{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:11:22Z","timestamp":1786115482260,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21H02348"],"award-info":[{"award-number":["JP21H02348"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22J00122"],"award-info":[{"award-number":["JP22J00122"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP26K18015"],"award-info":[{"award-number":["JP26K18015"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Sci Food Agric"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Inhibitors of angiotensin\u2010converting enzyme (ACE) are used in pharmaceuticals and functional foods. Captopril, a well\u2010known ACE inhibitor, extends the lifespan of the nematode\n                      <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                      . Bioactive peptides derived from food sources are considered safe ACE inhibitors. Previously, we identified the sequence Asp\u2010Leu\u2010Tyr\u2010Ala in skeletal muscle actin and its derivatives, Leu\u2010Tyr\u2010Ala, Leu\u2010Tyr, and Tyr\u2010Ala, as antioxidant peptides. In the present study, we evaluated the ACE\u2010inhibitory activity of peptides and their anti\u2010aging effects in a\n                      <jats:italic>C. elegans<\/jats:italic>\n                      model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among the four peptides, Leu\u2010Tyr\u2010Ala showed the highest ACE\u2010inhibitory activity\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Leu\u2010Tyr\u2010Ala delayed the increase in body length and width in\n                      <jats:italic>C. elegans<\/jats:italic>\n                      but did not affect reproductive ability. The average lifespan of\n                      <jats:italic>C. elegans<\/jats:italic>\n                      treated with 5\u2009mmol\/L Leu\u2010Tyr\u2010Ala was 26% longer than that of the control group. The treatment of Leu\u2010Tyr\u2010Ala also improved locomotor activity, enhanced resistance to oxidative and thermal stress, reduced fat accumulation, and decreased lipofuscin levels in\n                      <jats:italic>C. elegans<\/jats:italic>\n                      . In addition, Leu\u2010Tyr\u2010Ala down\u2010regulated the messenger RNA (mRNA) expression of\n                      <jats:italic>acn\u20101<\/jats:italic>\n                      (a homolog of mammalian ACE in\n                      <jats:italic>C. elegans<\/jats:italic>\n                      ) and up\u2010regulated the mRNA expression of antioxidant (\n                      <jats:italic>ctl\u20101<\/jats:italic>\n                      ,\n                      <jats:italic>gst\u20104<\/jats:italic>\n                      ,\n                      <jats:italic>mtl\u20101<\/jats:italic>\n                      , and\n                      <jats:italic>hsp\u201070<\/jats:italic>\n                      ), muscle\u2010related (\n                      <jats:italic>unc\u201054<\/jats:italic>\n                      and\n                      <jats:italic>myo\u20103<\/jats:italic>\n                      ), and fat metabolism (\n                      <jats:italic>daf\u201036<\/jats:italic>\n                      ,\n                      <jats:italic>fat\u20105<\/jats:italic>\n                      , and\n                      <jats:italic>fat\u20107<\/jats:italic>\n                      ) via\n                      <jats:italic>daf\u201012<\/jats:italic>\n                      and\n                      <jats:italic>daf\u201016<\/jats:italic>\n                      . Furthermore, a life\u2010prolonging effect was not observed in\n                      <jats:italic>daf\u201012<\/jats:italic>\n                      and\n                      <jats:italic>daf\u201016<\/jats:italic>\n                      mutants, suggesting that Leu\u2010Tyr\u2010Ala may inhibit\n                      <jats:italic>acn\u20101<\/jats:italic>\n                      function and exert anti\u2010aging effects through\n                      <jats:italic>daf\u201012<\/jats:italic>\n                      and\n                      <jats:italic>daf\u201016<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Our findings provide evidence that ACE\u2010inhibitory peptides can be used as functional food ingredients with anti\u2010aging properties. \u00a9 2026 The Author(s).\n                      <jats:italic>Journal of the Science of Food and Agriculture<\/jats:italic>\n                      published by John Wiley &amp; Sons Ltd on behalf of Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsfa.70730","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:23:01Z","timestamp":1778818981000},"page":"7002-7014","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ACE<\/scp>\n                    \u2010inhibitory peptide\n                    <scp>Leu\u2010Tyr\u2010Ala<\/scp>\n                    in skeletal muscle actin exhibits anti\u2010aging effects through the inhibition of\n                    <i>acn\u20101<\/i>\n                    in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1002","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1998-0200","authenticated-orcid":false,"given":"Issei","family":"Yokoyama","sequence":"first","affiliation":[{"name":"Department of Animal Science, School of Veterinary Medicine Kitasato University  Towada Japan"},{"name":"Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minori","family":"Yamane","sequence":"additional","affiliation":[{"name":"Department