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.