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To investigate the basis of organ\u2010specific ageing, we utilized progeroid repair\u2010deficient\n                    <jats:italic>\n                      Ercc1\n                      <jats:sup>\u0394<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:sup>\/\u2212<\/jats:sup>\n                    mouse mutants and systematically compared at the tissue, stem cell and organoid level two organs representing ageing extremes.\n                    <jats:italic>\n                      Ercc1\n                      <jats:sup>\u0394<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:sup>\/\u2212<\/jats:sup>\n                    intestine shows hardly any accelerated ageing. Nevertheless, we found apoptosis and reduced numbers of intestinal stem cells (ISCs), but cell loss appears compensated by over\u2010proliferation. ISCs retain their organoid\u2010forming capacity, but organoids perform poorly in culture, compared with WT. Conversely, liver ages dramatically, even causing early death in\n                    <jats:italic>Ercc1<\/jats:italic>\n                    \u2010KO mice. Apoptosis, p21, polyploidization and proliferation of various (stem) cells were prominently elevated in\n                    <jats:italic>\n                      Ercc1\n                      <jats:sup>\u0394<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:sup>\/\u2212<\/jats:sup>\n                    liver and stem cell populations were either largely unaffected (Sox9+), or expanding (Lgr5+), but were functionally exhausted in organoid formation and development\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Paradoxically, while intestine displays less ageing, repair in WT ISCs appears inferior to liver as shown by enhanced sensitivity to various DNA\u2010damaging agents, and lower lesion removal. Our findings reveal organ\u2010specific anti\u2010ageing strategies. Intestine, with short lifespan limiting time for damage accumulation and repair, favours apoptosis of damaged cells relying on ISC plasticity. Liver with low renewal rates depends more on repair pathways specifically protecting the transcribed compartment of the genome to promote sustained functionality and cell preservation. As shown before, the hematopoietic system with intermediate self\u2010renewal mainly invokes replication\u2010linked mechanisms, apoptosis and senescence. Hence, organs employ different genome maintenance strategies, explaining heterogeneity in organ ageing and the segmental nature of DNA\u2010repair\u2010deficient progerias.\n                  <\/jats:p>","DOI":"10.1111\/acel.13562","type":"journal-article","created":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T02:42:45Z","timestamp":1646448165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Different responses to DNA damage determine ageing differences between organs"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9868-820X","authenticated-orcid":false,"given":"Maria","family":"Vougioukalaki","sequence":"first","affiliation":[{"name":"Department Molecular Genetics Erasmus University Medical Center Rotterdam  Rotterdam The 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