How Fasting Fish Can Help Scientists Extend Us | Hello

Fasting: People have been doing it for centuries. But there are many things we still don’t know about its advantages and disadvantages. In a new episode of the DW Science Unscripted podcast, Connor Dillon and Gabriel Borud discussed a study from the Max Planck Institute for Aging in Cologne, Germany, that investigated what happens when fish rush. Connor and Gabe spoke with the director of the institute, Adam Antebi. This interview is excerpted from our Science Unscripted podcast. If you’re interested in the full interview (and want to see how fasting can affect our lifespan too), you can watch this episode of Science Unscripted on YouTube. Or you can subscribe to the audio podcast.

DU: Before we talk about what happened to the fish, we need to make one thing clear. Does fasting work? What does it actually do? What does the research say about this?

Starvation is more beneficial for younger marine fish, researchers have found. (HPIC/dpa/picture-alliance)

Adam Anteby: Many people engage in intermittent fasting or calorie restriction because it has health benefits. It appears to lower blood sugar and cholesterol and reduce, in some cases, age-related diseases. I think it has clear health benefits for many people and model organisms. But the question is, is it true for all ages and for all people?

What did you do in your experiment? You worked with fish.

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It actually started before us. That’s other people’s business. If you look at mice and try to restrict their diet at an older age, they don’t respond well either. They don’t get the benefits. And it is not clear why. It’s also true even in humans that if you cut back on protein at an early age, you get health benefits. But later in life, these health benefits seem to fade to some extent. So we use the killifish as our model system because that fish only lives for about six to eight months, and we can see in real time the impact of starvation in young and old animals and the effect it has on the lifespan of the animal.

So, basically, if I fast early in life, it will affect me, usually in a positive way. And later in life either not at all or not so much. And with fish you can do this for eight months. “Later life” with the fish will be their sixth month or something?

More like four and a half, five months we start these experiments. You know, many people want to lose weight. Fasting or cutting calories or intermittent fasting is a good way to lose weight. So, that’s beneficial. But if your goal is to keep your muscles, this is where the questions really start to arise. And in a young person, they can probably keep their muscle mass. In older people, this becomes a problem because one of the things about aging is that you tend to lose muscle sarcopenia. And so fasting can have a detrimental effect. So we really wanted to study this in a rigorous way in these fish.

What happened to the fasting murders?

It was quite a surprise. We expected that young fish would perform better than old fish. But what we saw was that when we starved young fish, there were changes in the genes that went up and down. When we looked at older animals, the number of genes going up and down was much smaller. And at first we thought, well, maybe they’re just not responding to the fasting part. But what we found is that they don’t respond to the feeding part and seem to be stuck in this constant starvation trap even though they are ingesting food. They are indeed anabolically resistant in many ways.

What is the difference between these two phases when I am fasting and when I am eating?

When you fast, you decrease protein synthesis. Normally, you build proteins for all kinds of activities in your body. But when you fast, you reduce that because you don’t have as many resources to build on. You also suppress energy metabolism and also start breaking down fat and glucose for the energy you need. When you’re fed, a lot of that reverses. You turn on protein synthesis, you turn on fat production. Basically, you’re setting yourself up for growth.

What’s also very interesting is that when you fast these old fish, they show signs of increased inflammation above and beyond what you normally have with aging. And that sounds to us like it’s a detrimental effect to starve old fish because you increase the amount of inflammation. And that can be detrimental to many of the fabrics you’re looking at.

What was the point of the experiment? Just to find this in the fish or what?

What we really want to understand is why this happens and what the mechanism is. And one of the things that we found from our data, looking at what genes go up and down, was that there’s this energy sensor called AMP activated kinase. It detects low energy and tries to increase energy production to keep things in balance. What we noticed is that this enzyme, this energy sensor, is made of three subunits. One of these is called the gamma subunit. And what we saw was quite astounding. Gamma one subunit was elevated in the fed state. In young animals, the gamma two subunit is elevated in the fasted state. They were in this feedback loop. And with aging, gamma two is always up, gamma one never turns on. We believe that this cycle of fasting and eating is very important for health. You should increase gamma two during fasting and increase gamma one during feeding phase.

Is it possible to take these two sliders, gamma one and gamma two, and slide them into the older fish to make them young again?

yes That’s why we use these model genetic organisms. Because we can genetically manipulate them very easily. Our idea was, if gamma is low in an adult fish, why not activate it genetically and see what happens to the starvation response and what happens to metabolic health.

What happened?

Remarkably, what you see is a young animal having a normal response to fasting. And in an old animal, they also had a youthful repeated fasting response. And it looks perfect. They have much lower levels of inflammation. They do not break down fats, but synthesize them. And above all, their energy metabolism seems to be increased.

Did they live longer?

yes This is the most amazing thing. This one amino acid change made these fish live about 10% to 20% longer. And not only do they live longer, but if you look at the different tissues of this fish, they look much younger. For example, if you look at fin regeneration, there is much more regeneration in these older animals. We think this is a really great result. And now we have this long-lived, healthier fish that we can study in detail and give it more mechanisms.

What about us? For people? Can you tell that an amino acid can change our lives?

Well, not genetically, but maybe pharmacologically. That would be one of the goals. But let me answer your question another way. Do we see the same dynamic in humans? And I’d say we haven’t quite nailed it. But from what we can see in the data we’ve looked at, gamma-ta in humans, like bloodfish, declines with age.

We did a very nice collaborative study with some of the geriatricians here at the University of Cologne in the clinics. They look at people and their frailty and ability to function in old age. We found that if you look at the expression level of gamma one in these people, in the leanest individuals, gamma one is the lowest. When gamma 1 is low, they are the most fragile. And when gamma one is higher, they are the healthiest.

We think it could be a biomarker for health and longevity in humans. That needs to be determined. And right now we don’t know if there is a causal effect. And there are many questions yet to be answered. But there may be a human connection.

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