Scientists in Hong Kong have shed new light on why cell repair is less efficient in older people after a breakthrough discovery on premature aging, a rare genetic disease that affects one in four million babies.
Premature aging, or Hutchison-Gilford Progeria Syndrome (progeria), is obvious in the appearance of a child before it is a year old. Although their mental faculties are normal, they stop growing, lose body fat and suffer from wrinkled skin and hair loss.
Like old people, they suffer stiff joints and a buildup of plaque in arteries which can lead to heart disease and stroke. Most die of cardiovascular diseases before they are 20.
In 2003, a team of scientists in the United States found that progeria was caused by mutation in a protein called Lamin A, which lines the nucleus in human cells.
A team at the University of Hong Kong, led by Zhou Zhongjun, took the research a step further in 2004 and found that mutated Lamin A actually disrupted the repair process in cells, thus resulting in accelerated aging.
The study was published in the July issue of the Nature Medicine journal.
Zhou said the team came by their findings after comparing skin cells taken from two progeria sufferers, normal humans, progeria mice and normal mice.
While damaged DNA was quickly repaired in the healthy human and mice cell samples, the samples taken from the progeria humans and mice had difficulty repairing damaged DNA.
“Mutation in this protein (Lamin A) can cause defects in repair and thus lead to progeria,” Zhou, a research assistant professor with the biochemistry department at the University of Hong Kong, said in an interview.
“DNA damage is not effectively repaired in cells with defective Lamin A but very efficiently repaired in normal cells.”
The study highlights the importance of Lamin A to the repair process, and any mutation to Lamin A that disrupts repair will bring about aging, Zhou said.
Applying to cancer cells
Having established the link between Lamin A and repair, Zhou is using major findings from other research he did in 2002 to work on his next project, a product which he hopes could kill cancer cells.
Zhou, Professor Karl Tryggvason in Sweden’s Karolinska Institute and a Spanish research group found in 2002 that the enzyme Zmpste 24 was responsible in converting prelamin A to functional Lamin A.
Zhou’s laboratory is now developing inhibitors to Zmpste 24, which he hopes to apply to tumors. These inhibitors should theoretically disrupt Lamin A production, thwart the repair function in cancer cells, and bring on their premature aging and death.
“We’re now trying to develop inhibitors to Zmpste 24 and apply it to tumor cells,” he said.
