et al. 2018
Citations
Cites
Items 201–258 of 258
H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cellsPreprint
Fernandez-Fernandez, A., Bayón, G. F., Urdinguio, R. G., Toraño, E. G., García, M. G., Carella, A., Petrus-Reurer, S., Ferrero, C., Martinez-Camblor, P., Cubillo, I., et al. (2014) · Genome Research · doi:10.1101/gr.169011.113 · Cited by 140
Vitamin C in Stem Cell Biology: Impact on Extracellular Matrix Homeostasis and Epigenetics
D’Aniello, C., Cermola, F., Patriarca, E. J., & Minchiotti, G. (2017) · Stem Cells International · doi:10.1155/2017/8936156 · Cited by 135
Tang, D., Tao, S., Chen, Z., Koliesnik, I. O., Calmes, P. G., Hoerr, V., Han, B., Gebert, N., Zörnig, M., Löffler, B., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151100 · Cited by 133
Self-citationEpigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals
Schwörer, S., Becker, F., Feller, C., Baig, A. H., Köber, U., Henze, H., Kraus, J. M., Xin, B., Lechel, A., Lipka, D. B., et al. (2016) · Nature · doi:10.1038/nature20603 · Cited by 132
Self-citationO-GlcNAcylation Prevents Aggregation of the Polycomb Group Repressor Polyhomeotic
Gambetta, M. C., & Müller, J. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.10.020 · Cited by 124
Kaaij, L. J. T., van de Wetering, M., Fang, F., Decato, B. E., Molaro, A., van de Werken, H. J. G., van Es, J. H., Schuijers, J., de Wit, E., de Laat, W. L., et al. (2013) · Genome biology · doi:10.1186/gb-2013-14-5-r50 · Cited by 118
Goldberg, E. L., Romero-Aleshire, M. J., Renkema, K. R., Ventevogel, M. S., Chew, W. M., Uhrlaub, J. L., Smithey, M. J., Limesand, K. H., Sempowski, G. D., Brooks, H. L., et al. (2014) · Aging Cell · doi:10.1111/acel.12280 · Cited by 107
Chaperones convert the energy from ATP into the nonequilibrium stabilization of native proteins
Goloubinoff, P., Sassi, A. S., Fauvet, B., Barducci, A., & Rios, P. D. L. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0013-8 · Cited by 106
Methylation reveals a niche: stem cell succession in human colon crypts
Kim, K., & Shibata, D. K. (2002) · Oncogene · doi:10.1038/sj.onc.1205604 · Cited by 104
Histone exchange and histone modifications during transcription and aging
Das, C., & Tyler, J. K. (2011) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2011.08.001 · Cited by 103
Wang, L., Ryoo, H. D., Qi, Y., & Jasper, H. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005220 · Cited by 102
Wnt activity and basal niche position sensitize intestinal stem and progenitor cells to DNA damage
Tao, S., Tang, D., Morita, Y., Sperka, T., Omrani, O., Lechel, A., Sakk, V., Kraus, J. M., Kestler, H. A., Kühl, M., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490700 · Cited by 98
Self-citationKirschner, K., Chandra, T., Kiselev, V. Y., Cruz, D. F. S., Macaulay, I. C., Park, H. J., Li, J., Kent, D. G., Kumar, R., Pask, D. C., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.074 · Cited by 97
Park, J., Kim, Y.-S., & Yoo, M. (2009) · Aging · doi:10.18632/aging.100054 · Cited by 96
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
The asymmetric segregation of damaged proteins is stem cell–type dependent
Bufalino, M. R., DeVeale, B., & van der Kooy, D. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201207052 · Cited by 92
Sex hormones establish a reserve pool of adult muscle stem cells
Kim, J., Han, G.-C., Seo, J.-Y., Park, I., Park, W., Jeong, H., Lee, S. H., Bae, S.-H., Seong, J., Yum, M. K., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3401 · Cited by 91
Telomerase abrogates aneuploidy‐induced telomere replication stress, senescence and cell depletion
Meena, J. K., Cerutti, A., Beichler, C., Morita, Y., Bruhn, C., Kumar, M., Kraus, J. M., Speicher, M. R., Wang, Z., Kestler, H. A., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490070 · Cited by 87
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
Noormohammadi, A., Khodakarami, A., Gutiérrez-García, R., Lee, H. J., Koyuncu, S., König, T., Schindler, C., Sáez, I., Fatima, A., Dieterich, C., et al. (2016) · Nature Communications · doi:10.1038/ncomms13649 · Cited by 86
Kazakevych, J., Sayols, S., Messner, B., Krienke, C., & Soshnikova, N. V. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx167 · Cited by 85
Scourzic, L., Couronné, L., Pedersen, M. T., Della-Valle, V., Diop, M. K., Mylonas, E., Calvo, J., Mouly, E., Lopez, C. K., Martin, N., et al. (2016) · Leukemia · doi:10.1038/leu.2016.29 · Cited by 84
Non-canonical functions of the DNA methylome in gene regulation
Reddington, J. P., Pennings, S., & Meehan, R. R. (2013) · Biochemical Journal · doi:10.1042/bj20121585 · Cited by 81
Nuschke, A., Rodrigues, M., Wells, A. W., Sylakowski, K., & Wells, A. H. (2016) · Stem Cell Research & Therapy · doi:10.1186/s13287-016-0436-7 · Cited by 81
Mian, S. A., Smith, A., Kulasekararaj, A. G., Kizilors, A., Mohamedali, A. M., Lea, N. C., Mitsopoulos, C., Ford, K., Nasser, E. E., Seidl, T., et al. (2013) · Haematologica · doi:10.3324/haematol.2012.075325 · Cited by 77
Ageing as developmental decay: insights from p16INK4a.
