ACE‐inhibitory peptide Leu‐Tyr‐Ala in skeletal muscle actin exhibits anti‐aging effects through the inhibition of acn‐1 in Caenorhabditis elegans

BACKGROUND: Inhibitors of angiotensin‐converting enzyme (ACE) are used in pharmaceuticals and functional foods. Captopril, a well‐known ACE inhibitor, extends the lifespan of the nematode Caenorhabditis elegans. Bioactive peptides derived from food sources are considered safe ACE inhibitors. Previously, we identified the sequence Asp‐Leu‐Tyr‐Ala in skeletal muscle actin and its derivatives, Leu‐Tyr‐Ala, Leu‐Tyr, and Tyr‐Ala, as antioxidant peptides. In the present study, we evaluated the ACE‐inhibitory activity of peptides and their anti‐aging effects in a C. elegans model. RESULTS: Among the four peptides, Leu‐Tyr‐Ala showed the highest ACE‐inhibitory activity in vitro. Leu‐Tyr‐Ala delayed the increase in body length and width in C. elegans but did not affect reproductive ability. The average lifespan of C. elegans treated with 5 mmol/L Leu‐Tyr‐Ala was 26% longer than that of the control group. The treatment of Leu‐Tyr‐Ala also improved locomotor activity, enhanced resistance to oxidative and thermal stress, reduced fat accumulation, and decreased lipofuscin levels in C. elegans. In addition, Leu‐Tyr‐Ala down‐regulated the messenger RNA (mRNA) expression of acn‐1 (a homolog of mammalian ACE in C. elegans) and up‐regulated the mRNA expression of antioxidant (ctl‐1, gst‐4, mtl‐1, and hsp‐70), muscle‐related (unc‐54 and myo‐3), and fat metabolism (daf‐36, fat‐5, and fat‐7) via daf‐12 and daf‐16. Furthermore, a life‐prolonging effect was not observed in daf‐12 and daf‐16 mutants, suggesting that Leu‐Tyr‐Ala may inhibit acn‐1 function and exert anti‐aging effects through daf‐12 and daf‐16. CONCLUSION: Our findings provide evidence that ACE‐inhibitory peptides can be used as functional food ingredients with anti‐aging properties. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.