{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:04:47Z","timestamp":1793127887526,"version":"4.5.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Aging"],"DOI":"10.1038\/s43587-026-01136-9","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T09:51:52Z","timestamp":1782813112000},"page":"1377-1394","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Therapeutic inhibition of telomeric DNA damage response rescues hematopoietic dysfunction driven by telomere shortening and aging"],"prefix":"10.1038","volume":"6","author":[{"given":"Alessia","family":"Oppezzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9884-9189","authenticated-orcid":false,"given":"Sara","family":"Sepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Cicio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Cancila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Sasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Marinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Cabrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Pallavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Iacomino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Simoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2181-4243","authenticated-orcid":false,"given":"Dmitrii","family":"Malyshev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Boggio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"di Lillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Rosso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Tavella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-3854","authenticated-orcid":false,"given":"Lucrezia A.","family":"Trastus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Rossiello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Roscia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Cantaloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Manenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-1524","authenticated-orcid":false,"given":"Paola","family":"Cavalcante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Giuseppe","family":"Pelicci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0639-8238","authenticated-orcid":false,"given":"Raffaella","family":"Di Micco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Nicosia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Tripodo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9603-5966","authenticated-orcid":false,"given":"Fabrizio","family":"d\u2019Adda di Fagagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"1136_CR1","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nrm2848","volume":"11","author":"RJ O\u2019Sullivan","year":"2010","unstructured":"O\u2019Sullivan, R. J. & Karlseder, J. Telomeres: protecting chromosomes against genome instability. Nat. Rev. Mol. Cell Biol. 11, 171\u2013181 (2010).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1136_CR2","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/345458a0","volume":"345","author":"CW Greidert","year":"1990","unstructured":"Greidert, C. W., Harley, C. B. & Futcher, A. B. Telomeres shorten during ageing of human fibroblasts. Nature 345, 458\u2013460 (1990).","journal-title":"Nature"},{"key":"1136_CR3","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1101\/gad.2021311","volume":"25","author":"SE Polo","year":"2011","unstructured":"Polo, S. E. & Jackson, S. P. Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev. 25, 409\u2013433 (2011).","journal-title":"Genes Dev."},{"key":"1136_CR4","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nature02118","volume":"426","author":"F D\u2019Adda Di Fagagna","year":"2003","unstructured":"D\u2019Adda Di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194\u2013198 (2003).","journal-title":"Nature"},{"key":"1136_CR5","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.gde.2014.06.009","volume":"26","author":"F Rossiello","year":"2014","unstructured":"Rossiello, F., Herbig, U., Longhese, M. P., Fumagalli, M. & d\u2019Adda di Fagagna, F. Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing. Curr. Opin. Genet. Dev. 26, 89\u201395 (2014).","journal-title":"Curr. Opin. Genet. Dev."},{"key":"1136_CR6","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","volume":"22","author":"R Di Micco","year":"2021","unstructured":"Di Micco, R., Krizhanovsky, V., Baker, D. & d\u2019Adda di Fagagna, F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell Biol. 22, 75\u201395 (2021).