Ketone bodies: A double-edged sword for mammalian life span.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford, UK : Wiley-Blackwell
      Original Publication: Oxford, UK : Blackwell Pub., c2002-
    • Subject Terms:
      Ketone Bodies* ; Longevity*; Mice ; Animals ; Butylene Glycols ; 3-Hydroxybutyric Acid ; Mammals
    • Abstract:
      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-term exogenous supplementation of ketone bodies remain unclear. In the present study, we show that a deficiency in endogenous ketogenesis, induced by whole-body Hmgcs2 deletion, shortens life span in mice, and that this is prevented by daily ketone body supplementation using a diet containing 1,3-butanediol, a precursor of β-hydroxybutyrate. Furthermore, feeding the 1,3-butanediol-containing 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 ApoE-deficient mice. By contrast, an ad libitum low-carbohydrate ketogenic diet markedly increases mortality. In conclusion, endogenous ketogenesis affects mammalian survival, and ketone body supplementation may represent a double-edged sword with respect to survival, depending on the method of administration and health status.
      (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
    • References:
      Cell Metab. 2016 Aug 9;24(2):256-68. (PMID: 27475046)
      Circulation. 2019 Apr 30;139(18):2129-2141. (PMID: 30884964)
      Cell Metab. 2019 Sep 3;30(3):462-476.e6. (PMID: 31471173)
      Cell. 2019 Aug 22;178(5):1115-1131.e15. (PMID: 31442404)
      N Engl J Med. 1970 Mar 19;282(12):668-75. (PMID: 4915800)
      N Engl J Med. 2003 May 22;348(21):2082-90. (PMID: 12761365)
      Cell Metab. 2017 Sep 5;26(3):547-557.e8. (PMID: 28877458)
      J Clin Invest. 2014 Dec;124(12):5175-90. (PMID: 25347470)
      Aging Cell. 2023 Jun;22(6):e13833. (PMID: 37060184)
      J Clin Invest. 1974 Feb;53(2):508-15. (PMID: 11344564)
      Cell Metab. 2017 Sep 5;26(3):539-546.e5. (PMID: 28877457)
      Cell Metab. 2020 Sep 1;32(3):404-419.e6. (PMID: 32726607)
      Aging Cell. 2021 Dec;20(12):e13510. (PMID: 34719871)
      Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):6170-6177. (PMID: 32127481)
      Nutrients. 2021 Jun 16;13(6):. (PMID: 34208742)
      Cell Metab. 2019 Dec 3;30(6):1007-1023.e5. (PMID: 31631001)
    • Contributed Indexing:
      Keywords: Hmgcs2; ketone body; longevity; low-carbohydrate ketogenic diet
    • Accession Number:
      0 (Ketone Bodies)
      3XUS85K0RA (1,3-butylene glycol)
      0 (Butylene Glycols)
      TZP1275679 (3-Hydroxybutyric Acid)
    • Publication Date:
      Date Created: 20230415 Date Completed: 20230615 Latest Revision: 20230627
    • Publication Date:
      20240105
    • Accession Number:
      PMC10265173
    • Accession Number:
      10.1111/acel.13833
    • Accession Number:
      37060184