The glycolytic metabolite phosphoenolpyruvate restricts cGAS-driven inflammation to promote healthy aging - PubMed
3 days ago
- #aging
- #inflammation
- #metabolism
- Phosphoenolpyruvate (PEP), a glycolytic metabolite, restricts cGAS-driven inflammation to promote healthy aging.
- Longitudinal studies in mice and humans show a biphasic PEP trajectory: initial accumulation followed by decline.
- Blocking PEP accumulation worsens inflammation and accelerates aging, while PEP administration promotes healthy aging.
- PEP competitively binds to cGAS, inhibiting the cGAS-STING pathway, reducing inflammation.
- High PEP levels in aged humans correlate with lower inflammation and healthier traits.
- PEP alleviates neuroinflammation and improves cognitive function in an Alzheimer's disease mouse model.
- PEP accumulation is identified as an evolutionarily conserved geroprotective mechanism.