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1136_CR7","doi-asserted-by":"crossref","unstructured":"Rossiello, F. et al. DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs. Nat. Commun. 8, 13980 (2017).","DOI":"10.1038\/ncomms13980"},{"key":"1136_CR8","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nature11179","volume":"488","author":"S Francia","year":"2012","unstructured":"Francia, S. et al. Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature 488, 231\u2013235 (2012).","journal-title":"Nature"},{"key":"1136_CR9","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1038\/ncb3643","volume":"19","author":"F Michelini","year":"2017","unstructured":"Michelini, F. et al. Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks. Nat. Cell Biol. 19, 1400\u20131411 (2017).","journal-title":"Nat. Cell Biol."},{"key":"1136_CR10","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1242\/jcs.182188","volume":"129","author":"S Francia","year":"2016","unstructured":"Francia, S., Cabrini, M., Matti, V., Oldani, A. & d\u2019Adda di Fagagna, F. DICER, DROSHA and DNA damage response RNAs are necessary for the secondary recruitment of DNA damage response factors. J. Cell Sci. 129, 1468\u20131476 (2016).","journal-title":"J. Cell Sci."},{"key":"1136_CR11","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1038\/s41556-019-0392-4","volume":"21","author":"F Pessina","year":"2019","unstructured":"Pessina, F. et al. Functional transcription promoters at DNA double-strand breaks mediate RNA-driven phase separation of damage-response factors. Nat. Cell Biol. 21, 1286\u20131299 (2019).","journal-title":"Nat. Cell Biol."},{"key":"1136_CR12","doi-asserted-by":"publisher","first-page":"4990","DOI":"10.1038\/s41467-019-13018-3","volume":"10","author":"J Aguado","year":"2019","unstructured":"Aguado, J. et al. Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson\u2013Gilford progeria syndrome. Nat. Commun. 10, 4990 (2019).","journal-title":"Nat. Commun."},{"key":"1136_CR13","doi-asserted-by":"publisher","first-page":"e53658","DOI":"10.15252\/embr.202153658","volume":"23","author":"S Sepe","year":"2022","unstructured":"Sepe, S. et al. DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging. EMBO Rep. 23, e53658 (2022).","journal-title":"EMBO Rep."},{"key":"1136_CR14","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1146\/annurev-genom-010422-091101","volume":"23","author":"M Armanios","year":"2022","unstructured":"Armanios, M. The role of telomeres in human disease. Annu. Rev. Genomics Hum. Genet. 23, 363\u2013381 (2022).","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"1136_CR15","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41556-022-00842-x","volume":"24","author":"F Rossiello","year":"2022","unstructured":"Rossiello, F., Jurk, D., Passos, J. F. & d\u2019Adda di Fagagna, F. Telomere dysfunction in ageing and age-related diseases. Nat. Cell Biol. 24, 135\u2013147 (2022).","journal-title":"Nat. Cell Biol."},{"key":"1136_CR16","doi-asserted-by":"publisher","first-page":"1167848","DOI":"10.3389\/fonc.2023.1167848","volume":"13","author":"K Roka","year":"2023","unstructured":"Roka, K., Solomou, E. E. & Kattamis, A. Telomere biology: from disorders to hematological diseases. Front. Oncol. 13, 1167848 (2023).","journal-title":"Front. Oncol."},{"key":"1136_CR17","doi-asserted-by":"crossref","unstructured":"Schuck, P. L., Ackerson, S. M. & Stewart, J. A. in Encyclopedia of Cell Biology 2nd edn, Vol. 1 (ed Raben, D. M.) 523\u2013531 (Academic, 2023).","DOI":"10.1016\/B978-0-12-821618-7.00099-7"},{"key":"1136_CR18","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/nrg3246","volume":"13","author":"M Armanios","year":"2012","unstructured":"Armanios, M. & Blackburn, E. H. The telomere syndromes. Nat. Rev. Genet. 13, 693\u2013704 (2012).","journal-title":"Nat. Rev. Genet."},{"key":"1136_CR19","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.3390\/ijms18112267","volume":"18","author":"T Vasko","year":"2017","unstructured":"Vasko, T., Kaifie, A., Stope, M. B., Kraus, T. & Ziegler, P. Telomeres and telomerase in hematopoietic dysfunction: Prognostic implications and pharmacological interventions. Int. J. Mol. Sci. 18, 2267 (2017).","journal-title":"Int. J. Mol. Sci."