Moderately cold temperatures have proven to effectively extend lifespan and delay age-related decline in animals. However, how cold temperatures trigger these beneficial effects at the molecular level has remained largely unclear. In their study, the research team led by Professor Dr David Vilchez at the CECAD Cologne Cluster of Excellence on Aging and Aging-associated Diseases, the Centre for Molecular Medicine Cologne (CMMC) at the University of Cologne, and University Hospital Cologne was able to decipher a signalling system that is regulated across different tissues by metabolites. Using Caenorhabditis elegans as a model organism, they demonstrated a link between cold temperatures, increased lifespan and proteostasis – the maintenance of protein homeostasis. They found that muscle acts as a ‘central factory’, producing the metabolite dihydrobiopterin (BH2). BH2 is then transported to other tissues, where it is used to induce the production of the amino acid tyrosine. This metabolic pathway helps strengthen the cellular machinery responsible for maintaining functional proteins and preserving protein homeostasis. The study ‘Cold activates a BH2 metabolic network promoting longevity and proteostasis’ has been published in the journal Nature .
As part of their study, the scientists used the nematode C. elegans as a model organism and further validated their findings in human cell models of Huntington’s disease and amyotrophic lateral sclerosis (ALS). Both are age-associated neurodegenerative diseases in which the accumulation of misfolded or damaged proteins is a major feature.
“We are excited to show that mildly cold temperatures trigger significant production of a specific metabolite, BH2, which is synthesized, stored, and subsequently released by muscle tissue. BH2 then goes to other parts of the body, where it helps to maintain protein homeostasis and contributes to tissue health during aging,” explains principal investigator David Vilchez. “These findings suggest that specifically targeting a single tissue, such as muscle, could provide organism-wide protection. This opens up new avenues for therapeutic approaches.”
Building on previous studies of cold temperatures, the researchers also asked whether the beneficial effects of cold temperatures could be reproduced by supplementing the metabolites identified in their study. Remarkably, administration of both BH2 and tyrosine was sufficient to produce a protective effect in C. elegans as well as the cell cultures, suggesting that these metabolites can reproduce some of the beneficial effects of cold.
“We were genuinely surprised to find the supplementation significantly extended lifespan, even at standard and warmer temperatures. Further experiments on human cells encourage us to look for treatments that mimic the beneficial effects of cold without requiring changes in body temperature.”
It is still far too early though, at the current state of research, to develop a ‘pill’ that replicates the longevity-promoting effects of cold temperatures. However, the results of the study do provide a good starting point for further research into metabolite-based treatment options for conditions such as Huntington’s disease and ALS. The project was carried out in collaboration with the laboratories of Professor Dr Thorsten Hoppe and Professor Dr Christian Frezza at the CECAD Cluster of Excellence.
Nature
Experimental study
Animals
Cold activates a BH2 metabolic network promoting longevity and proteostasis
21-Oct-2026