Longevity Briefs: Dehydration – An Overlooked Part Of Growing Old?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Water is pretty important for life. All of the chemical reactions necessary for life take place within water, which dissolves a wider range of substances than any other known solvent. Water is also essential for maintaining the shape of our cells. Even minor dehydration is not without consequence, as blood becomes thicker and the total volume of blood in the body decreases. Severe dehydration causes cells to shrink, impacts nutrient delivery to tissues, and disrupts nerve and muscle function.

Unfortunately, as we age, our ability to maintain optimal levels of hydration is reduced. This is partly because the thirst response to dehydration is weakened, and partly because the kidneys are less able to reabsorb water from the urine, meaning dehydration occurs faster. But why? In this preprint study, researchers attempt to answer that question in detail, at least in mice. This is no easy task, as there are many different systems involved in both sensing and regulating fluid balance.

The discovery:

As expected, elderly mice (26 months old, which is very approximately equivalent to a 70 year-old human) were chronically dehydrated. To figure out why, researchers looked at a hormone called antidiuretic hormone (ADH), also known as vasopressin (AVP), which maintains hydration by increasing water reabsorption in the kidneys. They found that not only were the mices’ kidneys less responsive to AVP, but the AVP-producing neurons in their brains released less of it after the mice had consumed a dry meal when compared to younger mice.

The old mice consumed just as much water over the course of the day as young mice. However, this actually means that they weren’t drinking enough, because they were losing more of that water through their urine than the younger animals. This seemed to be related to a delayed activation of brain cells involved in thirst.

There were also a few surprising findings. While the old mice had a blunted thirst response after consuming dry food, they responded similarly to young mice when researchers manipulated the concentration of their blood directly. When mice were deprived of water for 24 hours, the old mice didn’t actually get any more dehydrated than the younger ones, despite being dehydrated from the start. What’s more, they drank more than the younger ones when given water again. This could be because old mice have worse thirst satiety (in other words, they overdrink). However, the researchers also found evidence that their thirst response was just stronger than that of younger mice. They were more motivated to work for water and had greater dopamine release upon drinking. 

The implications:

The researchers’ goal here was to develop a comprehensive understanding of how the regulation of water within the body is disrupted with age, establishing a baseline for further mouse research. But do their findings carry any relevance for humans? There are similarities between our species: both mice and humans have impaired water reabsorption in the kidneys as they age, as well as a blunted thirst response. However, the mechanisms for this may not be the same. For example, while old mice in this study produced less AVP than their younger counterparts, some evidence suggests that older humans produce more of it, probably to compensate for their impaired kidney function. We’re going to need more human research before we can think about a treatment to fix these problems.

If there’s one takeaway from this research, it’s that older people should probably be making a conscious effort to drink more water throughout the day, as they will be producing more urine and cannot trust their thirst response to tell them when they need to drink more. In fact, there are convincing experiments that even in young people, drinking according to thirst is not enough to maintain the ideal levels of hydration. For a deeper dive into what good hydration is, check out our article on the subject.