of Animal Science, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanaho","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Animal Science, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3954-0868","authenticated-orcid":false,"given":"Abdul","family":"Fatah","sequence":"additional","affiliation":[{"name":"Department of Animal Science, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3225-2491","authenticated-orcid":false,"given":"Yusuke","family":"Komiya","sequence":"additional","affiliation":[{"name":"Department of Animal Science, School of Veterinary Medicine Kitasato University  Towada Japan"},{"name":"Department of Food Sciences and Technology College of Bioresource Sciences, Nihon University  Fujisawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6711-8976","authenticated-orcid":false,"given":"Jun","family":"Nagasao","sequence":"additional","affiliation":[{"name":"Department of Animal Science, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9035-3189","authenticated-orcid":false,"given":"Keizo","family":"Arihara","sequence":"additional","affiliation":[{"name":"Department of Animal Science, School of Veterinary Medicine Kitasato University  Towada Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.04.011"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(92)90281-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf052263o"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14214637"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.17306\/J.AFS.2015.3.19"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43014-019-0002-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meatsci.2021.108561"},{"key":"e_1_2_9_9_1","article-title":"Bioactive peptide\u2010enriched deer meat sauce: a novel functional food innovation","volume":"5","author":"Kogiso K","year":"2025","journal-title":"Food Mater Res"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.5713\/ab.23.0433"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bbb\/zbae171"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crfs.2022.05.001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020085"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/07924259.2014.940470"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.554994"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2021.104750"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/jfbc\/1975661"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308858200"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005866"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.202146"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glz152"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.06.018"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meatsci.2006.04.028"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/jfbc\/1717607"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/77.1.71"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2020.100276"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2023.102285"},{"key":"e_1_2_9_28_1","volume-title":"The Anti\u2010Obesity Effects of the Angiotensin\u2010Converting Enzyme (ACE) Inhibitor Captopril \u2013 Metabolomics and Transcriptomics Studies","author":"Kucuktepe S","year":"2021"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2016.12.002"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9040316"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms140611895"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8FO02371A"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.132833"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meatsci.2025.109980"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2013.01.010"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.8.2305"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-9-r188"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2011.00733.x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021173"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","unstructured":"NichiteanAM CompereFVandHallSE Oleic acid decouples fecundity and longevity via DAF\u201012 steroid hormone signaling inC. elegans bioRxiv(2023).https:\/\/doi.org\/10.1101\/2023.04.13.536759.","DOI":"10.1101\/2023.04.13.536759"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030053"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13765-022-00685-y"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.092064799"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.690373"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsfa.13348"}],"container-title":["Journal of the Science of Food and Agriculture"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsfa.70730","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jsfa.70730","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsfa.70730","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T03:11:05Z","timestamp":1785985865000},"score":1,"resource":{"primary":{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/10.1002\/jsfa.70730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":44,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/jsfa.70730"],"URL":"https:\/\/doi.org\/10.1002\/jsfa.70730","archive":["Portico"],"relation":{},"ISSN":["0022-5142","1097-0010"],"issn-type":[{"value":"0022-5142","type":"print"},{"value":"1097-0010","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"2025-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}