Protein Causing ‘Wrinkly Skin Syndrome’ Could Be Key Target In Anti-Ageing Developments

« Maintaining skin youthfulness could be possible through targeting enzymes after it was found that the mutation of a novel protein results in a rare premature ageing condition, and this could shed light on the underlying mechanisms of skin ageing.


Scientists from Agency for Science, Technology and Research (A*STAR)’s Institute of Medical Biology (IMB) found that the P5CS protein mutation results in the skin ageing condition, and that this can also shed light on the underlying mechanisms of skin ageing, leading to a targeted skin rejuvenation products.

Given the size of the global anti-ageing market, this area is a key focus for cosmetics companies, and this discovery identifies a novel target for the development of wrinkle-defying treatments, and improvement of the skin’s self-renewal capacity and youthful appearance.

« By looking at rare disorders, we have successfully identified proteins critical to normal skin ageing. This discovery has opened up new possibilities in the fields of skin and ageing research, with crucial clinical implications,” says Professor Birgit Lane, Executive Director of IMB.

“We will continue to explore rare diseases with the dual aims of changing the lives of rare disorder patients, and improving the scientific understanding of common conditions to help the general public. »

‘Wrinkly skin syndrome’

The condition in question which was studied is De Barsy syndrome (DBS), otherwise known as ‘wrinkly skin syndrome’, which is a rare autosomal recessive genetic disorder that can lead to loose hanging skin and premature ageing.

The researchers discovered that in this condition, a unique mutation in the enzyme P5CS affecting only the residue Arg138, was the cause for the observed symptoms and a prematurely-aged appearance.

Having identified this, scientists say they can now develop treatments to counteract P5CS mutations, and therefore hope to recover skin elasticity.

The team were drawn to this research, published in the American Journal of Human Genetics , after a previous study in 2009 found that mutation of the PYCR1 gene was an underlying cause of DBS, making PYCR1 a prime target for anti-wrinkling treatments for common disorders related to ageing.

In these patients’ cases, while they showed DBS-like symptoms, their PYCR1 genes did not bear any mutations, suggesting that other genes could be responsible.


So the A*STAR research team set about investigating this, collaborating with over 16 hospitals and research centres across 11 countries, by examining the DNA samples of patients with suspected De Barsy Syndrome (DBS), and finding the novel protein mutation as the cause.

As people age, skin tends to become thinner, more fragile, and lacking in elasticity, leading to wrinkles, so the A*STAR team sees no reason why this latest understanding cannot be the first step to slowing down the effects.

IMB and IMCB Senior Principal Investigator Dr Bruno Reversade, one of the study’s corresponding authors, commented, « We are now certain that skin ageing in humans is under the control of proline metabolism, which both PYCR1 and P5CS are involved in. Our next challenge is to find out if these two enzymes are druggable to develop active compounds to slow down the effects of ageing. »

Article of Andrew McDougall

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