Researchers have discovered that betaine, a metabolite produced by the kidneys, mimics many anti-aging benefits of exercise. The study, published in Cell, shows how sustained physical activity triggers a surge in betaine to reduce inflammation and rejuvenate immune cells. Oral betaine supplementation alone replicated these effects in animal models.
A new study from the Chinese Academy of Sciences and Xuanwu Hospital Capital Medical University reveals the mechanisms behind exercise's anti-aging effects, pinpointing betaine as a key player. Published in the journal Cell on October 10, 2025 (volume 188, issue 19, pages 5403), the research used multiomics analysis to track genes, proteins, metabolites, and gut bacteria in 13 healthy men.
The team compared participants at rest, after a single 5 km run, and following a 25-day running program. Short-term intense exercise induced temporary inflammation and metabolic stress, explaining the 'exercise paradox' where acute activity causes harm but chronic training promotes health. Over the longer period, the kidneys ramped up betaine production via the enzyme CHDH, sending anti-aging signals body-wide.
Betaine, naturally found in beets and spinach and produced endogenously, restored metabolic balance, improved gut bacteria, boosted antioxidants, and reversed age-related changes in T cells by stabilizing DNA and altering epigenetic marks like reduced ETS1 expression. In older mice, betaine supplementation enhanced cognition, reduced depressive-like behavior, and lowered inflammation by binding to and inhibiting the kinase TBK1, thereby suppressing IRF3/NF-κB pathways and 'inflammaging.'
Short-term exercise activates survival pathways like IL-6 and corticosterone, while long-term training engages the kidney-betaine-TBK1 system for rejuvenation. As betaine is safe, it offers potential for those unable to exercise. 'This redefines "exercise as medicine,"' says co-corresponding author Dr. Liu Guang-Hui. 'This study gives us a fresh way to turn how our body works into something we can target with chemicals. It opens the door to geroprotective treatments that can tweak how multiple organs work together.'