Breakthroughs in progeria research
Progeria, (officially, "Hutchinson-Gilford Progeria Syndrome"), is a rare fatal disease that makes the victim appear, as the name suggests, prematurely old. Although these children are born looking healthy, onset of the disease occurs around 12-24 months, affecting about 1 out of 4 million children. Symptoms include growth failure, hair loss, and other diseases of aging: atherosclerosis and stroke, arthritis, hip dislocation, aged-looking skin. Most children die of heart disease by the age of 13; life expectancy averages between 8-21 years. (A marked contrast to the story of Brooke Greenberg, a 12-year-old who still looks like an infant).First described over a hundred years ago, progeria is caused by a mutation in the LMNA gene. This gene produces the Lamin A protein, which is the structural scaffolding that holds the nucleus of a cell together. It's thought that this mutation makes the nucleus unstable, leading to premature aging seen clinically. It was reported earlier this year that a class of anti-cancer drugs called farnesyltranferase inhibitors may help children with this condition. In tissue culture, these drugs finish a job that is blocked in progeria patients--snipping off a farnesyl group thought to somehow "gum up the works" in the cell and lead to progeria. Now, new research suggests possible reasons for this "gumming."
One study found that some of the lamins turn up in the wrong place—too tightly linked to the membranes of the nuclear envelope to participate properly in key stages of cell replication.It's often said that funding for research is unbalanced. Why do we spend so much money on a disease that only affects a relatively few people? Why isn't more money spent on heart disease and stroke, leading killers in the U.S., for example? If heart disease causes, say, a third of all deaths, shouldn't it get a third of the research dollars? This case shows why it shouldn't be quite that simple. Progeria is a rare disease, affecting only a handful of children in this country--but research in this area may lead not only to treatment and/or prevention of progeria, but also to a better understanding of the molecular mechanisms that cause us all to age. You simply don't know where the next brilliant insight is going to come from, whether it be specific disease-related research, or your morning breakfast cereal.
The researchers said this would disrupt DNA replication, and be a likely factor in the rapid march of cells toward premature “senescence,” a cellular version of aging. Whether similar missteps and miscues by nuclear lamins are part of normal human aging is the question that draws researchers onward, said Goldman. But the findings are consistent with a widespread belief among biologists that a key cause of ordinary aging is damage to DNA and mistakes in gene replication, two interrelated problems.
Another study found that the most common type of mutant lamin re-organizes regions of chromosomes that are key in controlling gene expression. These portions of chromosomes, known as heterochromatic regions, are kept inactive for various reasons; for example, one of the two female X chromosomes is deactivated in this fashion in order to avoid having them duplicate their work.
One of the hallmarks of the X chromosome heterochromatic region is that it is linked to molecules known as methylated histones. But the researchers found that in a girl with the progeria syndrome, the quantities of these molecules and of an enzyme required to form them were abnormally low.
