{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:08:57Z","timestamp":1792811337237,"version":"4.5.0"},"reference-count":48,"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":[[1998,10,27]]},"abstract":"<jats:p>\n                    Low caloric intake (caloric restriction) can lengthen the life span of a wide range of animals and possibly even of humans. To understand better how caloric restriction lengthens life span, we used genetic methods and criteria to investigate its mechanism of action in the nematode\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    . Mutations in many genes (\n                    <jats:italic>eat<\/jats:italic>\n                    genes) result in partial starvation of the worm by disrupting the function of the pharynx, the feeding organ. We found that most\n                    <jats:italic>eat<\/jats:italic>\n                    mutations significantly lengthen life span (by up to 50%). In\n                    <jats:italic>C. elegans,<\/jats:italic>\n                    mutations in a number of other genes that can extend life span have been found. Two genetically distinct mechanisms of life span extension are known: a mechanism involving genes that regulate dauer formation (\n                    <jats:italic>age-1, daf-2, daf-16<\/jats:italic>\n                    , and\n                    <jats:italic>daf-28<\/jats:italic>\n                    ) and a mechanism involving genes that affect the rate of development and behavior (\n                    <jats:italic>clk-1, clk-2, clk-3<\/jats:italic>\n                    , and\n                    <jats:italic>gro-1<\/jats:italic>\n                    ). We find that the long life of\n                    <jats:italic>eat-2<\/jats:italic>\n                    mutants does not require the activity of DAF-16 and that\n                    <jats:italic>eat-2; daf-2<\/jats:italic>\n                    double mutants live even longer than extremely long-lived\n                    <jats:italic>daf-2<\/jats:italic>\n                    mutants. These findings demonstrate that food restriction lengthens life span by a mechanism distinct from that of dauer-formation mutants. In contrast, we find that food restriction does not further increase the life span of long-lived\n                    <jats:italic>clk-1<\/jats:italic>\n                    mutants, suggesting that\n                    <jats:italic>clk-1<\/jats:italic>\n                    and caloric restriction affect similar processes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.22.13091","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"13091-13096","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":884,"title":["The genetics of caloric restriction in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1073","volume":"95","author":[{"given":"Bernard","family":"Lakowski","sequence":"first","affiliation":[{"name":"Department of Biology, McGill University, 1205 Dr. Penfield Avenue, Montr\u00e9al, Qu\u00e9bec, Canada H3A 1B1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Hekimi","sequence":"additional","affiliation":[{"name":"Department of Biology, McGill University, 1205 Dr. Penfield Avenue, Montr\u00e9al, Qu\u00e9bec, Canada H3A 1B1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,10,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/10.1.63"},{"key":"e_1_3_3_2_2","volume-title":"The Retardation of Aging and Disease by Dietary Restriction.","author":"Weindruch R K","year":"1988","unstructured":"R K Weindruch, R L Walford The Retardation of Aging and Disease by Dietary Restriction. 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