An in vivo resource of age-regulated C. elegans intestinal secretory-pathway proteins highlights secreted enzymes associated with lifespan regulation
14 affiliations
- 1Department of Genetics, Stanford University, Stanford, CA, USA
- 2Present address: Institute of Molecular Biology (IMB), Mainz, Germany
- 3Biomedical Informatics Graduate Program, Stanford University, Stanford, CA, USA
- 4Stanford Biophysics Graduate Program, Stanford University, Stanford, CA, USA
- 5Arc Institute, Palo Alto, CA 94304, USA
- 6Department of Chemical Engineering, Stanford University, Stanford, CA, USA
- 7The Institute for Chemistry, Engineering & Medicine for Human Health, Stanford University, Stanford, CA, USA
- 8Present address: Arc Institute, Palo Alto, CA 94304, USA
- 9Biohub, San Francisco, CA, USA
- 10Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- 11Stanford Medical Scientist Training Program, Stanford University, Stanford, CA, USA
- 12Glenn Center for the Biology of Aging, Stanford University, Stanford, CA, USA
- 13Wu Tsai Institute of Neurosciences, Stanford University, Stanford, CA, USA
- 14Lead contact
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.
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BibTeX
@article{miklas2026vivo,
title = {{An in vivo resource of age-regulated C. elegans intestinal secretory-pathway proteins highlights secreted enzymes associated with lifespan regulation}},
author = {Jason W. Miklas and Katharina Papsdorf and Eric D. Sun and Aleksandra Tsenter and Nicole R. Haseley and Brandon Ameglio and Uche N. Medoh and Daniel Richard and Frank McCarthy and Karen L. Artiles and Andy Hims and Aleksandra Levina and Olivia Y. Zhou and Joshua E. Elias and Monther Abu-Remaileh and Anne Brunet},
journal = {Cell reports},
year = {2026},
month = aug,
doi = {10.1016/j.celrep.2026.117902},
url = {https://doi.org/10.1016/j.celrep.2026.117902},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - An in vivo resource of age-regulated C. elegans intestinal secretory-pathway proteins highlights secreted enzymes associated with lifespan regulation
AU - Jason W. Miklas
AU - Katharina Papsdorf
AU - Eric D. Sun
AU - Aleksandra Tsenter
AU - Nicole R. Haseley
AU - Brandon Ameglio
AU - Uche N. Medoh
AU - Daniel Richard
AU - Frank McCarthy
AU - Karen L. Artiles
AU - Andy Hims
AU - Aleksandra Levina
AU - Olivia Y. Zhou
AU - Joshua E. Elias
AU - Monther Abu-Remaileh
AU - Anne Brunet
PY - 2026
DA - 2026/08/27
JO - Cell reports
DO - 10.1016/j.celrep.2026.117902
UR - https://doi.org/10.1016/j.celrep.2026.117902
AB - 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.
SN - 2211-1247
ER -