Yak collagen peptides inhibit MMP-1 and extend worm lifespan

Computational screening followed by experimental testing identified three peptides derived from yak bone collagen that inhibited MMP-1 and extended the lifespan of the nematode Caenorhabditis elegans under the tested conditions. Reported as an early-access, peer-reviewed article in npj Science of Food, the study presents a combined computational and laboratory strategy for identifying collagen-derived peptides as potential functional-food ingredients.

The researchers developed AgeAttnMLP, a screening model based on the ESM-2 protein language model, to prioritize candidate bioactive peptides from yak collagen sequences. The model achieved an AUC of 0.891 under conventional five-fold cross-validation and 0.879 in an additional cluster-aware grouped evaluation. After screening yak collagen sequences, the team used Alcalase-guided in silico hydrolysis to select TGPPGPSGI, GEPGAPGE and GPSGEPGTA for experimental testing.

GEPGAPGE showed the strongest measured MMP-1 inhibition among the three candidates, with an IC50 of 126 μg/mL. Molecular-dynamics simulations and MM-PBSA binding-energy analyses suggested that peptide binding destabilized a β-sheet spanning residues 76–78 near MMP-1’s catalytic region, potentially affecting substrate recognition. That structural interpretation came from computational analysis; the supplied findings do not report direct experimental confirmation of the proposed mechanism. All three peptides also extended C. elegans lifespan, with the greatest effect observed for GPSGEPGTA at 7.5 mg/mL.

The results connect two measured outcomes—MMP-1 inhibition in laboratory assays and increased lifespan in worms—but do not establish that MMP-1 inhibition caused the longevity effect. The experiments involved an enzyme assay, computational analyses and an animal model rather than human participants, so they do not demonstrate clinical anti-aging benefits, safety or efficacy in people. By integrating sequence-based prediction, targeted peptide generation and experimental validation, the study shows how yak bone collagen byproducts can serve as a source of peptides with measurable MMP-1 inhibitory activity and lifespan effects in C. elegans. Its conclusions remain limited to the tested compounds, concentrations and experimental systems.

Subject of Research: Computational and experimental screening of anti-aging peptides derived from yak bone collagen byproducts

Article Title: Valorization of yak bone collagen byproducts: computational screening and experimental validation of anti-aging peptides targeting MMP-1

Article References: Liu, Y., Zhang, Y., Li, Q., Zhuang, J., Li, W., & Han, W. (2026). Valorization of yak bone collagen byproducts: computational screening and experimental validation of anti-aging peptides targeting MMP-1. npj Science of Food. https://doi.org/10.1038/s41538-026-01223-6

Image Credits: AI Generated

DOI: 10.1038/s41538-026-01223-6

Keywords: yak collagen, bioactive peptides, MMP-1 inhibition, Caenorhabditis elegans, protein language model, molecular dynamics, food byproducts, functional foods, lifespan extension, Valorization, bone, collagen