Progeria Gene Implicated in Normal Aging
Recent research has revealed that Hutchinson-Gilford Progeria Syndrome (HGPS),
a disease of premature aging, is caused by mutations in a gene called LMNA.
Now, scientists at NIH's National Cancer Institute (NCI) have shown that the
same gene plays a role in normal aging as well.
In people with HGPS, there are various flaws within the cell's nucleus, the
compartment that contains the genetic information. These flaws include more unrepaired
DNA damage, lower levels of certain nuclear proteins and altered chemical modification
patterns. The new findings, published online by Science on April 27,
show that cells of healthy older people display the same defects.
The genetic mutation that leads to HGPS results in the production of a shortened
form of lamin-A, the protein encoded by LMNA. The NCI researchers found
that small amounts of this abnormal lamin-A protein are also made in healthy
people. When the researchers prevented cells from healthy older donors from producing
this faulty lamin-A protein, the nuclear defects were reversed. This suggests
that the abnormal lamin-A causes the age-related nuclear defects.
The researchers conclude that the same molecular mechanism responsible for the
very rare HGPS disease acts at a low level in healthy cells. The accelerated
aging of HGPS patients may therefore reflect an exaggerated version of the normal
aging process. These results suggest that HGPS can now be used as a model system
to study normal aging. Whether manipulating lamin-A might influence the overall
aging of an individual is unknown right now, but it's an intriguing idea.
The image above is a nucleus with structural defects,
courtesy of Paola Scaffidi, NCI
|
