An orchestra in a concert hall: the conductor raises the baton, and the musicians come in. That's how the thirst system works in young mice: the brain gets a signal about food, and drinking starts almost immediately, like a well-rehearsed chord. But with age, the conductor's baton begins to slow down, while the musicians, on the contrary, play louder when they're given a solo. By 26-30 months, which corresponds to 73-81 years in humans, a mouse's body can no longer respond to thirst in time, even though the need for water itself doesn't go away.
To see this breakdown, scientists compared mice of different ages across many parameters: from blood composition to the activity of individual neurons. It turned out that old animals have more concentrated blood plasma: 330 versus 312 mOsm/kg in young males. This means there are more dissolved substances and less water in the blood, that is, chronic dehydration. At the same time, their urine is more diluted and its volume is larger, and the hormone vasopressin, which makes the kidneys retain water, is produced less: 409 versus 665 pg/ml in urine. The kidneys also respond less well to this hormone, so water leaves the body too easily.
But the most interesting thing happens after a meal. In young mice, drinking begins just 4 minutes after eating, while in old males it starts after 21.3 minutes. The brain neurons that release vasopressin activate more slowly: 18.3 minutes versus 13.7. The link between eating and drinking breaks, as if the conductor has lost the score. And if old mice are deprived of water for a day, they drink more than young ones: 795 versus 489 licks in males, press the lever harder for water, and experience pleasure from drinking longer, judging by dopamine release (74.8 versus 38.1 seconds).
This paradox is explained by the fact that the thirst system ages unevenly. Some pathways, coming from the mouth and intestines, degrade, so the mouse doesn't notice it's time to drink after a meal. Other pathways, which sense dehydration through the blood, remain intact or even strengthen. That's why after severe thirst, old mice drink with double energy. Previously it was unknown which specific nodes of this system break and which remain intact. Now it's clear: chronic dehydration arises from a deficiency of and insensitivity to vasopressin, not from a decline in thirst as such.
For doctors, this means that elderly patients need more than just reminders to "drink more"; they need an understanding that their body senses its internal signals differently. Perhaps water should be offered more often right after meals, when the link between eating and drinking is weakened. The orchestra is aging, but the music can still be tuned if you know which string is out of tune.
Old mice often drop and scatter their food, so to eat the same amount they need to fuss with the pellets longer. This does not prevent them from eating normally, but it delays the start of drinking after a meal.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.