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NIH Research Matters

April 28, 2006

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.

image of a nucleus with structural defects

The image above is a nucleus with structural defects, courtesy of Paola Scaffidi, NCI

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.

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Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.

NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

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This page last reviewed on December 3, 2012

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