},{"key":"1136_CR20","doi-asserted-by":"crossref","unstructured":"Carvalho, V. S., Gomes, W. R. & Calado, R. T. Recent advances in understanding telomere diseases. Fac. Rev. 11, 31 (2022).","DOI":"10.12703\/r\/11-31"},{"key":"1136_CR21","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1080\/17474086.2022.2108784","volume":"15","author":"H Tummala","year":"2022","unstructured":"Tummala, H., Walne, A. & Dokal, I. The biology and management of dyskeratosis congenita and related disorders of telomeres. Expert Rev. Hematol. 15, 685\u2013696 (2022).","journal-title":"Expert Rev. Hematol."},{"key":"1136_CR22","doi-asserted-by":"crossref","unstructured":"Kam, M. L. W., Nguyen, T. T. T. & Ngeow, J. Y. Y. Telomere biology disorders. NPJ Genom. Med. 6, 36 (2021).","DOI":"10.1038\/s41525-021-00198-5"},{"key":"1136_CR23","doi-asserted-by":"crossref","unstructured":"Tummala, H. et al. The evolving genetic landscape of telomere biology disorder dyskeratosis congenita. EMBO Mol. Med. 16, 2560\u20132582 (2024).","DOI":"10.1038\/s44321-024-00118-x"},{"key":"1136_CR24","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.hoc.2009.01.003","volume":"23","author":"SA Savage","year":"2009","unstructured":"Savage, S. A. & Alter, B. P. Dyskeratosis congenita. Hematol. Oncol. Clin. North Am. 23, 215\u2013231 (2009).","journal-title":"Hematol. Oncol. Clin. North Am."},{"key":"1136_CR25","doi-asserted-by":"publisher","first-page":"e181659","DOI":"10.1172\/JCI181659","volume":"135","author":"CM Sande","year":"2025","unstructured":"Sande, C. M. et al. ATM-dependent DNA damage response constrains cell growth and drives clonal hematopoiesis in telomere biology disorders. J. Clin. Invest. 135, e181659 (2025).","journal-title":"J. Clin. Invest."},{"key":"1136_CR26","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41576-022-00527-z","volume":"24","author":"P Revy","year":"2023","unstructured":"Revy, P., Kannengiesser, C. & Bertuch, A. A. Genetics of human telomere biology disorders. Nat. Rev. Genet. 24, 86\u2013108 (2023).","journal-title":"Nat. Rev. Genet."},{"key":"1136_CR27","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0092-8674(01)80006-4","volume":"91","author":"MA Blasco","year":"1997","unstructured":"Blasco, M. A. et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25\u201334 (1997).","journal-title":"Cell"},{"key":"1136_CR28","doi-asserted-by":"publisher","first-page":"2767","DOI":"10.1182\/blood.V99.8.2767","volume":"99","author":"E Samper","year":"2002","unstructured":"Samper, E. et al. Long-term repopulating ability of telomerase-deficient murine hematopoietic stem cells. Blood 99, 2767\u20132775 (2002).","journal-title":"Blood"},{"key":"1136_CR29","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1182\/blood-2002-07-2334","volume":"102","author":"RC Allsopp","year":"2003","unstructured":"Allsopp, R. C., Morin, G. B., DePinho, R., Harley, C. B. & Weissman, I. L. Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood 102, 517\u2013520 (2003).","journal-title":"Blood"},{"key":"1136_CR30","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1038\/nm1578","volume":"13","author":"Z Ju","year":"2007","unstructured":"Ju, Z. et al. Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. Nat. Med. 13, 742\u2013747 (2007).","journal-title":"Nat. Med."},{"key":"1136_CR31","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.exger.2015.10.016","volume":"72","author":"J Chen","year":"2015","unstructured":"Chen, J. et al. Hematopoietic lineage skewing and intestinal epithelia degeneration in aged mice with telomerase RNA component deletion. Exp. Gerontol. 72, 251\u2013260 (2015).","journal-title":"Exp. Gerontol."},{"key":"1136_CR32","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/nrm2233","volume":"8","author":"J Campisi","year":"2007","unstructured":"Campisi, J. & D\u2019Adda Di Fagagna, F. Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8, 729\u2013740 (2007).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"1136_CR33","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","volume":"153","author":"C L\u00f3pez-Ot\u00edn","year":"2013","unstructured":"L\u00f3pez-Ot\u00edn, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194 (2013).","journal-title":"Cell"},{"key":"1136_CR34","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1093\/gerona\/glu057","volume":"69","author":"C Franceschi","year":"2014","unstructured":"Franceschi, C. & Campisi, J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. Ser. A 69, S4\u2013S9 (2014).","journal-title":"J. Gerontol. Ser. A"},{"key":"1136_CR35","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/prd.12083","volume":"69","author":"C Zenobia","year":"2015","unstructured":"Zenobia, C. & Hajishengallis, G. Basic biology and role of interleukin-17 in immunity and inflammation. Periodontol. 