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000306547 1001_ $$aMinetti, Alberto$$b0
000306547 245__ $$aPolyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis.
000306547 260__ $$aNew York, NY$$bNature America$$c2025
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000306547 520__ $$aAgeing dampens the regenerative potential of intestinal epithelium across species including humans, yet the underlying causes remain elusive. Here we characterized the temporal dynamics of regeneration following injury induced by 5-fluorouracil, a commonly used chemotherapeutic agent, using proteomic and metabolomic profiling of intestinal tissues together with functional assays. The comparison of regeneration dynamics in mice of different ages revealed the emergence of proteostasis stress and increased levels of polyamines following injury exclusively in old epithelia. We show that delayed regeneration is an intrinsic feature of aged epithelial cells that display reduced protein synthesis and the accumulation of ubiquitylated proteins. The inhibition of the polyamine pathway in vivo further delays regeneration in old mice, whereas its activation by dietary intervention or supplementation of polyamines is sufficient to enhance the regenerative capacity of aged intestines. Our findings highlight the promising epithelial targets for interventions aimed at tackling the decline in tissue repair mechanisms associated with ageing.
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000306547 7001_ $$00000-0002-9902-3477$$aOmrani, Omid$$b1
000306547 7001_ $$aBrenner, Christiane$$b2
000306547 7001_ $$0P:(DE-He78)ad58ab6767c6050391bd98a99f46e1e5$$aCansiz, Feyza$$b3$$udkfz
000306547 7001_ $$aImada, Shinya$$b4
000306547 7001_ $$0P:(DE-HGF)0$$aRösler, Jonas$$b5
000306547 7001_ $$aKhawaled, Saleh$$b6
000306547 7001_ $$aAllies, Gabriele$$b7
000306547 7001_ $$aMeckelmann, Sven W$$b8
000306547 7001_ $$aGebert, Nadja$$b9
000306547 7001_ $$aHeinze, Ivonne$$b10
000306547 7001_ $$00000-0001-8424-9919$$aRahnis, Norman$$b11
000306547 7001_ $$aLu, Jing$$b12
000306547 7001_ $$00000-0001-9611-7841$$aSpengler, Katrin$$b13
000306547 7001_ $$aRasa, Mahdi$$b14
000306547 7001_ $$aCirri, Emilio$$b15
000306547 7001_ $$aHeller, Regine$$b16
000306547 7001_ $$00000-0002-7577-4612$$aYilmaz, Ömer$$b17
000306547 7001_ $$00000-0003-2543-852X$$aTasdogan, Alpaslan$$b18
000306547 7001_ $$00000-0003-3903-1974$$aNeri, Francesco$$b19
000306547 7001_ $$00000-0002-3046-0871$$aOri, Alessandro$$b20
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