Ketones produced during fasting or a ketogenic diet promote muscle stem cell survival.

Fasting – the voluntary abstention from food and drink – is widely appreciated for its beneficial effects on human metabolism and healthspan. Evidence suggests that fasting flips a metabolic “switch,” liberating fat stores via fatty acid oxidation and ketone production. Findings from a recent study suggest that ketones induce a deep resting state in muscle stem cells, protecting them from future stressors.

Ketones are molecules produced by the liver during the breakdown of fatty acids. Ketone production occurs during periods of low food intake (fasting), ketogenic diets, starvation, or prolonged intense exercise. There are three types of ketones produced in the body: acetoacetate, beta-hydroxybutyrate, and acetone. Ketones are readily used as energy by a diverse array of cell types, including neurons.

Next, they examined muscle stem cells from both groups and found that the fasted animals' cells were smaller; had less mitochondrial content, RNA content, and basal oxygen consumption; and exhibited delayed cell division, compared to cells of non-fasting animals. Interestingly, the fasted animals' cells exhibited greater resilience to environmental stressors, such as oxidative stress and low nutrient availability.

Then the investigators treated muscle stem cells from the non-fasting mice with beta-hydroxybutyrate, a type of ketone. The cells exhibited similar resistance, likely due to beta-hydroxybutyrate’s actions as a histone deacetylase (HDAC) inhibitor. HDAC inhibition is associated with improved cellular resilience and longevity.

These findings suggest that ketones, particularly beta-hydroxybutyrate, induce a deep resting state in muscle stem cells, protecting them from future stressors. Learn more about beta-hydroxybutyrate in our overview article.

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