Cold activates a BH2 metabolic network promoting longevity and proteostasis.

Cold activates a BH2 metabolic network that promotes longevity and proteostasis in Caenorhabditis elegans, with increased BH2 synthesis in muscle being sufficient for these effects.

• Why it matters: Understanding how cold temperatures extend lifespan and improve health can reveal molecular targets for aging-related diseases. The mechanisms linking temperature to organismal health remain largely unknown.
• What they did: The study used a multi-tissue signaling approach in C. elegans, showing that cold upregulates CAT-4, increasing BH2 production, which is transported and converted into BH4 to support lifespan and prevent protein aggregation.
• The result: Elevating BH2 synthesis in muscle alone promotes longevity and reduces protein aggregation even at normal temperatures, and in human cells, BH2 or tyrosine supplementation decreases aggregation of disease-related proteins.