TY  - JOUR
AU  - Minetti, Alberto
AU  - Omrani, Omid
AU  - Brenner, Christiane
AU  - Cansiz, Feyza
AU  - Imada, Shinya
AU  - Rösler, Jonas
AU  - Khawaled, Saleh
AU  - Allies, Gabriele
AU  - Meckelmann, Sven W
AU  - Gebert, Nadja
AU  - Heinze, Ivonne
AU  - Rahnis, Norman
AU  - Lu, Jing
AU  - Spengler, Katrin
AU  - Rasa, Mahdi
AU  - Cirri, Emilio
AU  - Heller, Regine
AU  - Yilmaz, Ömer
AU  - Tasdogan, Alpaslan
AU  - Neri, Francesco
AU  - Ori, Alessandro
TI  - Polyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis.
JO  - Nature cell biology
VL  - nn
SN  - 1465-7392
CY  - New York, NY
PB  - Nature America
M1  - DKFZ-2025-02612
SP  - nn
PY  - 2025
N1  - epub
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:41286441
DO  - DOI:10.1038/s41556-025-01804-9
UR  - https://inrepo02.dkfz.de/record/306547
ER  -