ArticleNature communications2019
Loss of a proteostatic checkpoint in intestinal stem cells contributes to age-related epithelial dysfunction.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Non-gonadal PIWIL1/Aubergine drives regenerative and tumorigenic stem cell proliferation and tumorigenesis in the intestine.Cell reports · 2026Article
- Toll signaling controls stem cell proliferation in intestinal regeneration and tumorigenesis.EMBO reports · 2026Article
- Peripheral modulation of Pumilio in intestinal stem cells and the corpus allatum affects sleep latency in Drosophila.PloS one · 2026Article
- Dysbiosis and the gut-brain axis impairment in the pathophysiology of Alzheimer's disease and related dementias: is 'pathobiome' an etiological element?Essays in biochemistry · 2025Review
- Polyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis.Nature cell biology · 2025Article
- MG132-mediated Suppression of the Ubiquitin-proteasome Pathway Enhances the Sensitivity of Endometrial Cancer Cells to Cisplatin.Anti-cancer agents in medicinal chemistry · 2025Article
- Induction of proteasomal activity in mammalian cells by lifespan-extending tRNA synthetase inhibitors.GeroScience · 2024Article
- Interplay between autophagy and CncC regulates dendrite pruning inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Heat-inactivated Bifidobacterium adolescentis ameliorates colon senescence through Paneth-like-cell-mediated stem cell activation.Nature communications · 2023Article
- Curcumin in vitro Neuroprotective Effects Are Mediated by p62/keap-1/Nrf2 and PI3K/AKT Signaling Pathway and Autophagy Inhibition.Physiological research · 2023Article
- CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro.Journal of translational medicine · 2023Article
- Article
- The CRTC-CREB axis functions as a transcriptional sensor to protect against proteotoxic stress in Drosophila.Cell death & disease · 2022Article
- Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease.Journal of advanced research · 2022Review
- Studies on the Regulation and Molecular Mechanism of Panax Ginseng Saponins on Senescence and Related Behaviors ofFrontiers in aging neuroscience · 2022Article
- How autophagy controls the intestinal epithelial barrier.Autophagy · 2022Review
- Aspirin Positively Contributes toAging and disease · 2021Article
- Metabolic Regulation of Stem Cells in Aging.Current stem cell reports · 2021Article
- Age-related changes in polycomb gene regulation disrupt lineage fidelity in intestinal stem cells.eLife · 2021Article
- An NRF2 Perspective on Stem Cells and Ageing.Frontiers in aging · 2021Review
Corrections and comments
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3 authors.
Funding
Abstract
A decline in protein homeostasis (proteostasis) has been proposed as a hallmark of aging. Somatic stem cells (SCs) uniquely maintain their proteostatic capacity through mechanisms that remain incompletely understood. Here, we describe and characterize a 'proteostatic checkpoint' in Drosophila intestinal SCs (ISCs). Following a breakdown of proteostasis, ISCs coordinate cell cycle arrest with protein aggregate clearance by Atg8-mediated activation of the Nrf2-like transcription factor cap-n-collar C (CncC). CncC induces the cell cycle inhibitor Dacapo and proteolytic genes. The capacity to engage this checkpoint is lost in ISCs from aging flies, and we show that it can be restored by treating flies with an Nrf2 activator, or by over-expression of CncC or Atg8a. This limits age-related intestinal barrier dysfunction and can result in lifespan extension. Our findings identify a new mechanism by which somatic SCs preserve proteostasis, and highlight potential intervention strategies to maintain regenerative homeostasis.
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