Scientists Uncover Exciting Lead into Premature Ageing and Heart Disease

This research was done by A*STAR's Institute of Medical Biology (IMB) in collaboration with their partners at the National Institute of Allergy and Infectious Diseases in the United States and the Institute of Cellular and System Medicine in Taiwan. Their findings were published in the prestigious scientific journal, Cell, on 27th April 2012 and provide an exciting lead into developing new methods to treat premature aging and heart disease.

Children with progeria suffer symptoms of premature ageing and mostly die in their early teens from either heart attack or stroke. 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 making it harder for the heart to pump blood and deliver it 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. SUN1 is a protein also found in the inner nuclear membrane, but there have been no previous studies to show how SUN1 interacts with the Lamin proteins.

The scientists wanted to investigate if SUN1 had any involvement in diseases caused by mutations in Lamin A, so they inactivated SUN1 in mouse models developed for progeria and AD-EDMD. These mouse models for progeria and AD-EDMD usually thrive poorly and have markedly short life spans as they die from premature ageing and heart failure respectively. However, by inactivating SUN1 and reducing SUN1 levels in these mouse models, the scientists observed that the life spans of the mouse models for progeria and AD-EDMD 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. This is the first time that Sun1 protein has been implicated in diseases linked to Lamin A and it is exciting how basic research has led to a discovery that can potentially have significant impact on us,” said Rafidah Abdul Mutalif, who is pursuing her PhD at IMB and one of the main authors of this paper.

Prof. Colin Stewart, Principle 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. 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. We are very excited about this discovery and look forward to further pursuing this lead which could potentially lead to development of new treatments for heart diseases.”

Notes for editor:
The research findings described in this news release can be found in the 27 Apr issue of Cell, Chen, C-Y et al 2012 Accumulation of the Inner Nuclear Envelope Protein Sun1 Is Pathogenic in Progeric and Dystrophic Laminopathies Cell 149.

About the Institute of Medical Biology (IMB)

IMB is one of the Biomedical Sciences Institutes of the Agency for Science, Technology and Research (A*STAR). It was formed in 2007, the 7th and youngest of the BMRC Research Institutes, with a mission to study mechanisms of human disease in order to discover new and effective therapeutic strategies for improved quality of life. From 2011, IMB also hosts the inter-research institute Skin Biology Cluster platform. IMB has 20 research teams of international excellence in stem cells, genetic diseases, cancer and skin and epithelial biology, and works closely with clinical collaborators to target the challenging interface between basic science and clinical medicine. Its growing portfolio of strategic research topics is targeted at translational research on the mechanisms of human diseases, with a cell-to-tissue emphasis that can help identify new therapeutic strategies for disease amelioration, cure and eradication. For more information about IMB, please visitwww.imb.a-star.edu.sg.

About A*STAR

The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity. A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, and with other local and international partners. For more information about A*STAR, please visitwww.a-star.edu.sg.

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