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@ARTICLE{Minetti:306547,
      author       = {A. Minetti and O. Omrani and C. Brenner and F. Cansiz$^*$
                      and S. Imada and J. Rösler$^*$ and S. Khawaled and G.
                      Allies and S. W. Meckelmann and N. Gebert and I. Heinze and
                      N. Rahnis and J. Lu and K. Spengler and M. Rasa and E. Cirri
                      and R. Heller and Ö. Yilmaz and A. Tasdogan$^*$ and F. Neri
                      and A. Ori},
      title        = {{P}olyamines sustain epithelial regeneration in aged
                      intestines by modulating protein homeostasis.},
      journal      = {Nature cell biology},
      volume       = {nn},
      issn         = {1465-7392},
      address      = {New York, NY},
      publisher    = {Nature America},
      reportid     = {DKFZ-2025-02612},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {Ageing dampens the regenerative potential of intestinal
                      epithelium across species including humans, yet the
                      underlying causes remain elusive. Here we characterized the
                      temporal dynamics of regeneration following injury induced
                      by 5-fluorouracil, a commonly used chemotherapeutic agent,
                      using proteomic and metabolomic profiling of intestinal
                      tissues together with functional assays. The comparison of
                      regeneration dynamics in mice of different ages revealed the
                      emergence of proteostasis stress and increased levels of
                      polyamines following injury exclusively in old epithelia. We
                      show that delayed regeneration is an intrinsic feature of
                      aged epithelial cells that display reduced protein synthesis
                      and the accumulation of ubiquitylated proteins. The
                      inhibition of the polyamine pathway in vivo further delays
                      regeneration in old mice, whereas its activation by dietary
                      intervention or supplementation of polyamines is sufficient
                      to enhance the regenerative capacity of aged intestines. Our
                      findings highlight the promising epithelial targets for
                      interventions aimed at tackling the decline in tissue repair
                      mechanisms associated with ageing.},
      cin          = {ED01},
      ddc          = {570},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41286441},
      doi          = {10.1038/s41556-025-01804-9},
      url          = {https://inrepo02.dkfz.de/record/306547},
}