2000 69, 142\u2013159 (2015).","journal-title":"Periodontol. 2000"},{"key":"1136_CR36","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.ccell.2015.07.006","volume":"28","author":"L Strauss","year":"2015","unstructured":"Strauss, L. et al. RORC1 regulates tumor-promoting \u2018emergency\u2019 granulo-monocytopoiesis. Cancer Cell 28, 253\u2013269 (2015).","journal-title":"Cancer Cell"},{"key":"1136_CR37","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1007\/s00018-022-04200-w","volume":"79","author":"Z Chen","year":"2022","unstructured":"Chen, Z., Guo, Q., Song, G. & Hou, Y. Molecular regulation of hematopoietic stem cell quiescence. Cell. Mol. Life Sci. 79, 218 (2022).","journal-title":"Cell. Mol. Life Sci."},{"key":"1136_CR38","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.cell.2008.10.048","volume":"135","author":"A Wilson","year":"2008","unstructured":"Wilson, A. et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135, 1118\u20131129 (2008).","journal-title":"Cell"},{"key":"1136_CR39","first-page":"54345","volume":"2016","author":"EO Kwarteng","year":"2016","unstructured":"Kwarteng, E. O. & Heinonen, K. M. Competitive transplants to evaluate hematopoietic stem cell fitness. J. Vis. Exp. 2016, 54345 (2016).","journal-title":"J. Vis. Exp."},{"key":"1136_CR40","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s00018-022-04356-5","volume":"79","author":"T Fujino","year":"2022","unstructured":"Fujino, T., Asada, S., Goyama, S. & Kitamura, T. Mechanisms involved in hematopoietic stem cell aging. Cell. Mol. Life Sci. 79, 473 (2022).","journal-title":"Cell. Mol. Life Sci."},{"key":"1136_CR41","doi-asserted-by":"crossref","unstructured":"Hewitt, G. et al. Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat. Commun. 3, 708 (2012).","DOI":"10.1038\/ncomms1708"},{"key":"1136_CR42","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1371\/journal.pone.0110969","volume":"9","author":"M Fumagalli","year":"2014","unstructured":"Fumagalli, M., Rossiello, F., Mondello, C. & d\u2019Adda di Fagagna, F. Stable cellular senescence is associated with persistent DDR activation. PLoS ONE 9, 44\u201346 (2014).","journal-title":"PLoS ONE"},{"key":"1136_CR43","doi-asserted-by":"crossref","unstructured":"Thongon, N. et al. Hematopoiesis under telomere attrition at the single-cell resolution. Nat. Commun. 12, 6850 (2021).","DOI":"10.1038\/s41467-021-27206-7"},{"key":"1136_CR44","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.ccell.2015.04.007","volume":"27","author":"S Colla","year":"2015","unstructured":"Colla, S. et al. Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome. Cancer Cell 27, 644\u2013657 (2015).","journal-title":"Cancer Cell"},{"key":"1136_CR45","doi-asserted-by":"publisher","first-page":"4169","DOI":"10.1182\/blood-2010-08-297390","volume":"117","author":"E Nitta","year":"2011","unstructured":"Nitta, E. et al. Telomerase reverse transcriptase protectsATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism. Blood 117, 4169\u20134180 (2011).","journal-title":"Blood"},{"key":"1136_CR46","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s41581-022-00601-z","volume":"18","author":"W Huang","year":"2022","unstructured":"Huang, W., Hickson, L. T. J., Eirin, A., Kirkland, J. L. & Lerman, L. O. Cellular senescence: the good, the bad and the unknown. Nat. Rev. Nephrol. 18, 611\u2013627 (2022).","journal-title":"Nat. Rev. Nephrol."},{"key":"1136_CR47","doi-asserted-by":"crossref","unstructured":"Jurk, D. et al. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat. Commun. 2, 4172 (2014).","DOI":"10.1038\/ncomms5172"},{"key":"1136_CR48","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/nm0403-369","volume":"9","author":"RC Allsoppi","year":"2003","unstructured":"Allsoppi, R. C. et al. Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells. Nat. Med. 9, 369\u2013371 (2003).","journal-title":"Nat. Med."