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This study demonstrates that a 10\u2010h TRF window significantly mitigates cardiac aging phenotypes including fibrosis, mitochondrial dysfunction, and senescence\u2010associated secretory phenotype in prediabetic mice, whereas these protective effects are largely blunted at the diabetic stage, despite improving systemic metabolism in both prediabetic and diabetic models. Mechanistically, TRF acts as a chronotherapeutic cue that restores the diurnal oscillations of short\u2010chain fatty acid (SCFA)\u2010producing gut microbiota. These rhythmic SCFAs serve as peripheral \u201cmetabolic zeitgebers\u201d that resynchronize cardiac diurnal rhythms autophagy. In vitro, SCFAs enhance autophagic flux and preserve mitochondrial integrity in senescent cardiomyocytes. Crucially, the cardioprotective benefits of TRF are largely abolished in p62\u2010deficient mice, identifying p62\u2010dependent autophagy and mitochondrial homeostasis as a key molecular mechanism underlying TRF efficacy. In overt diabetes, the loss of TRF\u2010mediated protection is attributed to a profound \u201cmetabolic rigidity\u201d that prevents restoration of autophagic rhythmicity. Overall, our findings reveal that TRF prevents cardiac aging by entraining the gut microbiota\u2013SCFA\u2013cardiac p62 axis during the prediabetic stage, highlighting a critical metabolic window for dietary intervention.<\/jats:p>","DOI":"10.1002\/mco2.70910","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T05:29:22Z","timestamp":1786339762000},"source":"Crossref","is-referenced-by-count":1,"title":["Time\u2010Restricted Feeding Prevents Cardiac Aging by Entraining Gut Microbiota Clock and Promoting Diurnal Rhythm Autophagy in Prediabetic Mice"],"prefix":"10.1002","volume":"7","author":[{"given":"Yuying","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiology The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Xiangya Hospital of Central South University  Changsha China"},{"name":"Department of Blood Transfusion The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunxi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Xiangya Hospital of Central South University  Changsha China"},{"name":"Department of Blood Transfusion The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hejun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Xiangya Hospital of Central South University  Changsha China"},{"name":"Department of Blood Transfusion The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyao","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Xiangya Hospital of Central South University  Changsha China"},{"name":"Department of Blood Transfusion The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5802-2910","authenticated-orcid":false,"given":"Shi","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.246876"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01378-8"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311586"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.305250"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.06.013"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273094"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab027"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12123770"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2023.107412"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.04.010"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.11.004"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","unstructured":"P.Boyd S. 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