{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:55:35Z","timestamp":1790085335526,"version":"4.0.1"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["Moonshot R&D; Grant Number JPMJMS2023"],"award-info":[{"award-number":["Moonshot R&D; Grant Number JPMJMS2023"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H03353"],"award-info":[{"award-number":["21H03353"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H03128"],"award-info":[{"award-number":["22H03128"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","award":["grant to E.N."],"award-info":[{"award-number":["grant to E.N."]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Accumulating evidence suggests health benefits of ketone bodies, and especially for longevity. However, the precise role of endogenous ketogenesis in mammalian life span, and the safety and efficacy of the long\u2010term exogenous supplementation of ketone bodies remain unclear. In the present study, we show that a deficiency in endogenous ketogenesis, induced by whole\u2010body\n                    <jats:italic>Hmgcs2<\/jats:italic>\n                    deletion, shortens life span in mice, and that this is prevented by daily ketone body supplementation using a diet containing 1,3\u2010butanediol, a precursor of \u03b2\u2010hydroxybutyrate. Furthermore, feeding the 1,3\u2010butanediol\u2010containing diet from early in life increases midlife mortality in normal mice, but in aged mice it extends life span and prevents the high mortality associated with atherosclerosis in\n                    <jats:italic>ApoE<\/jats:italic>\n                    \u2010deficient mice. By contrast, an ad libitum low\u2010carbohydrate ketogenic diet markedly increases mortality. In conclusion, endogenous ketogenesis affects mammalian survival, and ketone body supplementation may represent a double\u2010edged sword with respect to survival, depending on the method of administration and health status.\n                  <\/jats:p>","DOI":"10.1111\/acel.13833","type":"journal-article","created":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T01:40:21Z","timestamp":1681522821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Ketone bodies: A double\u2010edged sword for mammalian life span"],"prefix":"10.1111","volume":"22","author":[{"given":"Issei","family":"Tomita","sequence":"first","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Tsuruta","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mako","family":"Yasuda\u2010Yamahara","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Yamahara","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Kuwagata","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Tanaka\u2010Sasaki","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Chin\u2010Kanasaki","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichiro","family":"Nishi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shiga University of Medical Science, Tsukinowa\u2010cho, Seta  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Katagiri","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Diabetes Tohoku University Graduate School of Medicine  2\u20101 Seiryo\u2010machi, Aoba\u2010ku Sendai Miyagi 980\u20108574 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Maegawa","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6937-9715","authenticated-orcid":false,"given":"Shinji","family":"Kume","sequence":"additional","affiliation":[{"name":"Department of Medicine Shiga University of Medical Science  Tsukinowa\u2010cho, Seta Otsu Shiga 520\u20102192 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