β-hydroxybutyrate and its metabolic effects on age-associated pathology

• Published in: Experimental & molecular medicine Vol. 52; no. 4; pp. 548 - 555
• Main Authors: Han, Young-Min, Ramprasath, Tharmarajan, Zou, Ming-Hui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2020; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 13; 45/61; 59; 631/80/304; 692/308/575; 96; 96/21; Age; Aging; Biomedical and Life Sciences; Biomedicine; By products; Cardiovascular diseases; Cell membranes; Clinical trials; Dietary restrictions; Fatty acids; High fat diet; Ketogenesis; Ketones; Low carbohydrate diet; Medical Biochemistry; Metabolism; Metabolites; Molecular Medicine; Molecular modelling; Neurodegenerative diseases; Review; Review Article; Stem Cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-020-0415-z

Aging is a universal process that renders individuals vulnerable to many diseases. Although this process is irreversible, dietary modulation and caloric restriction are often considered to have antiaging effects. Dietary modulation can increase and maintain circulating ketone bodies, especially β-hydroxybutyrate (β-HB), which is one of the most abundant ketone bodies in human circulation. Increased β-HB has been reported to prevent or improve the symptoms of various age-associated diseases. Indeed, numerous studies have reported that a ketogenic diet or ketone ester administration alleviates symptoms of neurodegenerative diseases, cardiovascular diseases, and cancers. Considering the potential of β-HB and the intriguing data emerging from in vivo and in vitro experiments as well as clinical trials, this therapeutic area is worthy of attention. In this review, we highlight studies that focus on the identified targets of β-HB and the cellular signals regulated by β-HB with respect to alleviation of age-associated ailments. Age-associated disease: Possible metabolic therapy Boosting levels of a byproduct of fatty acid breakdown may help alleviate the symptoms of age-associated health conditions. When the body is low on glucose, it breaks down fatty acids for energy, generating byproduct metabolites called ketones. The ketone β-hydroxybutyrate (β-HB) regulates cellular signaling and gene and protein expression. There are indications that ketogenic diets or ketone administration, which increase β-BH may prevent ageing-associated progression of illnesses like cardiovascular and neurodegenerative diseases and cancer. Young-min Han and co-workers at Georgia State University in Atlanta, USA, reviewed current understanding of β-BH and its molecular targets. β-BH is a potent metabolite small enough to filter through cell membranes and circulate throughout the body, including the brain, influencing signaling pathways. Further investigations into associated molecular mechanisms will verify the metabolite’s potential as a therapeutic agent.