High-ranking naked mole-rats are more resilient

Date:
April 7, 2022
Source:
Max Delbru"ck Center for Molecular Medicine in the Helmholtz
Association
Summary:
Naked mole-rats are full of surprises. The latest is that
higher-ranked mole-rats most likely have an immunological advantage
over animals with lower social status.



FULL STORY ========================================================================== Naked mole-rats not only look strange, they have a strange lifestyle,
too: they spend their entire lives underground. They also feel very
little pain, rarely develop cancer and are exceptionally long-lived
for a rodent -- living up to 37 years. All this makes the hairless burrow-dwellers prime candidates for scientific study.


==========================================================================
For nearly 20 years, Professor Gary Lewin at the Max Delbru"ck Center
for Molecular Medicine in the Helmholtz Association (MDC) has been
researching these extraordinary animals. "The naked mole rats live in
strictly organized colonies," Lewin says. "Each animal knows its rank
and the tasks it has to perform." Now Lewin's team in the Molecular
Physiology of Somatic Sensation Lab, together with scientists at the
German Cancer Research Center (DKFZ), Freie Universita"t Berlin and the University of Pretoria, has made a new discovery: The researchers report
in Open Biology that naked mole-rats of higher social rank have a larger spleen. The organ plays a key role in the immune system and is involved
in the formation, maturation and retention of immune cells. "This could
mean that higher-ranking animals have better built-in defenses than
animals below them on the social hierarchy," says lead author Dr.

Vale'rie Be'gay of Lewin's team.

No sign of disease, despite an enlarged spleen The shriveled sausages
on four legs are so special that Be'gay carefully examines each naked
mole-rat used in an experiment. She noticed that some of the animals
had a much larger spleen than others. That got her wheels turning.

"We initially thought that the animals with the larger spleens were sick,"
the researcher recounts. That's because the organ swells up when the
body fights inflammation and disease, as many types of immune cells are manufactured and stored there. "But we couldn't find anything, not even inflammatory markers in the blood or any other evidence of disease," she reports. "There had to be another explanation for the enlarged spleen."
With the help of Dr. Alison Barker, Be'gay found out that spleen size
is linked to the animal's social status. The scientist, who recently
studied mole-rat dialects, is very experienced in conducting behavioral research experiments.

They determined rodent rank by having two naked mole-rats run towards
each other in a tube. "The higher-ranked animal will always climb over
the lower- ranked animal," Barker says. "It keeps the upper hand, so to
speak." Higher-ranking animals cope better with disease It was through
this method that the researchers learned that the higher-ranked animals
had enlarged spleens. Be'gay then studied the organs at the molecular
level. She used RNA sequencing and tissue sample analysis to classify
the different immune cells in the spleen. This showed that the number of macrophages is increased in the enlarged organs. Macrophages act as the
body's defense soldiers. They kill invading pathogens by surrounding and swallowing them. That's why they are also called scavenger cells. "The
enlarged spleen might enable the higher-ranked animals to fight
infections better and deal with inflammation and injury more easily,"
Be'gay explains.

A stronger immune system in higher-ranking animals is not unique to
naked mole- rats. In macaques, too, the higher-ranked group members are
better equipped to fight disease. But instead of an enlarged spleen,
the monkeys have a differently organized system of immune protection. "It really surprised us that there could be such large differences in spleen
size without disease being present," Lewin says. "The rank of a naked
mole-rat depends on how it behaves in the group. The size of the spleen
is linked in turn to rank. This would ultimately mean that behavior
directly affects the physical characteristics of the immune system,
or vice versa." The queen never experiences menopause The researchers
also suspect that the spleen influences an animal's longevity.

Successful naked mole-rats -- that is, those able to get their way
with other colony members -- live longer. The queen does not typically
die of old age, but is usually killed during a "coup" -- namely, when
another female gathers male followers around her and removes the old
queen. "Up until her last day, the queen is fertile," says Lewin. "She
never experiences menopause -- as if her organism did not age." This
suggests at the very least that a strong immune system slows down the
aging process. Mammals do not usually produce offspring until the end
of their lives: they have a post-reproductive lifespan.

The scientists are now asking new questions. For instance, which comes
first: the larger spleen or the higher rank? This has not yet been
determined. The only thing that is clear is that naked mole-rats are
not born into their social status, but work their way up. The desire
for sex may be their driving force: Only the highest-ranking members --
the queen and two to three pashas -- are allowed to reproduce. "This
could be a selection mechanism," Lewin says. "By allowing only the most successful to mate, it ensures that the animals with the strongest immune systems pass on their genes." Lewin also hopes to gain new insights
into cancer. Naked mole-rats have a very efficient defense system
against the disease. Whether the spleen plays a role in this remains to
be seen. First, the scientists must conduct further cell analysis. "We
are still at the very beginning," he stresses.


========================================================================== Story Source: Materials provided by Max_Delbru"ck_Center_for_Molecular_Medicine_in_the
Helmholtz_Association. Original written by Jana Ehrhardt-Joswig. Note:
Content may be edited for style and length.


========================================================================== Related Multimedia:
* High-ranking_naked_mole-rats ========================================================================== Journal Reference:
1. Vale'rie Be'gay, Branko Cirovic, Alison J. Barker, Robert
Klopfleisch,
Daniel W. Hart, Nigel C. Bennett, Gary R. Lewin. Immune competence
and spleen size scale with colony status in the naked mole-rat. Open
Biology, 2022; 12 (4) DOI: 10.1098/rsob.210292 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220407141919.htm

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