Germany describes pathway through which cold extends worms’ lifespan — ScienceAlert
Molecular biologist David Vilchez of the University of Cologne in Germany and his colleagues described a mechanism that, according to the study, contributes to extending the lifespan of the nematode Caenorhabditis elegans under moderate cold conditions. As ScienceAlert reports, the metabolite dihydrobiopterin, or BH2, plays a key role in this process. The study’s results were published in the journal Nature.
A signal from muscle tissue
In the experiments, the nematodes were kept at a temperature of 15 °C — under such conditions, their lifespan increases. Cold enhanced the production of the CAT-4 enzyme, predominantly in the worms’ muscles. This, in turn, stimulated the formation of BH2, which was synthesized, accumulated, and released by muscle tissue.
BH2 was then transported to other tissues, where it was converted into tetrahydrobiopterin, or BH4. This bioactive molecule enabled the PAH-1 enzyme to synthesize the amino acid tyrosine. When scientists disrupted this pathway, the lifespan benefits of cold for the worms decreased. This indicates that the effect of lower temperature is not limited solely to slowing metabolism, but is partly linked to an active biological response.
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Experiments on cellular models
The researchers also found that this pathway supports proteostasis — the ability of cells to maintain proteins in their normal state. In a nematode model of Huntington’s disease, it suppressed the aggregation of harmful proteins.
Genetically increasing CAT-4 levels in the worms’ muscles extended their lifespan even at normal or higher temperatures. In separate experiments on human cells, adding BH2 reduced the accumulation of abnormal proteins associated with Huntington’s disease and amyotrophic lateral sclerosis. Adding BH2 and tyrosine also reduced signs of programmed death in motor neurons with a mutation associated with amyotrophic lateral sclerosis.
The authors emphasize that the results have so far been obtained only in experiments on nematodes and human cells. Further research is needed for the potential safe application of these findings in humans.
