Genes that control 'ageing' steroid identified

Eight genes which control levels of the main steroid produced by the adrenal gland, believed to play a role in ageing and longevity, have been uncovered by an international consortium of scientists, co-led by King’s College London.

Crucially, some of these eight genetic regions are also associated with other important diseases of ageing, including type 2 diabetes and lymphoma. Researchers say that these findings, published in the journal PLoS Genetics today, provide the first genetic evidence for the ageing role of the steroid, and therefore highlights it as a marker of biological ageing. 

It was already known that the concentration of the steroid dehydroepiandrosterone sulphate (DHEAS), declines rapidly with age – it diminishes by 95 per cent by the age of 85. This has led to speculation that a relative DHEAS deficiency may contribute to common age-related diseases or diminished longevity.

To explore the mechanisms behind declining levels of the steroid, the researchers carried out an analysis of DHEAS levels and 2.5 million genetic variants in 14,846 people from Europe and USA. They found eight common genes that control the blood concentration of DHEAS, and importantly some of these genes are associated with ageing and common age-related diseases such as type 2 diabetes and lymphoma.

Lead author, Dr Guangju Zhai from King’s College London, said: ‘This is the first large-scale study to unlock the mystery that has always surrounded DHEAS. We have identified specific genes that control its concentration levels, and shown that some of these are also involved in the ageing process and age-related diseases.

‘The findings provide us with the basis for future studies to look into potential mechanisms of exactly how the DHEAS is involved in ageing.  The next important question to try and answer is whether sustained high levels of DHEAS can in fact delay the ageing process and prevent age-related diseases.’

Professor Tim Spector, senior co-author from King’s, said: ‘This study shows the power of collaborative genetic studies to uncover mechanisms of how the body works. For 50 years we have observed the most abundant circulating steroid in the body, DHEAS, with no clue as to its role. Now its genes have shown us its importance in many parts of the ageing process.’

Notes to editors

King's College London

King's College London is one of the top 25 universities in the world (2010 QS international world rankings), The Sunday Times 'University of the Year 2010/11' and the fourth oldest in England. A research-led university based in the heart of London, King's has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit:

www.kingshealthpartners.org.

For further information please contact Emma Reynolds, Press Officer at King’s College London, on 0207 848 4334 or email emma.reynolds@kcl.ac.uk

View the original article here

Key gene in breast cancer development identified

Researchers at King’s College London have identified a gene involved in the development of breast cancer, which could lead to the earlier detection and treatment of the disease.

A new study, in collaboration with Institut d'Investigació Biomédica de Bellvitge (IDIBELL), has found that gene changes occur up to five years before the detection of breast cancer, paving the way for treatments aimed specifically at reversing changes in susceptible genes before cancer occurs.

Breast cancer is the most common cancer in the UK with around 50,000 people diagnosed each year.

Published today in Carcinogenesis, the study was based on a group of 36 identical twin pairs from TwinsUK, based at King’s, the biggest adult twin registry in the UK, where one twin had developed breast cancer and the other had not. Comparing DNA samples from each twin, collected before and after the diagnosis of breast cancer, as well as samples from breast tumours and breast cancer cell lines, the research team found significant chemical changes in around 400 sites in the affected twin. Of these, scientists identified the DOK7 gene was identified as most likely to be directly involved in the development of breast cancer. On average, these chemical changes took place five years prior to the diagnosis of breast cancer.

Identical twins such as those at TwinsUK are ideal for studies of this nature as theyshare 100 per cent of their genes. Therefore, any difference between twins is attributable to environmental factors or chemical changes to their genes. These chemicalchanges in the way genes are expressed is called epigenetics.

Crucially, the DOK7 gene identified in this study can be switched on and off epigenetically, says Professor Tim Spector from the Department of Twin Research & Genetic Epidemiology at King’s, who co-authored the research paper.

Professor Spector said: ‘The identification of the DOK7 gene offers possibilities for the prediction and treatment of breast cancer and other common illnesses such as diabetes, Alzheimer’s disease and arthritis. In the future screening of epigenetic changes in key genes followed by drug treatments could be commonplace. Our twin studies are a great way of detecting these small but important differences between sisters and we hope to explore many other diseases.’

Dr Manel Esteller, Head of Epigenetics at IDIBELL, said: ‘An epigenetic alteration associated with an increased risk of breast cancer can be detected in the sick twin before theclinical diagnosis.’ The next step for researchers will be identifying the exact function of the DOK7 gene.

Dr Esteller added: ‘We believe the DOK7 gene is a regulator of tyrosine kinases, an antitumor drug target already used for the treatment of breast cancer. If DOK7 performs this function, new studies to test drugs for tumours resistant to chemotherapy could take place in the future.’

Notes to editors

Professor Tim Spector is available for interview.

Please contact Jack Stonebridge, PR Coordinator at King’s College London, on 0207 848 3238 or email jack.stonebridge@kcl.ac.uk

View the Carcinogenesis paper.

For further information on King’s visit our ‘King’s in Brief’ page.

For more information on the Epitwin project visit the website.

View the original article here