{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:49:23Z","timestamp":1792788563894,"version":"4.5.0"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangzhou Science, Technology, and Innovation Commission","award":["2025B03J0102"],"award-info":[{"award-number":["2025B03J0102"]}],"id":[{"id":"https:\/\/ror.org\/05t4nb462","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Guangzhou Science, Technology, and Innovation Commission","award":["2024A03J0144"],"award-info":[{"award-number":["2024A03J0144"]}],"id":[{"id":"https:\/\/ror.org\/05t4nb462","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Hallmarks of aging are highly variable among individuals, and sexual dimorphism may contribute to these differences. However, the details are unclear.The gut-metabolism axisin naturally aging wild-type and\n                    <jats:italic>Nrf2<\/jats:italic>\n                    knockout (KO) mouse models was investigated. In this study, intraperitoneal glucose tolerance tests were performed on 12- and 48-week-old wild-type and\n                    <jats:italic>Nrf2<\/jats:italic>\n                    KO mice to assess glucose tolerance. Serum total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein levels were measured using biochemicaltest kits. The estradiol and testosterone levels in the serum were detected using enzyme-linked immunosorbent assays. Liver and adipose tissue morphology were examined using hematoxylin and eosin staining, and gut microbiota composition was analyzed using 16S rDNA sequencing of fecal samples.The results showed that glucose tolerance was significantly impaired in aging male\n                    <jats:italic>Nrf2<\/jats:italic>\n                    KO mice, and lipid accumulation in hepatic and adipose tissues increased in aging wild-type (WT) miceandaging\n                    <jats:italic>Nrf2<\/jats:italic>\n                    KO mice of both sexescompared with that in their young counterparts.Aged miceand\n                    <jats:italic>Nrf2<\/jats:italic>\n                    KO mice exhibited divergent responses in their serum lipid profiles.Notably, female\n                    <jats:italic>Nrf2<\/jats:italic>\n                    KO mice showed a significantly lower\u03b1-diversity in gut bacterial composition, compared with both male\n                    <jats:italic>Nrf2<\/jats:italic>\n                    KO mice and female WT controls.In conclusion, the resultsindicatethat aging and\n                    <jats:italic>Nrf2<\/jats:italic>\n                    deficiency promoted weight gain and tissue lipid accumulation in both sexes but elicited sex-dimorphic differences in blood glucose stability, microbiota composition, and the magnitude of adiposity. Therefore, sex is an important factor contributing to age-related variations in gut microbiota and metabolism.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0357015","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:42:01Z","timestamp":1790012521000},"page":"e0357015","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-based differences in the gut-metabolism axis in aging and Nrf2-deficient mice"],"prefix":"10.1371","volume":"21","author":[{"given":"Si","family":"Yang","sequence":"first","affiliation":[{"name":"Guangzhou Medical University","place":["Guangzhou, China"],"department":["Department of Obstetrics and Gynecology, the Third Affiliated Hospital"]},{"name":"Guangzhou Medical University","place":["Guangzhou, China"],"department":["Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, the T..."]},{"name":"BioResource Research Center, the Third Affiliated Hospital of Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Foshan Women and Children Hospital Affiliated to Guangdong Medical University","place":["Foshan, China"],"department":["Department of Gynecology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University","place":["Guangzhou, China"],"department":["Department of Obstetrics and Gynecology, the Third Affiliated Hospital"]},{"name":"Guangzhou Medical University","place":["Guangzhou, China"],"department":["Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, the T..."]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University","place":["Guangzhou, China"],"department":["Department of Obstetrics and Gynecology, the Third Affiliated Hospital"]},{"name":"Guangzhou Medical University","place":["Guangzhou, China"],"department":["Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, the 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