Martin, N., Beach, D., & Gil, J. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.09.008 · Cited by 76
Regulation of Embryonic Stem Cell Pluripotency by Heat Shock Protein 90
Bradley, E., Bieberich, E., Mivechi, N. F., Tangpisuthipongsa, D., & Wang, G. (2012) · Stem Cells · doi:10.1002/stem.1143 · Cited by 75
Age-related human small intestine methylation: evidence for stem cell niches
Kim, J. Y., Siegmund, K. D., Tavaré, S., & Shibata, D. K. (2005) · BMC Medicine · doi:10.1186/1741-7015-3-10 · Cited by 73
Hsieh, J. C. F., Berg, D. V. D., Kang, H., Hsieh, C., & Lieber, M. R. (2013) · Aging Cell · doi:10.1111/acel.12053 · Cited by 71
A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability
Fusco, S., Leone, L., Barbati, S. A., Samengo, D., Piacentini, R., Maulucci, G., Toietta, G., Spinelli, M., McBurney, M. W., Pani, G., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.092 · Cited by 71
Wnt5a Regulates Hematopoietic Stem Cell Proliferation and Repopulation Through the Ryk Receptor
Povinelli, B. J., & Nemeth, M. J. (2013) · Stem Cells · doi:10.1002/stem.1513 · Cited by 67
The Janus face of DNA methylation in aging
Mugatroyd, C., Wu, Y., Bockmühl, Y., & Spengler, D. (2010) · Aging · doi:10.18632/aging.100124 · Cited by 66
Small Bowel Enterocyte Apoptosis and Proliferation Are Increased in the Elderly
Ciccocioppo, R., Sabatino, A. D., Luinetti, O., Rossi, M., Cifone, M., & Corazza, G. (2002) · Gerontology · doi:10.1159/000058351 · Cited by 64
Kauppinen, T. M., Gan, L., & Swanson, R. A. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.04.005 · Cited by 64
p53 induces distinct epigenetic states at its direct target promoters
Vrba, L., Junk, D. J., Novák, P., & Futscher, B. W. (2008) · BMC Genomics · doi:10.1186/1471-2164-9-486 · Cited by 60
What have we learned on aging from omics studies?
Cellerino, A., & Ori, A. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.06.012 · Cited by 59
Self-citationThe Cancer Epigenome: Its Origins, Contributions to Tumorigenesis, and Translational Implications
Baylin, S. B. (2012) · Proceedings of the American Thoracic Society · doi:10.1513/pats.201201-001ms · Cited by 55
Discrete roles of canonical and non-canonical Wnt signaling in hematopoiesis and lymphopoiesis
Famili, F., Naber, B. A. E., Vloemans, S. A., de Haas, E. F. E., Tiemessen, M. M., & Staal, F. J. T. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.326 · Cited by 55
Genome instability of ageing stem cells—Induction and defence mechanisms
Burkhalter, M. D., Rudolph, K. L., & Sperka, T. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.004 · Cited by 54
Self-citationVidrich, A., Buzan, J. M., Brodrick, B., Ilo, C., Bradley, L., Fendig, K. S., Sturgill, T., & Cohn, S. M. (2009) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.90589.2008 · Cited by 54
Regulation of histone modifying enzymes by the ubiquitin–proteasome system
Zou, C., & Mallampalli, R. K. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.12.016 · Cited by 53
Ro, S. W., & Rannala, B. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201405498 · Cited by 52
Missios, P., Zhou, Y., Guachalla, L. M., von Figura, G., Wegner, A., Chakkarappan, S. R., Binz, T. M., Gompf, A., Hartleben, G., Burkhalter, M. D., et al. (2014) · Nature Communications · doi:10.1038/ncomms5924 · Cited by 49
Self-citationDietary restriction enhances germline stem cell maintenance
Mair, W. B., McLeod, C. J., Wang, L., & Jones, D. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00602.x · Cited by 47
Berent-Maoz, B., Montecino-Rodriguez, E., Signer, R. A. J., & Dorshkind, K. (2012) · Blood · doi:10.1182/blood-2011-12-400002 · Cited by 46
Cairney, C. J., Sanguinetti, G., Ranghini, E. J., Chantry, A., Nostro, M. C., Bhattacharyya, A., Svendsen, C. N., Keith, W. N., & Bellantuono, I. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.01.015 · Cited by 43
A Notch positive feedback in the intestinal stem cell niche is essential for stem cell self‐renewal
