The report has been published in the International Journal of Epidemiology; an international study of twins led by King’s College London highlights how a technique called metabolomic profiling has revealed a collection of 22 metabolites – chemical fingerprints left behind as a result of early molecular changes before birth or in infancy – 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 metabolite, which may be determined in the womb and affected by nutrition during development, could reflect accelerated ageing in later adult life.
Scientists believe that 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.
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“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 birth weight are more susceptible to age related diseases”, said Professor Tim Spector, Head of the Department of Twin Research at King’s College London.
“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.” Added Spector.
Funded by the European Commission, researchers from 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 6000 twins, they identified 22 metabolites directly linked to chronological age. The concentrations of the metabolites were higher in older people than in younger people.
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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.
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 birth weight 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.
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Ana Valdes, lead researcher from King’s, said that “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,” she said.
“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,” she said.
“This shows us that birth weight 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.”