Rate of ageing may be determined in the womb and linked to birthweight, study reveals

Scientists have found that key metabolites in blood – chemical ‘fingerprints’ left behind as a result of early molecular changes before birth or in infancy – could provide clues to a person’s long-term overall health and rate of ageing in later life.

Published today in the International Journal of Epidemiology, the study of twins led by King’s College London highlights how a technique called metabolomic profiling has revealed a collection of 22 metabolites linked to ageing. One of these, linked to ageing traits such as lung function and bone mineral density, is also strongly associated with birthweight – a well-known developmental determinant of healthy ageing.

This finding suggests that levels of this novel metabolite, which may be determined in the womb and affected by nutrition during development, could reflect accelerated ageing in later adult life.

Scientists say the findings show it is possible that these markers of ageing can be identified with simple blood tests in the future, which may provide further clues to the ageing process and could pave the way for development of therapies to treat age-related conditions.

Professor Tim Spector, Head of the Department of Twin Research at King’s College London, said:  ‘Scientists have known for a long time that a person’s weight at the time of birth is an important determinant of health in middle and old age, and that people with low birthweight are more susceptible to age related diseases. So far the molecular mechanisms that link low birthweight to health or disease in old age had remained elusive, but this discovery has revealed one of the molecular pathways involved.’

Funded by the European Commission, Researchers from the Department of Twin Research at King’s carried out metabolomic profiling – the study of metabolites that specific cellular processes or changes leave behind in the blood. Analysing blood samples donated by over 6,000 twins, they identified 22 metabolites directly linked to chronological age – the concentrations of the metabolites were higher in older people than in younger people.

One particular metabolite – C-glyTrp – is associated with a range of age-related traits such as lung function, bone mineral density, cholesterol and blood pressure. Its role in ageing is completely novel.

Crucially, researchers found it was also associated with lower weight at birth when they compared the birth weights of identical twins. 

To explore the link between birthweight and the metabolite, the researchers showed via genetic tests that the gene influencing the levels could be modified epigenetically (whereby genes are switched on or off by chemical switches triggered by the person’s environment or lifestyle).  These epigenetic changes may then influence metabolism during a person’s lifetime, which in turn influences their risk of age-related diseases.

Ana Valdes, lead researcher from King’s, said: ‘Human ageing is a process influenced by genetic, lifestyle and environmental factors, but genes only explain a part of the story. Molecular changes that influence how we age over time are triggered by epigenetic changes. This study has for the first time used analysis of blood and epigenetic changes to identify a novel metabolite that has a link to birthweight and rate of ageing.

‘This unique metabolite, which is related to age and age related diseases, was different in genetically identical twins that had very different weight at birth. This shows us that birthweight affects a molecular mechanism that alters this metabolite. This may help us understand how lower nutrition in the womb alters molecular pathways that result in faster ageing and a higher risk of age-related diseases fifty years later.

‘Understanding the molecular pathways involved in the ageing process could ultimately pave the way for future therapies to treat age-related conditions. As these 22 metabolites linked to ageing are detectable in the blood, we can now predict actual age from a blood sample pretty accurately and in the future this can be refined to potentially identify future rapid biological ageing in individuals.’

For further information or a copy of the paper please contact Emma Reynolds, PR Manager (Health) at King’s College London, on 0207 848 4334 or email emma.reynolds@kcl.ac.uk

For further information about King’s visit our 'King’s in Brief' page.

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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

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