Chen, K., Srinivasan, T., Tung, K., Belmonte, J. M., Wang, L., Murthy, P. K. L., Choi, J., Rakhilin, N., King, S., Varanko, A. K., et al. (2017) · Molecular Systems Biology · doi:10.15252/msb.20167324 · Cited by 43
Alam, D. A., Danopoulos, S., Schall, K. A., Sala, F. G., Almohazey, D., Fernández, G. E., Georgia, S. K., Frey, M. R., Ford, H. R., Grikscheit, T. C., et al. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00158.2014 · Cited by 42
Proliferating cell nuclear antigen expression is increased in small bowel epithelium in the elderly
Corazza, G. R., Ginaldi, L., Quaglione, G. R., Ponzielli, F., Vecchio, L., Biagi, F., & Quaglino, D. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00044-x · Cited by 39
Blocking promiscuous activation at cryptic promoters directs cell type–specific gene expression
Kim, J., Lu, C., Srinivasan, S., Awe, S., Brehm, A., & Fuller, M. T. (2017) · Science · doi:10.1126/science.aal3096 · Cited by 39
Hormonal Control of Stem Cell Systems
Gancz, D., & Gilboa, L. (2013) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101512-122331 · Cited by 37
Lifelong dietary intervention does not affect hematopoietic stem cell function
Lazare, S., Ausema, A., Reijne, A. C., van Dijk, G., van Os, R. P., & de Haan, G. (2017) · Experimental Hematology · doi:10.1016/j.exphem.2017.06.002 · Cited by 36
Song, Z., Zhang, J., Ju, Z., & Rudolph, K. L. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00802.x · Cited by 36
Self-citationArai, K., Buonamici, S., Chan, B., Corson, L., Endo, A., Gerard, B., Hao, M., Karr, C. D., Kira, K., Lee, L., et al. (2014) · Organic Letters · doi:10.1021/ol502556c · Cited by 23
Janus Kinase 2: An Epigenetic 'Writer' that Activates Leukemogenic Genes
He, J., & Zhang, Y. (2010) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjp054 · Cited by 11
Identification of Aging-Associated Gene Expression Signatures That Precede Intestinal Tumorigenesis
Okuchi, Y., Imajo, M., Mizuno, R., Kamioka, Y., Miyoshi, H., Taketo, M. M., Nagayama, S., Sakai, Y., & Matsuda, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162300 · Cited by 9
Liu, D.-W., Tsai, S.-M., Lin, B.-F., Jiang, Y., & Wang, W.-P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058310 · Cited by 6
Cited by
Sorted by citations
Benefits of Metformin in Attenuating the Hallmarks of Aging
Kulkarni, A. S., Gubbi, S., & Barzilai, N. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.04.001 · Cited by 766
Mechanisms underlying T cell ageing
Goronzy, J. J., & Weyand, C. M. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0180-1 · Cited by 506
Padeken, J., Methot, S. P., & Gasser, S. M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00483-w · Cited by 532
The ageing epigenome and its rejuvenation
Zhang, W., Qu, J., Liu, G.-H., & Belmonte, J. C. I. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0204-5 · Cited by 458
mTOR as a central regulator of lifespan and aging
Papadopoli, D. J., Boulay, K., Kazak, L., Pollak, M., Mallette, F. A., Topisirović, I., & Hulea, L. (2019) · F1000Research · doi:10.12688/f1000research.17196.1 · Cited by 447
Metadata
- Authors
- Ermolaeva, M., Neri, F., Ori, A., & Rudolph, K. L.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Corresponding author
- Ermolaeva, Maria
- Neri, Francesco
- Rudolph, K. Lenhard
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2018-06-01
- Volume
- 19
- Issue
- 9
- Pages
- 594-610
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2805636495
- Semantic Scholar
- 422884d09599558429d720d9e413dadf9c506510
- Cited by
- 272
- References
- 258
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 37 · 2023: 42 · 2022: 33 · 2021: 49 · 2020: 33 · 2019: 27 · 2018: 5
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- stem cell aging, epigenetic drift, stem cell niche, tissue homeostasis, age-related diseases, stem cell self-renewal, organ dysfunction
- MeSH terms
- Animals, Homeostasis, Humans, Stem Cells, Cellular Senescence, Epigenesis, Genetic, Epigenomics
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
