Ketone bodies: A double-edged sword for mammalian life span.
Hmgcs2
ketone body
longevity
low-carbohydrate ketogenic diet
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
30
01
2023
accepted:
24
03
2023
medline:
15
6
2023
pubmed:
16
4
2023
entrez:
15
4
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37060184
doi: 10.1111/acel.13833
pmc: PMC10265173
doi:
Substances chimiques
Ketone Bodies
0
1,3-butylene glycol
3XUS85K0RA
Butylene Glycols
0
3-Hydroxybutyric Acid
TZP1275679
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13833Informations de copyright
© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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