PXD057064

PXD057064 is an original dataset announced via ProteomeXchange.

Title	An in vivo resource of age-regulated C. elegans intestinal secretory-pathway proteins highlights secreted enzymes associated with lifespan regulation
Description	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.
HostingRepository	PRIDE
AnnounceDate	2026-07-28
AnnouncementXML	Submission_2026-07-27_22:39:56.922.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank McCarthy
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: NEWT:6239;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-22 11:05:01	ID requested
⏵ 1	2026-07-27 22:39:57	announced

Dataset with its publication pending

submitter keyword: Caenorhabditis elegans, longevity, secretome, aging

Anne Brunet
contact affiliation	Professor of Genetics, School of Medicine, Stanford, USA
contact email	abrunet1@stanford.edu
lab head
Frank McCarthy
contact affiliation	CZ Biohub
contact email	frank.mccarthy@czbiohub.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/07/PXD057064

PRIDE project URI

• PRIDE
  1. PXD057064
     1. Label: PRIDE project
     2. Name: An in vivo resource of age-regulated C. elegans intestinal secretory-pathway proteins highlights secreted enzymes associated with lifespan regulation