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

<h4>Background</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.