Scientists have long seen that animals often live longer when kept moderately cold, but how that works has been unclear. A study published in the journal Nature on 21 October 2026 offers one answer, at least in a tiny lab worm: cold makes the worm’s muscles produce a molecule called dihydrobiopterin, or BH2, which travels to other parts of the body, helps keep proteins from clumping and lengthens life1.
The work was done mainly in Caenorhabditis elegans, a worm about a millimeter long that labs use to study basic biology2. The team also ran tests in human cells grown in a dish1. No people or mammals were treated.
What the researchers report
The paper’s authors start from a known pattern: moderately cold temperatures extend lifespan and support health across many species, yet the molecular reasons have stayed unclear1. They describe what they call a “metabolite-driven, multi-tissue signalling system”, meaning a chain of small chemical messengers that links several organs, which connects cold to longer life and better protein upkeep in the worms1.
Protein upkeep, which scientists call proteostasis, is the body’s work of keeping proteins correctly folded and clearing out damaged ones. When it fails, proteins can stick together into clumps, a feature of several brain diseases1.
How the cold signal works, step by step
The study lays out a sequence of steps, all reported in worms1:
- Cold switches on an enzyme. Cold temperature raised the level of an enzyme called CAT-4, which helps make a family of molecules called biopterins. In humans the matching enzyme is called GCH11.
- Muscle makes BH2. More CAT-4 meant more BH2. The authors describe BH2 as a transportable reserve of a more active helper molecule, tetrahydrobiopterin, or BH41.
- BH2 travels. BH2 is made in muscle and carried to distant tissues, including the gut and nerve cells1.
- It is switched on where it lands. In those tissues, an enzyme called DHFR-1 turns BH2 into BH41.
- BH4 helps make tyrosine. BH4 is a required helper for an enzyme called PAH-1, which drives the making of a molecule called tyrosine. This step was linked to longer life1.
One result stands out because it separates the effect from the cold itself. The authors report that boosting BH2 production only in muscle was enough to lengthen the worms’ lives and to reduce harmful protein clumps in other tissues, even when the worms were kept at normal or higher temperatures1.
Protein clumps in worms and in human cells
Beyond lifespan, the researchers say this BH2-to-BH4 pathway prevented disease-related protein clumping in the worms, and the loss of nerve function that follows it, as the animals aged1.
They then moved to human cells in a dish. Adding either BH2 or tyrosine reduced clumping of three kinds of problem proteins1:
- stretched-out versions of proteins (so-called polyQ proteins) linked to Huntington’s disease, an inherited brain disorder;
- faulty versions of a protein called TDP-43 that cause amyotrophic lateral sclerosis (ALS), a disease that destroys the nerves controlling movement;
- faulty versions of another protein, FUS, that also cause ALS.
These dish results show an effect on clumping inside cells. They do not show that adding these molecules changes the course of Huntington’s disease or ALS in a person.
What it does not show yet
The lifespan findings come from worms, and the human data come from cells in a dish1. That leaves several open questions:
- Mammals. The summary of the paper reports no tests in mice or other mammals1. Mammals handle cold very differently from worms. In mice, for example, cold triggers extra heat production through shivering and through brown fat, and adult humans have little brown fat compared with mice, according to a 2021 talk by metabolism researcher Alexander Bartelt3.
- Size of the effect. The study summary does not give how much longer the worms lived, so Biohack cannot report a figure.
- Safety and dosing. Nothing in the paper’s summary addresses giving BH2 or tyrosine to people.
Worm results have a mixed record of carrying over to more complex animals. In 2014, when another lab reported that a metabolite called alpha-ketoglutarate made worms live about 50% longer, aging researcher Matt Kaeberlein, who was not involved, told Nature it was too early to call it an anti-aging drug4. At the time, Brian Kennedy, then president of the Buck Institute for Research on Aging, said longer-term studies in animals closer to humans were needed, adding:
We don’t just want to make the animals live longer. We want to make them healthy longer.4
Earlier still, a 2000 study reported that synthetic antioxidant drugs extended worm lifespan by about 50%5. Such worm findings are useful for finding mechanisms, but each still needs testing in other species.
Who is behind it
The paper lists 17 authors, beginning with H. J. Lee and ending with D. Vilchez, and including T. Hoppe and C. Frezza1. The abstract Biohack reviewed does not name the authors’ institutions or the study’s funders, and it does not mention any company ties. Biohack will add those details if they become available from the full paper or the institutions involved.
No product is attached to the findings in the material reviewed, and the authors do not describe a drug candidate.
How it fits the field
The idea that cold and long life are connected is not new. Researchers have long known that many animals live longer in colder climates, and earlier worm work had already tied that pattern to particular proteins6. Worms also turned out to be useful for finding how animals sense cold: a lab at the University of Michigan found a cold-sensing protein in C. elegans in 2019 and later confirmed a related cold sensor, GluK2, in mice2.
What this Nature study adds is a proposed route from cold to longer life that runs through muscle and a molecule that can travel between organs1. It also connects cold to protein upkeep. Protein quality control has come up in cold research in mammals too: in mice, brown fat raises its protein-clearing activity during long cold exposure, driven by a factor called Nfe2l1, according to Bartelt’s group3. Those are different molecules in a different animal, so the two lines of work should not be treated as the same finding.
The study also fits a wider theme in aging research of organs signaling to one another. Biohack recently covered another lab study in which putting force on old mice’s leg bones was linked to longer life, and one in which an “energy saver” drug lengthened life in yeast, worms and flies.
What to watch next
The authors conclude that BH2 is a cold-induced molecule whose production, transport between tissues and conversion into active BH4 help preserve protein upkeep across the body and extend lifespan in worms1. The next questions are whether the same chain, which in humans would involve the enzyme GCH1, behaves similarly in mammals; whether raising BH2 in mouse muscle has any effect on aging or protein clumping; and whether the dish results in Huntington’s and ALS cell models hold up in animal models of those diseases1.
Until then, the finding is a detailed map of one mechanism in a worm, with early supporting signs in human cells. It is not evidence that cold exposure, BH2 or tyrosine lengthens human life.
