The University of Edinburgh team rebuilt the thymus — an organ central to the immune system and found in front of the
heart — of very old mice by reactivating a natural mechanism that
gets shut down with age.
The regenerated thymus was not only similar in structure and genetic
detail to one in a young mouse, the scientists said, but was also
able to function again, with the treated mice beginning to make more
T-cells — a type of white blood cell key to fighting infections.
The regenerated thymus was also more than twice the size of the aged
organs in the untreated mice.
"By targeting a single protein, we have been able to almost
completely reverse age-related shrinking of the thymus," said Clare
Blackburn from Edinburgh's Medical Research Council (MRC) Centre for
Regenerative Medicine, who led the research.
"Our results suggest that targeting the same pathway in humans may
improve thymus function and therefore boost immunity in elderly
patients, or those with a suppressed immune system."
She added however, that while the treated mice were making T-cells,
her research could not yet establish whether the immune systems of
the older mice were strengthened.
And before the technique can be tested in humans, she said,
researchers will need to conduct more animal experiments to make
sure the regeneration process can be tightly controlled.
The thymus is the first organ to deteriorate as people age. This
shrinking is one of the main reasons the immune system becomes less
effective and we lose the ability to fight off new infections, such
as flu, as we get older. Regenerative medicine is a
fast-growing area of research, mainly focused on stem cells — the
master cells that act as a source for all types of cells and tissues
in the body. One of the central aims is to harness the body's own
repair mechanisms and manipulate them in a controlled way to treat
disease.
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Blackburn's team, whose work was published on Tuesday in the
journal Development, said they targeted a part of the process by
which the thymus degenerates — a protein called FOXN1 that helps
control how key genes in the thymus are switched on.
They used genetically modified mice to enable them to increase
levels of this protein using chemical signals. By doing so, they
managed to instruct immature cells in the thymus — similar to stem
cells — to rebuild the organ in the older mice.
Rob Buckle, the MRC's head of regenerative medicine, said this
success with the mouse thymus suggests organ regeneration in mammals
can be directed by manipulating a single protein — something he said
could have broad implications for other areas of regenerative
biology.
(Editing by Pravin Char)
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