Fasting, caloric restriction, and exercise improve lifespan and healthspan through their effects on distinct metabolic pathways. In particular the ketone body Beta-hydroxybutyrate (β-HB), which is elevated by these interventions in response to low glucose availability, has recently been demonstrated to have diverse signaling functions including regulating inflammation and inhibiting the activity of histone deacetylases (HDACs).

Ketogenic diets elevate blood levels of β-HB and may enhance longevity and healthspan. Male mice fed a cyclical ketogenic diet (CKD) alternated weekly with a control (non-ketogenic diet) experienced a reduction in midlife mortality but not maximal lifespan, and maintained cognitive performance and memory with age; benefits associated with distinct gene expression patterns including protein acetylation, PPAR-alpha upregulation, and downregulation of glucose metabolism, insulin signaling, fatty acid synthesis, and TOR activity. These patterns are similar to those activated by fasting, and suggests that β-HB may activate a youthful genetic program and prevent age-related memory decline.

View the full paper here at Cell Metabolism.