MassIVE MSV000094212

Partial Public PXD050266

Polyamines sustain epithelial regeneration of aged intestine

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Description

Aging reduces the regenerative capacity of the intestinal epithelium in different species including humans. The causes of delayed regeneration in the elderly remain unclear. Here, we used proteomic and metabolomic profiling of intestinal tissues together with functional assays to characterize the dynamics of regeneration following injury induced by 5-fluorouracil, a commonly used chemotherapeutic agent. Comparison of regeneration dynamics in mice of different ages revealed emergence of a proteostasis stress signature and increased levels of polyamines following injury exclusively in old epithelia. Mechanistically, we show that delayed regeneration is a cell-intrinsic feature of old epithelial cells that display reduced protein synthesis and accumulation of ubiquitylated proteins. We demonstrate that an intervention based on dietary restriction followed by re-feeding prior to injury elevates intracellular polyamine levels, alleviates proteostasis stress and restores the regenerative capacity of the old intestines. Our work provides novel targets and strategies to improve intestinal regeneration in the elderly. [doi:10.25345/C50Z71749] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Intestinal regeneration Protein homeostasis Polyamine metabolism

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Principal Investigators:
(in alphabetical order) 		Alessandro Ori, Leibniz Institute on Aging Fritz Lipmann Institute (FLI), Germany
Submitting User: ProteomicsCF_FLI
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