Slim and strong: Molecular adjustment screw discovered

Reduce the side effects of aging Slim and strong: Molecular adjustment screw discovered

There is no denying it: with age, our abdominal girth usually increases and muscle strength wanes. Researchers at the University of Bonn have now discovered a receptor in mice that regulates both obesity and muscle shrinkage as side effects of aging. Corresponding signaling pathways could also exist in humans – this harbors potential for the (therapeutic) slowing down of these signs of aging.

Bonn – Cells have numerous different “antennas” on their surface, called receptors, which can receive specific signaling molecules. They then trigger a very specific reaction in the cell. One of these antennas is the A2B receptor. The surface of some cells is teeming with him – for example in the so-called brown adipose tissue. Unlike its white-colored relative, brown adipose tissue is not there to store fat. Instead, it burns fat and creates heat.

“In our publication, we took a closer look at the A2B receptors in brown adipose tissue,” explains Prof. Dr. Alexander Pfeifer from the Institute of Pharmacology and Toxicology at the University Hospital Bonn. “We came across an interesting connection: The more A2B a mouse forms, the more heat it produces.”

The A2B antennas seem to somehow increase the activity of the brown fat cells. But a second observation was even more exciting: Despite their increased fat burning, the animals hardly weigh less than their peers. “Although they are leaner, they have more muscles at the same time,” explains Pfeifer.

Muscles like a young mouse

In fact, in their study, which also included scientists from Spain, Finland, Belgium, Denmark and the USA, the researchers were able to demonstrate that the muscle cells of mice also carry the A2B receptor. If it is stimulated by the right molecule, this stimulates muscle growth in the rodents. “So the receptor regulates both – fat burning and muscle building”, emphasizes Pfeifer’s employee Dr. Thorsten Gnad, the first author of the study.

Mice break down muscles more in old age – similar to humans. Like us, they also tend to gain a lot of fat over the years around their hips. However, if they receive an active ingredient that activates the A2B receptor, it inhibits these aging effects: their oxygen consumption (an indicator of fat burning) increases by almost half; after four weeks of treatment, they also have as much muscle mass as a young animal. “The A2B activation can therefore reverse both aging effects to a certain extent,” explains Gnad.

Humans also have a large amount of A2B receptors

In order to see whether the results are meaningful to humans, the scientists also examined human cell cultures and removed tissue. They found that in people with a large amount of A2B receptors, the brown adipose tissue runs faster. At the same time, their muscle cells consume more energy – a possible indication that they are also more active and may be newly formed.

“Overweight is an increasing problem worldwide,” emphasizes Prof. Pfeifer. “Every kilo more increases not only the risk of developing diabetes but also the risk of high blood pressure, vascular damage and thus also of heart attack and stroke. The muscles that shrink over the years exacerbate these problems, since they further reduce the body’s energy requirements both at rest and when moving.

Slow down signs of aging (therapeutically)?

The prospect of having a receptor on hand that could possibly slow down both signs of aging is therefore electrifying, the pharmacologists explain. First of all, however, further research would have to show to what extent the mechanisms in humans actually resemble those in the mouse. At the moment there is also no approved active ingredient that can stimulate the A2B receptor. Accordingly, little is known about any side effects of such treatment. “We did not find any signs of intolerance in mice,” says Pfeifer. “However, the informative value of the results is of course also limited on this question.”

The success of the study is also due to the good cooperation with the numerous international partners, Gnad emphasizes: “Without such cooperation, complex questions can hardly be dealt with comprehensively today.”

Originalpublikation: Thorsten Gnad, Gemma Navarro, Minna Lahesmaa, Laia Reverte-Salisa, Francesca Copperi, Arnau Cordomi, Jennifer Naumann, Aileen Hochhäuser, Saskia Haufs-Brusberg, Daniela Wenzel, Frank Suhr, Naja Zenius Jespersen, Camilla Scheele, Volodymyr Tsvilovskyy, Joern Rittweger, Christian Dani, Mathias Kranz, Winnie Deuther-Conrad, Holger K. Eltzschig, Tarja Niemi, Markku Taittonen, Peter Brust, Pirjo Nuutila, Leonardo Pardo, Bernd K. Fleischmann, Matthias Blüher, Rafael Franco, Wilhelm Bloch, Kirsi A Virtanen, Alexander Pfeifer: Adenosine / A2B receptor signaling ameliorates the effects of aging and counteracts obesity. Cell Metabolism, DOI: https://doi.org/10.1016/j.cmet.2020.06.006.

* J. Seiler: Rheinische Friedrich-Wilhelms-Universität Bonn, 53115 Bonn

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