{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:18:48Z","timestamp":1789172328354,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,9]]},"group-title":"Physiology","reference-count":77,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"European Research Council","award":["ERC-2023-SyG, 101118919"],"award-info":[{"award-number":["ERC-2023-SyG, 101118919"]}]},{"name":"The Hevolution Foundation","award":["HF-GRO-23-1199212-35"],"award-info":[{"award-number":["HF-GRO-23-1199212-35"]}]},{"DOI":"10.13039\/501100005677","name":"DJCLS","doi-asserted-by":"crossref","award":["04 R\/2023"],"award-info":[{"award-number":["04 R\/2023"]}],"id":[{"id":"10.13039\/501100005677","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005972","name":"The Deutsche Krebshilfe","doi-asserted-by":"crossref","award":["70114555"],"award-info":[{"award-number":["70114555"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Bundesministerium f\u00fcr Forschung, Technologie und Raumfahrt (BMFTR) X-AGE project","award":["02NUK105B"],"award-info":[{"award-number":["02NUK105B"]}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["U54AG079759"],"award-info":[{"award-number":["U54AG079759"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"crossref","award":["Yale University Intramural Funding"],"award-info":[{"award-number":["Yale University Intramural Funding"]}],"id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Elevated sulfur-containing amino acids (SAA; methionine and cystine) are linked to human mortality. While methionine restriction (MR) extends lifespan in animals, it is often ignored that traditional longevity-promoting MR diets also lack cystine. When dietary cystine is eliminated, host redirects substrates from methionine cycle and generates cysteine via cystathionine \u03b3-lyase (CTH) in transsulfuration pathway, leaving it unclear which SAA controls aging. Here, we show that selective cysteine restriction in\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  enhanced lifespan and stress survival independently of methionine. Notably, cysteine-free diets (methionine-replete or restricted) in\n                  <jats:italic>Cth-<\/jats:italic>\n                  deficient mice induced pro-metabolic effects, whereas MR with normal cysteine was ineffective. Sustained 70% cysteine reduction in aged\n                  <jats:italic>\n                    Cth\n                    <jats:sup>-<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>\/-<\/jats:sup>\n                  mice reprogrammed the immunometabolic axis, conferring healthspan benefits. Thus, lowering cysteine while keeping the methionine pool intact enhances healthy lifespan.\n                <\/jats:p>","DOI":"10.64898\/2026.09.04.749519","type":"posted-content","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:55:11Z","timestamp":1789012511000},"source":"Crossref","is-referenced-by-count":0,"title":["Cysteine reduction rather than methionine restriction promotes immunometabolic fitness to confer survival benefit in aging"],"prefix":"10.64898","author":[{"given":"Lucie","family":"Orliaguet","sequence":"first","affiliation":[{"name":"Department of Pathology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Immunobiology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Comparative Medicine, Yale School of Medicine; New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Immunobiology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Comparative Medicine, Yale School of Medicine; New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush","family":"Gupta","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne; Cologne 50931, Germany"},{"name":"Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University and University Hospital of Cologne, Cologne 50931, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine; New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjiu","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Immunobiology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Comparative Medicine, Yale School of Medicine; New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine; New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carisa","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Hee","family":"Youm","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Immunobiology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Comparative Medicine, Yale School of Medicine; New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Dlugos","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Immunobiology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Comparative Medicine, Yale School of Medicine; New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Immunobiology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Comparative Medicine, Yale School of Medicine; New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Yale Center for Research on Aging, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim N.","family":"Artyomov","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Kluger","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Yale Center for Research on Aging, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute for Genome Stability in Aging and Disease, Medical Faculty, University and University Hospital of Cologne; Cologne 50931, Germany"},{"name":"Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University and University Hospital of Cologne, Cologne 50931, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwa Deep","family":"Dixit","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Immunobiology, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Department of Comparative Medicine, Yale School of Medicine; New Haven, CT 06520, USA"},{"name":"Yale Center for Research on Aging, Yale School of Medicine, New Haven, CT 06520, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091117050420000_2026.09.04.749519v1.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.06.070186.001143"},{"key":"2026091117050420000_2026.09.04.749519v1.2","doi-asserted-by":"publisher","DOI":"10.1097\/00075197-200201000-00015"},{"key":"2026091117050420000_2026.09.04.749519v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/srep26074"},{"key":"2026091117050420000_2026.09.04.749519v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4222"},{"key":"2026091117050420000_2026.09.04.749519v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-025-01297-8"},{"key":"2026091117050420000_2026.09.04.749519v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08996-y"},{"key":"2026091117050420000_2026.09.04.749519v1.7","doi-asserted-by":"publisher","DOI":"10.2337\/db16-1212"},{"key":"2026091117050420000_2026.09.04.749519v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17818-w"},{"key":"2026091117050420000_2026.09.04.749519v1.9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00838.2009"},{"key":"2026091117050420000_2026.09.04.749519v1.10","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/123.2.269"},{"key":"2026091117050420000_2026.09.04.749519v1.11","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.8.15.8001743"},{"key":"2026091117050420000_2026.09.04.749519v1.