Dataset Information

An in vivo resource of age-regulated C. elegans intestinal secretory-pathway proteins highlights secreted enzymes associated with lifespan regulation

ABSTRACT: Secreted proteins are essential to modulate the extracellular space and communicate long-distances to distal cells or tissues. But the importance of extracellular proteins in aging has been vastly understudied. Identifying how the ‘secretome’ – the ensemble of secreted proteins and secretion machinery – changes with age and impacts lifespan would provide a new understanding of aging, focused on the extracellular milieu. Here we characterize the secretome of Caenorhabditis elegans’ intestine – a well conserved tissue that is important for healthy longevity. To capture the intestine secretome, we use proximity labeling with TurboID-ER, an engineered protein that labels proteins in the endoplasmic reticulum where all secreted proteins transit. Using this proximity labeling tool followed by quantitative proteomics, we systematically characterize the intestine secretome during aging, which reveals many previously unknown secreted proteins that change with age. We validate the secreted nature of these proteins by leveraging the ability to perform cell biology in vivo in C. elegans. One of these secreted proteins, ACP7/F21A3.11, is well conserved in humans. We find that overexpressing wildtype ACP7, but not a non-secreted mutant, extends lifespan, underscoring the importance of this protein in the extracellular space for lifespan regulation. We also show that ACP7 acts as a phosphatase and that its enzymatic activity in the extracellular space is important for organismal health. Finally, by performing a targeted screen, we identify additional secretome proteins that regulate lifespan when knocked-down, including VAPA/F53B6.4 – a protein localized to small vesicles of the secretion machinery. Our work systematically characterizes the aging intestine secretome, which uncovers previously uncharacterized proteins that play a functional role in lifespan. Our study also highlights how enzymatic activity in the extracellular space could be critical for health.

INSTRUMENT(S):

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: Frank McCarthy

LAB HEAD: Anne Brunet

PROVIDER: PXD057064 | Pride | 2026-07-28

REPOSITORIES: Pride

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			Action	DRS
	16to30_TMTSet1_F1_R1_T1_MCMS3Top10SPS10300nl_000924_ANBR001_FL2.raw	Raw
	16to30_TMTSet1_F2_R1_T1_MCMS3Top10SPS10300nl_000925_ANBR001_FL2.raw	Raw
	16to30_TMTSet1_F3_R1_T1_MCMS3Top10SPS10300nl_000926_ANBR001_FL2.raw	Raw
	16to30_TMTSet1_F4_R1_T1_MCMS3Top10SPS10300nl_000927_ANBR001_FL2.raw	Raw
	16to30_TMTSet1_F5_R1_T1_MCMS3Top10SPS10300nl_000928_ANBR001_FL2.raw	Raw

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Project description:Gebauer2016 - Genome-scale model of Caenorhabditis elegans metabolism (without bacteria) This model is one of the two versions of ElegCyc presented in the paper. It describes the metabolism of a worm raised in a medium without bacteria. This model is described in the article: A Genome-Scale Database and Reconstruction of Caenorhabditis elegans Metabolism. Gebauer J, Gentsch C, Mansfeld J, Schmeißer K, Waschina S, Brandes S, Klimmasch L, Zamboni N, Zarse K, Schuster S, Ristow M, Schäuble S, Kaleta C. Cell Syst 2016 May; 2(5): 312-322 Abstract: We present a genome-scale model of Caenorhabditis elegans metabolism along with the public database ElegCyc (http://elegcyc.bioinf.uni-jena.de:1100), which represents a reference for metabolic pathways in the worm and allows for the visualization as well as analysis of omics datasets. Our model reflects the metabolic peculiarities of C. elegans that make it distinct from other higher eukaryotes and mammals, including mice and humans. We experimentally verify one of these peculiarities by showing that the lifespan-extending effect of L-tryptophan supplementation is dose dependent (hormetic). Finally, we show the utility of our model for analyzing omics datasets through predicting changes in amino acid concentrations after genetic perturbations and analyzing metabolic changes during normal aging as well as during two distinct, reactive oxygen species (ROS)-related lifespan-extending treatments. Our analyses reveal a notable similarity in metabolic adaptation between distinct lifespan-extending interventions and point to key pathways affecting lifespan in nematodes. This model is hosted on BioModels Database and identified by: MODEL1704200000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Gebauer2016 - Genome-scale model of Caenorhabditis elegans metabolism (with bacteria) This model is one of the two versions of ElegCyc presented in the paper. It describes the metabolism of a worm raised in a medium with bacteria This model is described in the article: A Genome-Scale Database and Reconstruction of Caenorhabditis elegans Metabolism. Gebauer J, Gentsch C, Mansfeld J, Schmeißer K, Waschina S, Brandes S, Klimmasch L, Zamboni N, Zarse K, Schuster S, Ristow M, Schäuble S, Kaleta C. Cell Syst 2016 May; 2(5): 312-322 Abstract: We present a genome-scale model of Caenorhabditis elegans metabolism along with the public database ElegCyc (http://elegcyc.bioinf.uni-jena.de:1100), which represents a reference for metabolic pathways in the worm and allows for the visualization as well as analysis of omics datasets. Our model reflects the metabolic peculiarities of C. elegans that make it distinct from other higher eukaryotes and mammals, including mice and humans. We experimentally verify one of these peculiarities by showing that the lifespan-extending effect of L-tryptophan supplementation is dose dependent (hormetic). Finally, we show the utility of our model for analyzing omics datasets through predicting changes in amino acid concentrations after genetic perturbations and analyzing metabolic changes during normal aging as well as during two distinct, reactive oxygen species (ROS)-related lifespan-extending treatments. Our analyses reveal a notable similarity in metabolic adaptation between distinct lifespan-extending interventions and point to key pathways affecting lifespan in nematodes. This model is hosted on BioModels Database and identified by: MODEL1704200001. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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An in vivo resource of age-regulated C. elegans intestinal secretory-pathway proteins highlights secreted enzymes associated with lifespan regulation

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