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Exercise-induced β-hydroxybutyrate contributes to cognitive improvement in aging mice
Lian Wang1, Liwei Mao1, Danlin Zhu2
1Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China; Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Exercise boosts brain health in aging mice by increasing beta-hydroxybutyrate (β-HB). This ketone body, either from exercise or supplements, enhances cognition and may combat brain aging.
Area of Science:
- Neuroscience
- Metabolism
- Aging Research
Background:
- Aging significantly contributes to cognitive decline and neurodegeneration.
- Current interventions for aging-related neuronal dysfunction are limited.
- Beta-hydroxybutyrate (β-HB), a ketone body, serves as an energy source and signaling molecule during fasting or exercise.
Purpose of the Study:
- To investigate the impact of exercise-induced and exogenous β-HB on cognitive function in aging mice.
- To explore the role of endogenous β-HB metabolism using BDH1 knockout mice.
- To examine the in vitro effects of GPR109A knockdown on β-HB signaling pathways.
Main Methods:
- Assessed cognitive performance in aging mice following exercise or β-HB supplementation.
- Utilized 3-hydroxybutyrate dehydrogenase 1 (BDH1) knockout mice to study endogenous β-HB metabolism.
- Investigated β-HB's effect on GPR109A and PPARγ activation in vitro.
Main Results:
- Exercise increased circulating β-HB and improved cognitive outcomes in aging mice.
- Exogenous β-HB supplementation replicated these cognitive benefits.
- BDH1 deficiency impaired β-HB production and reduced cognitive improvements.
- GPR109A knockdown inhibited β-HB-mediated PPARγ activation and neuroprotective signaling.
Conclusions:
- The β-HB/GPR109A-PPARγ pathway is crucial for exercise-induced cognitive enhancement in aging.
- β-HB shows potential as a therapeutic agent to mitigate brain aging and cognitive decline.
