{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T05:00:36Z","timestamp":1755925236270},"reference-count":11,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T00:00:00Z","timestamp":1137024000000},"content-version":"vor","delay-in-days":590,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Mutations that extend life span in <jats:italic>C. elegans<\/jats:italic> suggest that the insulin\/IGF\u20101 signaling (IS) pathway may play a key role in retarding aging and extending life span by caloric restriction (CR). To evaluate this hypothesis, male rats were subjected to either AL (<jats:italic>ad libitum<\/jats:italic>) or CR (40% from AL) for 2 and 25 months, and then the effects of CR on the early events in the IS pathway in liver and muscle were assessed. The results indicated that aging was accompanied by a significant decline in insulin receptor tyrosine phosphorylation (pY\u2010IR) upon insulin stimulation in both tissues, which was correlated with a significant increase in the activity of protein tyrosine phosphatase 1B (PTP\u20101B). However, these alterations with age were attenuated by 25CR. Parallel changes observed in liver mRNA of CR rats were upregulated insulin receptor (IR), IGF\u20101R and IRS\u20101, but increased expression of IR mRNA was dissociated with the IR protein in 25CR rats. The expression of liver mRNAs involved in lipid metabolism was also analyzed. In contrast to 25AL rats, the expression of mRNAs for PPARs (\u03b1, \u03b4, and \u03b3) was significantly increased in 25CR rats. SREBP\u20101c and fatty acid synthase were reduced, and other genes were increased, including hormone\u2010sensitive lipase and PGC\u20101 by CR. The data suggest that the normal function of insulin receptor in liver and muscle is required for successful aging. An altered expression of transcription of a number of genes involved in lipid metabolism may also contribute to modulation of the IS pathway by CR.<\/jats:p>","DOI":"10.1196\/annals.1297.082","type":"journal-article","created":{"date-parts":[[2004,7,10]],"date-time":"2004-07-10T21:39:14Z","timestamp":1089495554000},"page":"448-452","source":"Crossref","is-referenced-by-count":14,"title":["Caloric Restriction Modulates Early Events in Insulin Signaling in Liver and Skeletal Muscle of Rat"],"prefix":"10.1111","volume":"1019","author":[{"given":"MIN","family":"ZHU","sequence":"first","affiliation":[]},{"given":"RAFAEL","family":"DE CABO","sequence":"additional","affiliation":[]},{"given":"MARK A.","family":"LANE","sequence":"additional","affiliation":[]},{"given":"DONALD K.","family":"INGRAM","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2006,1,12]]},"reference":[{"key":"e_1_2_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(00)00084-X"},{"key":"e_1_2_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb05660.x"},{"key":"e_1_2_4_4_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.42.12.1809"},{"key":"e_1_2_4_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.5.2240"},{"key":"e_1_2_4_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.273.5.E1014"},{"key":"e_1_2_4_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3270139"},{"key":"e_1_2_4_8_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006868409841"},{"key":"e_1_2_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.15.5479-5489.2000"},{"key":"e_1_2_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00305-1"},{"key":"e_1_2_4_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1544"},{"key":"e_1_2_4_12_2","doi-asserted-by":"crossref","unstructured":"Zhu M. J. Miura L.X. Lu et al.2004. Circulating adiponectin levels increase in rats on caloric restriction: the potential for insulin sensitization. Exp. Gerontol. In press.","DOI":"10.1016\/j.exger.2004.03.024"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1297.082","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1297.082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T21:09:31Z","timestamp":1696799371000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1297.082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1196\/annals.1297.082"],"URL":"https:\/\/doi.org\/10.1196\/annals.1297.082","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6]]}}}