An international team of researchers led by molecular biologist David Vilches at the University of Cologne in Germany has discovered a previously unknown molecular pathway through which cold temperatures extend the lifespan of organisms. The findings were published in the prestigious journal Nature, according to infohub.kz.
The biologists found that moderate cold triggers the production of a metabolite called BH2 in muscles, which protects cells from toxic proteins and extends lifespan even under normal warm conditions, ScienceAlert reports.
It turned out that longevity under cool conditions is not a passive consequence of a slowed metabolism but an active physiological process.
In experiments on the roundworm Caenorhabditis elegans, the scientists established that exposure to moderate cold (15 degrees Celsius) sharply stimulates the production of the enzyme CAT-4 in muscle tissue. This enzyme triggers the synthesis of a special metabolite, dihydrobiopterin (BH2). Muscles accumulate it and then release it into other tissues of the body. There, BH2 is transformed into tetrahydrobiopterin (BH4), enabling the enzyme PAH-1 to produce the amino acid tyrosine, which maintains protein balance.
The researchers found that activation of this pathway suppresses the dangerous accumulation of toxic protein aggregates in Huntington's disease. The main discovery was that cold itself is not required to trigger this protective effect. By genetically increasing CAT-4 levels in the worms' muscles, the scientists achieved an extension of their lifespan even at normal and elevated temperatures.
Experiments on human cells confirmed the therapeutic potential of the mechanism. Adding the metabolite BH2 reduced the accumulation of pathological proteins in cell cultures carrying markers of amyotrophic lateral sclerosis (ALS) and Huntington's disease, and also protected human motor neurons from death. In the future, this could make it possible to create drugs that mimic the benefits of cold for humans.