Polyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis.

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 furth

SUBMITTER: Minetti A 

PROVIDER: S-EPMC12717014 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature