{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:29:11Z","timestamp":1787005751828,"version":"build-2736575974"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,10,29]]},"abstract":"<jats:p>\n                    Caloric restriction extends life span in a variety of species, highlighting the importance of energy balance in aging. A new longevity gene,\n                    <jats:italic>Indy<\/jats:italic>\n                    (for\n                    <jats:italic>I'm not dead yet<\/jats:italic>\n                    ), which doubles the average life span of flies without a loss of fertility or physical activity, was postulated to extend life by affecting intermediary metabolism. We report that functional studies in\n                    <jats:italic>Xenopus<\/jats:italic>\n                    oocytes show INDY is a metabolite transporter that mediates the high-affinity, disulfonic stilbene-sensitive flux of dicarboxylates and citrate across the plasma membrane by a mechanism that is not coupled to Na\n                    <jats:sup>+<\/jats:sup>\n                    , K\n                    <jats:sup>+<\/jats:sup>\n                    , or Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    . Immunocytochemical studies localize INDY to the plasma membrane with most prominent expression in adult fat body, oenocytes, and the basolateral region of midgut cells and show that life-extending mutations in\n                    <jats:italic>Indy<\/jats:italic>\n                    reduce INDY expression. We conclude that INDY functions as a novel sodium-independent mechanism for transporting Krebs and citric acid cycle intermediates through the epithelium of the gut and across the plasma membranes of organs involved in intermediary metabolism and storage. The life-extending effect of mutations in\n                    <jats:italic>Indy<\/jats:italic>\n                    is likely caused by an alteration in energy balance caused by a decrease in INDY transport function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.222531899","type":"journal-article","created":{"date-parts":[[2002,10,29]],"date-time":"2002-10-29T12:24:11Z","timestamp":1035894251000},"page":"14315-14319","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":81,"title":["Functional characterization and immunolocalization of the transporter encoded by the life-extending gene\n                    <i>Indy<\/i>"],"prefix":"10.1073","volume":"99","author":[{"given":"Felix","family":"Knauf","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; Franz Volhard Clinic at the Max Delbr\u00fcck Center, HELIOS Kliniken-Berlin, Medical Faculty Charit\u00e9, Humboldt University, 14050 Berlin, Germany; and Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanka","family":"Rogina","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; Franz Volhard Clinic at the Max Delbr\u00fcck Center, HELIOS Kliniken-Berlin, Medical Faculty Charit\u00e9, Humboldt University, 14050 Berlin, Germany; and Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; Franz Volhard Clinic at the Max Delbr\u00fcck Center, HELIOS Kliniken-Berlin, Medical Faculty Charit\u00e9, Humboldt University, 14050 Berlin, Germany; and Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Aronson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; Franz Volhard Clinic at the Max Delbr\u00fcck Center, HELIOS Kliniken-Berlin, Medical Faculty Charit\u00e9, Humboldt University, 14050 Berlin, Germany; and Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Helfand","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; Franz Volhard Clinic at the Max Delbr\u00fcck Center, HELIOS Kliniken-Berlin, Medical Faculty Charit\u00e9, Humboldt University, 14050 Berlin, Germany; and Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,10,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(00)00084-X"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.2.1.435"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5499.2137"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.7.3397"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1994.sp003754"},{"key":"e_1_3_3_6_2","first-page":"F432","volume":"253","author":"Wright S. 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