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

Authors

Jason W Miklas, Katharina Papsdorf, Eric D Sun, Aleksandra Tsenter, Nicole R Haseley, Brandon Ameglio, Uche N Medoh, Daniel Richard, Frank McCarthy, Karen L Artiles, Andy Hims, Aleksandra Levina, Olivia Y Zhou, Joshua E Elias, Monther Abu-Remaileh, Anne Brunet

Published in

Cell reports. Volume 45. Issue 9. Pages 117902. Aug 27, 2026. Epub Aug 27, 2026.

Abstract

Secreted proteins are essential to modulate homeostasis in the extracellular space and facilitate communication to distal cells or tissues. Yet, the identity and functional importance of extracellular proteins in aging have been understudied. Here we use proximity labeling followed by quantitative proteomics to systematically characterize proteins along the intestinal secretory pathway in C. elegans, focusing on secreted proteins. We identify intestine-secreted proteins that are modulated with age, and validate the secretion of these proteins in vivo. One of these secreted proteins, ACP7, is well conserved in humans, and its overexpression extends lifespan in a secretion-dependent manner. Interestingly, we find that ACP7 acts as a secreted phosphatase in the extracellular space. Finally, we identify additional proteins along the secretory pathway that regulate lifespan. Our systematic characterization of tissue-specific secreted proteins during aging uncovers conserved proteins that impact lifespan and highlights extracellular enzymes associated with lifespan regulation.

PMID:
42658673
Bibliographic data and abstract were imported from PubMed on 28 Aug 2026.

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