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2005.00152.x"},{"key":"2026091117050420000_2026.09.04.749519v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glp051"},{"key":"2026091117050420000_2026.09.04.749519v1.14","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13739"},{"key":"2026091117050420000_2026.09.04.749519v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2026.04.025"},{"key":"2026091117050420000_2026.09.04.749519v1.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1514511113"},{"key":"2026091117050420000_2026.09.04.749519v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.05.011"},{"key":"2026091117050420000_2026.09.04.749519v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.12.016"},{"key":"2026091117050420000_2026.09.04.749519v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2297"},{"key":"2026091117050420000_2026.09.04.749519v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.09.007"},{"key":"2026091117050420000_2026.09.04.749519v1.21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049452"},{"key":"2026091117050420000_2026.09.04.749519v1.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.16.7540"},{"key":"2026091117050420000_2026.09.04.749519v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2024.102026"},{"key":"2026091117050420000_2026.09.04.749519v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-025-00921-2"},{"key":"2026091117050420000_2026.09.04.749519v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04518-2"},{"key":"2026091117050420000_2026.09.04.749519v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2856-x"},{"key":"2026091117050420000_2026.09.04.749519v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2025.102252"},{"key":"2026091117050420000_2026.09.04.749519v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108624"},{"key":"2026091117050420000_2026.09.04.749519v1.29","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ady0415"},{"key":"2026091117050420000_2026.09.04.749519v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2026.04.020"},{"key":"2026091117050420000_2026.09.04.749519v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00652-w"},{"key":"2026091117050420000_2026.09.04.749519v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32552-1"},{"key":"2026091117050420000_2026.09.04.749519v1.33","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0436"},{"key":"2026091117050420000_2026.09.04.749519v1.34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133518"},{"key":"2026091117050420000_2026.09.04.749519v1.35","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00263.2007"},{"key":"2026091117050420000_2026.09.04.749519v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.08.004"},{"key":"2026091117050420000_2026.09.04.749519v1.37","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf1119"},{"key":"2026091117050420000_2026.09.04.749519v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101468"},{"key":"2026091117050420000_2026.09.04.749519v1.39","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-019-00076-0"},{"key":"2026091117050420000_2026.09.04.749519v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/nature08980"},{"key":"2026091117050420000_2026.09.04.749519v1.41","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M010215"},{"key":"2026091117050420000_2026.09.04.749519v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01046-3"},{"key":"2026091117050420000_2026.09.04.749519v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2499-y"},{"key":"2026091117050420000_2026.09.04.749519v1.44","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.108825"},{"key":"2026091117050420000_2026.09.04.749519v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50454-2"},{"key":"2026091117050420000_2026.09.04.749519v1.46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI197556"},{"key":"2026091117050420000_2026.09.04.749519v1.47","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13629"},{"key":"2026091117050420000_2026.09.04.749519v1.48","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12400"},{"key":"2026091117050420000_2026.09.04.749519v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(04)63006-7"},{"key":"2026091117050420000_2026.09.04.749519v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.06.018"},{"key":"2026091117050420000_2026.09.04.749519v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-025-01236-7"},{"key":"2026091117050420000_2026.09.04.749519v1.52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74915"},{"key":"2026091117050420000_2026.09.04.749519v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29499-8"},{"key":"2026091117050420000_2026.09.04.749519v1.54","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e32834d199f"},{"key":"2026091117050420000_2026.09.04.749519v1.55","doi-asserted-by":"publisher","DOI":"10.1126\/science.ady0832"},{"key":"2026091117050420000_2026.09.04.749519v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.12.035"},{"key":"2026091117050420000_2026.09.04.749519v1.57","doi-asserted-by":"publisher","DOI":"10.1051\/medsci\/20031967725"},{"key":"2026091117050420000_2026.09.04.749519v1.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2014.04.002"},{"key":"2026091117050420000_2026.09.04.749519v1.59","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2017.0017"},{"key":"2026091117050420000_2026.09.04.749519v1.60","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(1999)004<0235:DOOSRI>2.3.CO;2"},{"key":"2026091117050420000_2026.09.04.749519v1.61","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D023788"},{"key":"2026091117050420000_2026.09.04.749519v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0439-x"},{"key":"2026091117050420000_2026.09.04.749519v1.63","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2026091117050420000_2026.09.04.749519v1.64","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"2026091117050420000_2026.09.04.749519v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3820"},{"key":"2026091117050420000_2026.09.04.749519v1.66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177459"},{"key":"2026091117050420000_2026.09.04.749519v1.67","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.7563.2"},{"key":"2026091117050420000_2026.09.04.749519v1.68","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026091117050420000_2026.09.04.749519v1.69","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty895"},{"key":"2026091117050420000_2026.09.04.749519v1.70","doi-asserted-by":"publisher","DOI":"10.1101\/060012"},{"key":"2026091117050420000_2026.09.04.749519v1.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100612"},{"key":"2026091117050420000_2026.09.04.749519v1.72","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aec9991"},{"key":"2026091117050420000_2026.09.04.749519v1.73","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"2026091117050420000_2026.09.04.749519v1.74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009290"},{"key":"2026091117050420000_2026.09.04.749519v1.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"2026091117050420000_2026.09.04.749519v1.76","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"2026091117050420000_2026.09.04.749519v1.77","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.04.749519","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:05:16Z","timestamp":1789171516000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.04.749519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":77,"URL":"https:\/\/doi.org\/10.64898\/2026.09.04.749519","relation":{},"subject":[],"published":{"date-parts":[[2026,9,9]]},"subtype":"preprint"}}