Receptor makes mice strong and slim
Molecule that regulates two side effects of aging identified

Date:
June 25, 2020
Source:
University of Bonn
Summary:
Increasing abdominal girth and shrinking muscles are two common
side effects of aging. Researchers have discovered a receptor
in mice that regulates both effects. Experiments with human cell
cultures suggest that the corresponding signaling pathways might
also exist in humans.



FULL STORY ========================================================================== [Mouse on exercise wheel | Credit: (c) Emilia Stasiak / stock.adobe.com]
Mouse on exercise wheel (stock image).

Credit: (c) Emilia Stasiak / stock.adobe.com [Mouse on exercise wheel |
Credit: (c) Emilia Stasiak / stock.adobe.com] Mouse on exercise wheel
(stock image).

Credit: (c) Emilia Stasiak / stock.adobe.com Close Increasing
abdominal girth and shrinking muscles are two common side effects of
aging. Researchers at the University of Bonn have discovered a receptor
in mice that regulates both effects. Experiments with human cell cultures suggest that the corresponding signaling pathways might also exist in
humans. The study, which also involved researchers from Spain, Finland, Belgium, Denmark and the USA, has now been published in the journal
Cell Metabolism.


==========================================================================
On their surface, cells carry numerous different "antennas," called
receptors, which can receive specific signal molecules. These then
trigger a specific reaction in the cell. One of these antennas is the
A2B receptor. The surfaces of some cells are virtually teeming with it,
for example in the so-called brown adipose tissue. Brown adipose tissue,
unlike its white-colored counterpart, is not used to store fat. Instead,
it burns fat and thereby generates 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. "In the
course of this we discovered an interesting association: The more A2B a
mouse produces, the more heat it generates." Which means the A2B antennas somehow seem to increase the activity of the brown fat cells. But a second observation was even more exciting: Despite their increased fat burning,
the animals weigh hardly less than mice with fewer receptors. "They are slimmer, but at the same time have more muscles," explains Pfeifer.

Muscles like a young mouse In fact, the researchers were able to
show that the muscle cells of mice also carry the A2B receptor. When
this is stimulated by a small molecule agonist, muscle growth in the
rodents is increased. "The receptor regulates both fat burning and
muscle development," emphasizes Pfeifer's colleague Dr. Thorsten Gnad,
the lead author of the study.

As they age, mice increasingly lose muscle mass -- similar to humans. And
just like us, they also tend to gain a lot of fat around the hips over
the years.

However, if they receive the agonist that activates the A2B receptor,
these aging effects are inhibited: Their oxygen consumption (an indicator
of energy dissipation) increases by almost half; moreover, after four
weeks of treatment they have as much muscle mass as a young animal. "A2B activation can therefore reverse both aging effects to a certain extent," explains Gnad.

In order to see whether the results were also meaningful for humans,
the researchers examined human cell cultures and tissue samples. They
found that in people with a large number of A2B receptors, the brown
adipose tissue works at a higher rate. At the same time, their muscle
cells consume more energy, which may indicate that they are also more
active and may be more likely to be regenerated.

"Obesity is a growing problem worldwide," emphasizes Prof. Pfeifer. "Every extra pound not only increases the risk of developing diabetes, but also
the risk of high blood pressure, vascular damage and therefore heart
attacks and strokes. These problems are further exacerbated by muscles
that shrink over the years, as they further reduce the body's energy requirements both at rest and in motion." In addition, poor muscle
strength has an immense impact on the everyday life of older people,
as they are increasingly restricted in their mobility.

The pharmacologists explain that the prospect of having a receptor on
hand that might be able to slow down both of these age-related phenomena
is therefore highly exciting. However, further research would first have
to show to what extent the human mechanisms actually resemble those in
mice. Additionally, there is currently no activator of A2B approved for
use in humans. This means that little is known about any side effects
of such a treatment. "We found no signs of adverse reactions in mice,"
says Pfeifer. "However, the meaningfulness of the results is, of course,
also limited on this matter." Gnad emphasizes that the success of the
study is also the result of good cooperation with numerous international partners: "Nowadays, it is almost impossible to work on complex issues comprehensively without such cooperation."

========================================================================== Story Source: Materials provided by University_of_Bonn. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Thorsten Gnad, Gemma Navarro, Minna Lahesmaa, Laia Reverte-Salisa,
Francesca Copperi, Arnau Cordomi, Jennifer Naumann, Aileen
Hochha"user, Saskia Haufs-Brusberg, Daniela Wenzel, Frank Suhr, Naja
Zenius Jespersen, Camilla Scheele, Volodymyr Tsvilovskyy, Christian
Brinkmann, 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 Blu"her, Rafael Franco, Wilhelm Bloch, Kirsi A. Virtanen,
Alexander Pfeifer. Adenosine/A2B Receptor Signaling Ameliorates
the Effects of Aging and Counteracts Obesity. Cell Metabolism,
2020; DOI: 10.1016/j.cmet.2020.06.006 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200625115916.htm

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