D-ß-hydroxybutyrate: an anti-aging ketone body

Edwards, Clare; Copes, Neil; Bradshaw, Patrick C.

doi:10.18632/oncotarget.3423

Cited by 15 publications

(15 citation statements)

References 7 publications

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“…Convincing arguments for a ketogenic diet to be the default treatment for diabetes are a decade old [ 13 ] and have continued to gain support since then [ 14 ]. Similar arguments are developing for obesity [ 10 , 11 ], neurodegenerative diseases [ 19 , 20 , 27 – 30 ], cardiovascular disease [ 15 – 17 ], cancer [ 18 – 26 ], and even aging [ 31 , 32 ]. Although the mechanisms through which a ketogenic diet may improve these conditions expand beyond mitochondrial function, the great extent to which nutritional ketosis increases reliance on mitochondrial metabolism strongly suggests that mitochondrial adaptation is a central factor.…”

Section: Discussionmentioning

confidence: 73%

Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

Miller

Villamena

Volek

2018

Journal of Nutrition and Metabolism

151

119

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Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS) and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β-hydroxybutyrate (BHB), which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations.

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Section: Discussionmentioning

confidence: 73%

Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

Miller

Villamena

Volek

2018

Journal of Nutrition and Metabolism

151

119

View full text Add to dashboard Cite

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“…Furthermore, in the RCT described herein, we found elevated b-hydroxybutyrate even during non-fasted conditions after 4 weeks of ADF. Increased b-hydroxybutyrate levels positively influence various parameters of health (Edwards et al, 2015) indirectly reduce blood pressure caused by high salt consumption (Chakraborty et al, 2018) and improve cerebral blood flow in aging brain upon CR (Lin et al, 2015).…”

Section: Perspectivementioning

confidence: 99%

Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans

et al. 2019

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Caloric restriction and intermittent fasting are known to prolong life-and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-tolean ratio, and increased b-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.

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“…Although the specific mechanisms by which lipid interventions affect lifespan are largely unknown, it is clear that different interventions exhibit disparate levels of overlap with canonical aging pathways, such as dietary restriction. For example, ß‐hydroxybutyrate does not extend life under dietary restriction in C. elegans , suggesting that this ketone body is a dietary restriction mimetic (Edwards et al, ). Similarly, the royal jelly component 10‐hydroxy‐2‐decenoic acid does not elongate life in eat‐2 C. elegans mutants, suggesting the mechanism of action for this fatty acid overlaps with dietary restriction (Honda et al, ).…”

Section: Lipid‐related Aging Mechanismsmentioning

confidence: 99%

The role of lipid metabolism in aging, lifespan regulation, and age‐related disease

2019

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An emerging body of data suggests that lipid metabolism has an important role to play in the aging process. Indeed, a plethora of dietary, pharmacological, genetic, and surgical lipid‐related interventions extend lifespan in nematodes, fruit flies, mice, and rats. For example, the impairment of genes involved in ceramide and sphingolipid synthesis extends lifespan in both worms and flies. The overexpression of fatty acid amide hydrolase or lysosomal lipase prolongs life in Caenorhabditis elegans, while the overexpression of diacylglycerol lipase enhances longevity in both C. elegans and Drosophila melanogaster. The surgical removal of adipose tissue extends lifespan in rats, and increased expression of apolipoprotein D enhances survival in both flies and mice. Mouse lifespan can be additionally extended by the genetic deletion of diacylglycerol acyltransferase 1, treatment with the steroid 17‐α‐estradiol, or a ketogenic diet. Moreover, deletion of the phospholipase A2 receptor improves various healthspan parameters in a progeria mouse model. Genome‐wide association studies have found several lipid‐related variants to be associated with human aging. For example, the epsilon 2 and epsilon 4 alleles of apolipoprotein E are associated with extreme longevity and late‐onset neurodegenerative disease, respectively. In humans, blood triglyceride levels tend to increase, while blood lysophosphatidylcholine levels tend to decrease with age. Specific sphingolipid and phospholipid blood profiles have also been shown to change with age and are associated with exceptional human longevity. These data suggest that lipid‐related interventions may improve human healthspan and that blood lipids likely represent a rich source of human aging biomarkers.

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D-ß-hydroxybutyrate: an anti-aging ketone body

Cited by 15 publications

References 7 publications

Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans

The role of lipid metabolism in aging, lifespan regulation, and age‐related disease

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