Cold Triggers a Hidden Molecular Pathway That Extends Lifespan

Researchers have identified a molecular pathway that helps explain why moderate cold can extend lifespan in animals. In experiments with the nematode worm C. elegans, exposure to 15 °C increased production of the enzyme CAT-4, mainly in muscle. CAT-4 stimulated production of the metabolite BH2, which traveled to other tissues and was converted into BH4. This enabled the enzyme PAH-1 to produce tyrosine. Disrupting the pathway weakened cold’s lifespan benefits, supporting the idea that cold activates biological signals rather than extending life simply by slowing metabolism. The pathway also improved protein homeostasis, reducing harmful protein clumps in a worm model of Huntington’s disease.

The researchers found that boosting CAT-4 in worms could extend lifespan even at normal or warmer temperatures, suggesting some benefits of cold might be reproduced without lowering body temperature. In experiments with human cells, BH2 reduced abnormal protein accumulation associated with Huntington’s disease and ALS; BH2 and tyrosine also reduced signs of cell death in motor neurons carrying an ALS-related mutation. These results point to muscle as a possible source of signals that protect tissues throughout the body, and raise the prospect of treatments that mimic cold’s effects. However, the findings come from worms and cultured human cells, not living people. Much more research is needed to establish whether the pathway can be safely targeted in humans.