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Cellular Defects in Premature Aging Disease are Reversible

Cells affected by Hutchinson-Gilford Progeria Syndrome (HGPS) -- a disease associated with premature aging -- can be made healthy again, according to findings by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). Using specially modified segments of DNA, NCI researchers Paola Scaffidi, PhD, and Tom Misteli, PhD, reversed the abnormalities seen in HGPS cells by correcting defects associated with the key protein, lamin A. By demonstrating that HGPS cellular characteristics are reversible, this study, appearing in Nature Medicine online on March 6, 2005, brings scientists one step closer to understanding this devastating childhood disease and might provide insights into the normal aging process.

HGPS is a rare inherited disease affecting about one in eight million children. While appearing normal at birth, infants with HGPS age rapidly after their first 18 months, and physical symptoms include stunted growth, loss of hair and body fat, joint stiffness, osteoporosis, and heart problems. The condition is fatal, with heart disease being the leading killer, and affected children usually die before they reach their late teens.

Less than two years ago, NIH-led researchers discovered that the genetic basis for HGPS is a single mutation in the gene encoding lamin A. Lamin A is a critical structural protein that acts as the scaffolding which holds a cell's nucleus together. Lamin A is defective in HGPS cells because the mutation creates an aberrant splice site in the lamin A gene; the aberrant splicing, or joining the separate parts of the gene together, results in synthesis of a truncated lamin protein. Without lamin A holding them together, the nuclei of progeria cells become wrinkled and misshapen. In addition, numerous other nuclear proteins show reduced expression.

"Our NCI team at the Center for Cancer Research in Bethesda set out to ask whether these cellular changes associated with progeria are perm
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Source:NIH


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