Cold-activated BH2 metabolic network extends lifespan and clears toxic protein aggregates
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A Nature study shows that cold triggers a metabolic circuit with anti-aging effects. In C. elegans, low temperatures drive synthesis of BH2 in muscle through the enzyme CAT-4. BH2 then travels to distant tissues, where it is converted to BH4 and used by PAH-1 to make the amino acid tyrosine. This pathway extends lifespan and improves protein quality control across tissues. Supplementing BH2 or tyrosine also suppressed aggregation of toxic proteins, including polyQ74, TDP-43(A382T) and FUS(P525L), in human HEK293 cells and in motor neurons derived from ALS patient iPSCs. The results link cold exposure, metabolism and proteostasis, with implications for neurodegenerative disease research.
Written by a model from the reports · updated 3 hours ago
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- NaturePickCold activates a BH2 metabolic network promoting longevity and proteostasis
In C. elegans, cold drives BH2 synthesis in muscle via CAT-4; BH2 is transported to distal tissues, reduced to BH4, and used by PAH-1 to synthesize tyrosine, extending lifespan and improving cross-tissue proteostasis. Supplementation with BH2 or tyrosine likewise suppresses aggregation of toxic proteins including polyQ74, TDP-43(A382T) and FUS(P525L) in HEK293 cells and ALS iPSC-derived motor neurons.
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