How Cold Temperatures Help Worms Live Longer, and Why Muscle Is the Key

Scientists have long known that cooler temperatures extend life in many animals. A new study in the journal Nature suggests part of the reason is an active chemical signal that starts in muscle, according to ScienceAlert. The work was done in tiny worms and in human cells in the lab, not in people.

The research team, which includes molecular biologist David Vilchez of the University of Cologne in Germany, identified a metabolic substance called dihydrobiopterin, or BH2, that appears to carry the benefit of cold from muscle to the rest of the body.

What did the researchers find?

In experiments with the roundworm Caenorhabditis elegans, mildly cold conditions of 15 degrees Celsius (59 degrees Fahrenheit) raised production of an enzyme called CAT-4, mostly in the worms' muscles. That enzyme in turn drives production of BH2, which muscle tissue makes, stores and later releases, ScienceAlert reported.

Once BH2 reaches other tissues, it is converted into a molecule called tetrahydrobiopterin, or BH4. That molecule lets another enzyme, PAH-1, make the amino acid tyrosine.

Is the effect just a side effect of a slower metabolism?

The study points away from that idea. When the team disrupted this pathway, worms in the cold lost part of their longer lifespan. That suggests the longevity effect of cold is not only a passive result of slower body chemistry but is partly an actively regulated process that begins in muscle cells.

Researchers had long wondered how cold worked. Early explanations focused on simple thermodynamics, but more recent work has pointed to specific biological pathways that help organisms survive.

Does it work without the cold?

In worms, it seems to. By genetically raising CAT-4 levels in the worms' muscles, the team extended their lifespan even at normal or warmer temperatures. Vilchez said the researchers were “genuinely surprised” by how much supplementation extended life at those temperatures.

The finding suggests some benefits of cold might be reproduced without lowering body temperature, though only in these experiments so far.

What did the experiments show about protein damage and disease?

The pathway also supported healthy protein balance, known as proteostasis. In a worm model of Huntington's disease, it suppressed the clumping of harmful proteins.

In human cells engineered to produce proteins linked to Huntington's disease and amyotrophic lateral sclerosis, or ALS, adding BH2 reduced the buildup of the abnormal proteins. In another experiment, BH2 and tyrosine reduced signs of programmed cell death in human motor neurons that carried an ALS-linked mutation. That hints the pathway could help guard against nerve cell damage.

The same team had reported a few years earlier that cold helps clear harmful protein clumps in the worms by activating cell structures called proteasomes, which break down protein waste.

Why does it matter?

If the same chain of events works in people, treatments could one day mimic the benefits of cold without anyone having to change their body temperature. Vilchez said the results suggest that targeting a single tissue, such as muscle, could protect the whole organism, and that this opens new avenues for therapies.

That is a long way from a treatment, however. So far the results come only from worms and human cells grown in the lab. ScienceAlert stressed that much more research is needed before anyone can consider whether these effects could be transferred safely to living human patients.

For now, the study offers a clearer picture of how cold may support a longer, healthier life in animals, and a specific molecule that scientists can follow up on.

Around Prague, based on reporting by ScienceAlert