Nature: Cold Triggers Muscles to Produce Protective Metabolite BH2
18:51 22 October, 2026Moderate cold exposure can effectively extend lifespan and slow age-related changes in animals. However, exactly how low temperatures trigger these beneficial effects at the molecular level has remained largely unclear. Now, scientists at the University of Cologne have deciphered a signaling system regulated by metabolites across different tissues. The findings were published in the journal Nature.
In a study involving the nematode Caenorhabditis elegans, the researchers demonstrated a link between cold exposure, increased lifespan and proteostasis — the maintenance of protein homeostasis. They found that muscles act as a “central factory,” producing the metabolite dihydrobiopterin (BH2).
BH2 is then transported to other tissues, where it is used to produce the amino acid tyrosine. This metabolic pathway helps strengthen the cellular machinery responsible for maintaining functional proteins.
The scientists also confirmed their findings in cell models of Huntington’s disease and amyotrophic lateral sclerosis (ALS), age-related neurodegenerative disorders characterized by the accumulation of damaged proteins.
“We are excited to show that moderately cold temperatures trigger the substantial production of a specific metabolite, BH2, which is synthesized, stored and then released by muscle tissue. BH2 is subsequently directed to other parts of the body, where it helps maintain protein homeostasis and tissue health during aging,” explained study leader David Vilchez.
According to Vilchez, the findings suggest that targeting a single tissue, such as muscle, could provide protection for the entire organism. This opens up new possibilities for therapeutic approaches.
Building on previous research, the scientists investigated whether the beneficial effects of cold exposure could be replicated using metabolite supplements. Administering BH2 and tyrosine was sufficient to produce a protective effect both in C. elegans and in cell cultures. This suggests that metabolites may reproduce some of the benefits of cold exposure.
“We were genuinely surprised to discover that supplementation significantly extended lifespan even at standard and warmer temperatures. Further experiments involving human cells encourage us to pursue treatments that mimic the beneficial effects of cold without changing body temperature,” Vilchez said.
The researchers emphasize that it is still too early to talk about developing a “pill” that reproduces the lifespan-extending effects of cold exposure. However, the findings provide a promising starting point for further research into metabolite-based treatments for Huntington’s disease and ALS.