Ketogenic Diet Reduces Age-Induced Chronic Neuroinflammation in Mice

Area of Science:

• Neuroscience
• Metabolic pathways
• Inflammation research

Background:

• Beta-hydroxybutyrate (BHB) is an energy metabolite produced during fasting or exercise.
• Previous studies show cyclic ketogenic diets (KD) reduce mortality and improve memory in aging mice.
• Mechanisms of BHB's effects on brain aging and inflammation are not fully understood.

Purpose of the Study:

• Investigate the impact of KD and BHB on gene expression and neuroinflammation in aging mice.
• Elucidate the role of BHB in regulating inflammatory responses in primary brain cells.

Main Methods:

• Bulk RNA-sequencing (RNA-Seq) on whole brains of mice fed KD for one week or 14 months.
• RNA-Seq analysis of human primary microglia, astrocytes, and neurons.
• In vitro experiments using mouse primary microglia to study BHB's effect on lipopolysaccharide (LPS)-induced inflammation.

Main Results:

• One-week KD increased inflammatory gene expression, while 14-month cyclic KD reduced age-induced neuroinflammation.
• BHB alone induced mild inflammation in human brain cells but inhibited LPS-induced inflammation in microglia.
• BHB's anti-inflammatory effect in microglia was observed in vitro, potentially linked to an acidic milieu.

Conclusions:

• Long-term cyclic KD reduces neuroinflammation in aging mice.
• BHB can attenuate microglial inflammatory responses to stimuli like LPS.
• BHB's modulation of neuroinflammation may contribute to the benefits of KD in aging brains.