Singapore, Sep 2, 2009: Scientists from Singapore and Germany have made a novel discovery that might lead to ways of reversing the effects of ageing and wrinkled skin. The international team of scientists led by Dr Bruno Reversade from A*STAR’s Institute of Medical Biology (IMB) discovered that mutations in the PYCR1 gene cause a rare genetic condition which results in premature skin ageing, known as “wrinkly skin syndrome.”

Their findings, which are published in the 1 Sep 2009 print issue of the prestigious journal Nature Genetics, provide insight into how some unexpected genes help maintain youthful skin. This research project is said to have involved collaborations with over 15 hospitals and research centres in 13 countries.

 

Using bioinformatics tools, Dr Reversade and his team analyzed rare DNA samples collected from affected patients across the world who, at a young age, displayed signs of premature ageing. They identified the PYCR1 gene on chromosome 17 of these patients to be defective and found specific mutations in the gene that led to conditions often seen in elderly people, such as loose skin, loss of bone density, hip dislocation and cataract. Furthermore, they determined that skin and bone were the two tissues most severely affected in patients. As skin and bone contain high levels of the PYCR1 protein under normal circumstances, developing therapies that could increase the activity of the PYCR1 protein could possibly reverse the process of ageing in affected individuals or slow it down in normal people.

 

Dr Reversade said , “Our findings confirm the significance of mitochondrial function in the ageing process. They also unexpectedly highlight the importance of metabolism as PYCR1 is important in the synthesis of proline, a common amino acid involved in metabolism. Age-defying and anti-wrinkling treatments for common disorders related to ageing may also benefit from sustaining proline metabolism.”

The scientists also found that inside cells, the PYCR1 protein is located in the mitochondria. In their experiments, they observed changes in mitochondrial morphology and cell death in the connective tissues of individuals with PYCR1 mutations. They also conducted further investigations into the effects of reduced levels of PYCR1 protein by examining the growth of frog and fish models in which the PYCR1 gene had been experimentally shut off. They noted that mitochondrial function in the skin of the animal models was altered and there was also an increased occurrence of cell death.

Professor Birgit Lane, a skin biologist and Executive Director of IMB, said, “We are excited by these findings of Dr Reversade and colleagues, which open up new possibilities in the field of ageing and skin research. The study is a great example of scientific synergy – when clinicians and scientists from around the world come together to share their specialist skills and knowledge, they can discover new insights into complex medical conditions. Rare genetic disorders often provide surprising revelations. Pooling resources and targeting research to find new ways of combating disease – and benefiting people faster – is exactly what we try to do at IMB.”