},{"key":"1136_CR49","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.3324\/haematol.2015.129239","volume":"100","author":"C B\u00e4r","year":"2015","unstructured":"B\u00e4r, C., Huber, N., Beier, F. & Blasco, M. A. Therapeutic effect of androgen therapy in a mouse model of aplastic anemia produced by short telomeres. Haematologica 100, 1267\u20131274 (2015).","journal-title":"Haematologica"},{"key":"1136_CR50","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1182\/blood-2015-08-667485","volume":"127","author":"C B\u00e4r","year":"2016","unstructured":"B\u00e4r, C. et al. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia. Blood 127, 1770\u20131779 (2016).","journal-title":"Blood"},{"key":"1136_CR51","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.stem.2020.03.016","volume":"26","author":"N Nagpal","year":"2020","unstructured":"Nagpal, N. et al. Small-molecule PAPD5 inhibitors restore telomerase activity in patient stem cells. Cell Stem Cell 26, 896\u2013909 (2020).","journal-title":"Cell Stem Cell"},{"key":"1136_CR52","doi-asserted-by":"crossref","unstructured":"Li, X. et al. Mechanisms and rejuvenation strategies for aged hematopoietic stem cells. J Hematol. Oncol. 13, 31 (2020).","DOI":"10.1186\/s13045-020-00864-8"},{"key":"1136_CR53","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.stem.2014.04.014","volume":"14","author":"CW Cheng","year":"2014","unstructured":"Cheng, C. W. et al. Prolonged fasting reduces IGF-1\/PKA to promote hematopoietic-stem-cell- based regeneration and reverse immunosuppression. Cell Stem Cell 14, 810\u2013823 (2014).","journal-title":"Cell Stem Cell"},{"key":"1136_CR54","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.stem.2012.04.007","volume":"10","author":"MC Florian","year":"2012","unstructured":"Florian, M. C. et al. Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell Stem Cell 10, 520\u2013530 (2012).","journal-title":"Cell Stem Cell"},{"key":"1136_CR55","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.jare.2024.04.027","volume":"70","author":"D Gao","year":"2025","unstructured":"Gao, D. et al. Tetrahydroxy stilbene glucoside rejuvenates aging hematopoietic stem cells with predilection for lymphoid differentiation via AMPK and Tet2. J. Adv. Res. 70, 515\u2013529 (2025).","journal-title":"J. Adv. Res."},{"key":"1136_CR56","first-page":"e999","volume":"3","author":"F Rossiello","year":"2013","unstructured":"Rossiello, F., Fumagalli, M. & di Fagagna, F. D. ImmunoFISH for adherent cultured mammalian cells. Bio. Protoc. 3, e999 (2013).","journal-title":"Bio. Protoc."},{"key":"1136_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.142230","volume":"308","author":"A De Chiara","year":"2025","unstructured":"De Chiara, A. et al. Peptide nucleic acid-mediated circularization of target RNA as tool to inhibit translation. Int. J. Biol. Macromol. 308, 142230 (2025).","journal-title":"Int. J. Biol. Macromol."},{"key":"1136_CR58","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20251805","volume":"223","author":"E Lettera","year":"2026","unstructured":"Lettera, E. et al. Molecular and phenotypic blueprint of human hematopoiesis links proliferation stress to stem cell aging. J. Exp. Med. 223, e20251805 (2026).","journal-title":"J. Exp. Med."},{"key":"1136_CR59","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/978-1-4939-8931-7_5","volume":"1896","author":"A Vasilishina","year":"2019","unstructured":"Vasilishina, A., Kropotov, A., Spivak, I. & Bernadotte, A. Relative human telomere length quantification by real-time PCR. Methods Mol. Biol. 1896, 39\u201344 (2019).","journal-title":"Methods Mol. Biol."}],"container-title":["Nature Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s43587-026-01136-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43587-026-01136-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43587-026-01136-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:02:46Z","timestamp":1784206966000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s43587-026-01136-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":59,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["1136"],"URL":"https:\/\/doi.org\/10.1038\/s43587-026-01136-9","relation":{},"ISSN":["2662-8465"],"issn-type":[{"value":"2662-8465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"assertion":[{"value":"10 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"F.dA.dF. and F.R. are inventors on the following patent applications: RNA products and uses thereof (PCT\/EP2013\/059753); Therapeutic oligonucleotides (PCT\/EP2016\/068162). F.dA.dF. is a shareholder of TAG Therapeutics. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}