Five different roads lead to a single destination: a long life. Some mice received drugs, others ate 40% less than usual. After eight months, seven tissues were collected from all of them: brain, liver, muscle, kidney, fat, blood. Each tissue is a separate witness, seeing what happens from its own angle.
To hear all the witnesses at once, the scientists used machine learning. The algorithm sifted through the data a thousand times to distinguish the intervention mice from ordinary ones. It's like questioning each witness many times over so that a random slip of the tongue doesn't throw you off. It turned out that in all tissues, the long-lived mice differ from the controls.
Among thousands of molecules, only two recurred in several tissues. Ergothioneine, a substance from mushrooms that mice get from food, accumulated in the brain and blood under all five lifespan-extending methods. In muscle, cardiolipin 72:8 rose, a fat of the inner membrane of mitochondria, the cell's power plants. These molecules are like shared words in the testimony of different witnesses.
Previously it was unclear whether different lifespan-extending methods share a common molecular signature. Now it's clear: they do. Ergothioneine and cardiolipin change in the same way, even though most other changes depend on the tissue. This discovery could speed up the search for anti-aging drugs: it's enough to measure these molecules in the blood after a short course of a drug and compare them with the profile of long-lived mice.
Five roads, seven witnesses, two shared words. The signature of longevity has been left behind, and now it can be sought in humans.
Ergothioneine is an antioxidant that mammals cannot synthesize themselves. It is produced by fungi, and mice obtain it from food via a special transporter, OCTN1.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.