Adult stem cells may help explain what causes Hutchinson-Gilford Progeria Syndrome (HGPS), a rare disease that triggers premature aging in kids, a new study has found.
These findings, by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), are the first to indicate a biological basis for the clinical features of HGPS, also known as progeria.
It may also shed light on the biological mechanisms of normal aging.
"Studies like this of the biology of HGPS hold the potential to benefit children suffering this terrible illness and enlighten us as to the medical changes we all experience as we grow older," Nature quoted NCI Director John E. Niederhuber, M.D, as saying.
In 2003, scientists identified the cause of HGPS, a mutated protein called progerin, but the mechanism by which it causes the widespread clinical effects of the disease has been unclear.
In the current study, Tom Misteli and Paola Scaffidi at NCI looked at the effects of progerin on gene expression in a laboratory model of HGPS.
They found that progerin turns on genes involved in the Notch signalling pathway, a major regulator of stem cell differentiation, the process by which stem cells give rise to the mature cells that make up different tissues.
Since most of the tissues affected by HGPS arise from a common developmental pathway, the researchers examined the effects of progerin on adult mesenchymal stem cells - the common cellular ancestor of these tissue types.
An adult stem can repair itself, and can distinguish to yield the major specialized cell types of the tissue or organ.
The researchers' experiments showed that progerin profoundly affects the fate of these stem cells, greatly skewing the rate at which they mature into different tissues.
For example, progerin-producing stem cells showed accelerated maturation into bone but failed to develop into fat.
According to researchers, this could explain two of the distinguishing clinical features of HGPS: abnormal bone growth and an almost complete loss of the fatty tissues normally found just beneath the skin.
The researchers were able to copy the progerin's effects in these stem cells by experimentally turning on the same components of the Notch pathway targeted by progerin.
The findings of the study offer a new window into the biology behind the clinical features of HGPS and they may also hold relevance for understanding the biology of normal aging.
"Progerin is present at low levels in the cells of healthy people. One could envision a scenario in which progerin's effects on the Notch pathway and, by extension, on adult stem cells could, over time, lead to many of the tissue changes we commonly associate with the aging process," Misteli said.
The study is published in the March, 2008, issue of Nature Cell Biology.