Shortened telomeres linked to heart damage in Duchenne muscular dystrophy

Courtesy of Dr. Edwin P. Ewing, Jr. and the CDC

Stanford University researchers have pinpointed the progressive shortening of telomeres as a potential cause of the weakened hearts that kill many people with Duchenne muscular dystrophy. The discovery opens the door to possible new therapies for the genetic disorder.

Duchenne is caused by mutations in the gene dystrophin, which blocks the production of a protein of the same name. Lack of the dystrophin protein in muscle cells causes them to be fragile and easily damaged.

Telomeres--the caps at the ends of chromosomes--shorten every time a cell divides. But heart cells rarely divide, which makes the progressive shortening of telomeres in this case“particularly surprising,” the scientists said in a statement. Lead author Alex Chang looked at telomere length in mice that did not produce dystrophin at various points after birth: one, four, eight and 32 weeks. While the heart muscle cells stopped dividing at the one-week mark, Chang found that the telomeres kept dividing, eventually losing almost 40% of their length by the 32-week point.

The telomere shortening was linked to increasing levels of a protein, P53, which blocks the expression of two other proteins, ultimately inhibiting mitochondrial function, according to the statement.

"The decrease in the levels of these mitochondrial master regulators led to a reduction in the number of mitochondria in the cell and mitochondrial dysfunction," said Helen Blau, a professor of microbiology and immunology at Stanford, in the statement. "They make less of the energy molecule ATP and have higher levels of damaging reactive oxygen species. This is what leads to the cardiomyopathy that eventually kills the mice."

The researchers plan to look into how exactly lack of dystrophin plays a role in telomere shortening in heart muscle cells. They also want to find out if artificially lengthening telomeres could stave off heart damage in mice.

"More research is clearly needed before we attempt to devise any new therapies for humans," Blau said. "But these findings highlight the important role telomeres play in this and possibly many other human diseases in nondividing tissues like neurons and heart muscle."