S'pore scientists discover lead into premature ageing disease

SINGAPORE - Singapore scientists have discovered the secret to dramatically increasing the life span of sufferers of premature ageing disease and muscular dystrophy-linked heart disease.

Children with progeria (premature ageing disease) rapidly age and most die in their early teens from either heart attacks or strokes.

Individuals with Emery-Dreifuss muscular dystrophy (AD-EDMD) suffer from muscle wasting and cardiomyopathy - a type of heart disease that weakens and enlarges the heart muscle.

This results in the heart having to work harder to pump blood to the rest of the body, leading to heart failure.

Both diseases are caused by mutations in Lamin A, a protein in the membrane surrounding a cell's nucleus which provides mechanical support to the nucleus.

The research, conducted at A*STAR's Institute of Medical Biology (IMB), revealed that the lifespans of mice with the mutations could be dramatically increased by reducing levels of a protein called SUN1, found in the inner nuclear membrane.

By inactivating the protein in mice suffering from progeria and AD-EDMD, scientists observed that the life spans of the affected mice doubled and tripled respectively.

"We actually expected that knocking out SUN1 in these mouse models would worsen their conditions and cause them to die faster, but surprisingly we observed the opposite," said Rafidah Abdul Mutalif, one of the main authors of this paper.

Prof Colin Stewart, Principal Investigator at IMB, said: "Notably, the heart muscle of the mice was restored to near normal function and cardiac function improved when the levels of SUN1 were reduced."

He added that mutations in Lamin A are frequently reported as a cause of heart disease, and especially within a group of hereditary cardiomyopathies.

"This opens up a possibility that from these observations, reduction in SUN1 maybe of therapeutic use for other forms of heart disease," he said, highlighting that pursuing this lead could potentially lead to the development of new treatments for heart diseases.

The findings, published in scientific journal 'Cell', was in collaboration with the National Institute of Allergy and Infectious Diseases in the US and the Institute of Cellular and System Medicine in Taiwan.