Ketone bodies: A double-edged sword for mammalian life span.
Issei TomitaHiroaki TsurutaMako Yasuda-YamaharaKosuke YamaharaShogo KuwagataYuki Tanaka-SasakiMasami Chin-KanasakiYukihiro FujitaEiichiro NishiHideki KatagiriHiroshi MaegawaShinji KumePublished in: Aging cell (2023)
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.
Keyphrases
- physical activity
- weight loss
- healthcare
- cardiovascular events
- public health
- risk factors
- cardiovascular disease
- high fat diet induced
- metabolic syndrome
- mental health
- magnetic resonance
- mouse model
- cognitive decline
- social media
- coronary artery disease
- magnetic resonance imaging
- climate change
- mild cognitive impairment