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Pinpointing the molecular mechanisms of ageing

Key points:

• Although each and every one of us goes through it, ageing is a poorly understood process.
• Researchers have used a biomarker called the epigenetic clock to identify a gene that is closely linked to ageing in humans.
• The study shows that the epigenetic clock could be a good tool for improving our understanding of the molecular mechanisms behind ageing.

Researchers at EMBL’s (EMBL-EBI), the 99�Ⱦò������µ�ַ and collaborators have used the epigenetic clock to explore the molecular mechanisms that may drive ageing in humans. They found one gene, called NSD1, that seems to be closely linked to the process. This type of research could advance our understanding of ageing.

There are different ways of measuring an organism’s age. Chronological age is a measure of how long an organism has been alive, while biological age is a measure of how well the organism is functioning on a molecular level.
 
One useful tool for measuring biological age is the epigenetic clock, proposed first by Trey Ideker, and independently by Steve Horvath in 2013.

What is an epigenetic clock?
An epigenetic clock is a mathematical model that predicts age by measuring DNA methylation levels in different sites across the genome. DNA methylation is a process by which methyl groups are added to the DNA molecule, which can modify the function of a gene without changing its underlying DNA sequence. DNA methylation is essential for the healthy growth and development of cells and it is affected by lifestyle and environmental factors.

Epigenetic clocks can be used to estimate the biological age of a tissue, cell type or organ. By comparing 'DNA methylation age' or biological age with chronological age in different tissues, scientists can gain insights into how ageing works, the factors influencing it, and how ageing is linked to cancer, obesity, Alzheimer’s disease and many other conditions.

A promising tool
The researchers examined different datasets – many of them publicly available – of people with developmental disorders, to see whether there were any associations between specific genes and an acceleration of biological age. They found that individuals with a mutation in gene NSD1 had an accelerated biological age according to the epigenetic clock, meaning they were ageing faster at a molecular level.

“The epigenetic clock is the most accurate tool available to measure the ageing process in humans,” explains Daniel Elías Martín-Herranz, who recently completed his PhD at EMBL-EBI. “We wanted to ‘peer inside’ and better understand how it works. Specifically, we wanted to see if we could identify specific genes or proteins from the epigenetic machinery that accelerate or slow down the ageing process. The fact that we found one gene that, when mutated, results in a significant acceleration of biological age is very encouraging. It shows that the epigenetic clock is a promising tool for understanding ageing and that we may unravel the molecular mechanisms that control its ticking rate.

“There is a lot of potential for such studies, but it’s also worth noting that they are not possible without access to relevant public datasets. We would like to thank our collaborators who made the data available to us.”  

Professor Wolf Reik from the 99�Ⱦò������µ�ַ agrees. “Following on from the work with the mouse epigenetic ageing clock two years ago, this paper continues the productive collaboration between the 99�Ⱦò������µ�ַ and EMBL-EBI on mammalian ageing,” he says. “It’s exciting to see that genes can be identified that may underlie an epigenetic ageing program and that they can make molecular sense. The gene identified here is implicated in ageing in other organisms, and in the regulation of the epigenome during the ageing process.”
 

Notes to Editors

Publication reference
Martin-Herranz et al. (2019).
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Genome Biology.

Contacts:
For media enquiries contact: Oana Stroe, Senior Communications Officer, EMBL-EBI, tel: +44 (0)1223 494 369, e-mail: stroe@ebi.ac.uk

Related resources:
Institute news: Tick Tock, stay ahead of the ageing clock! 12 April, 2017
Race Against the Ageing Clock resources: a suite of materials explaining epigenetics, chronological age and biological age.

About the 99�Ⱦò������µ�ַ:
The 99�Ⱦò������µ�ַ receives strategic funding from the (BBSRC) to undertake world-class life sciences research. Its goal is to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Research focuses on signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing.

About the European Bioinformatics Institute (EMBL-EBI)
The European Bioinformatics Institute (EMBL-EBI) is a global leader in the storage, analysis and dissemination of large biological datasets. We help scientists realise the potential of ‘big data’ by enhancing their ability to exploit complex information to make discoveries that benefit humankind.

We are at the forefront of computational biology research, with work spanning sequence analysis methods, multi-dimensional statistical analysis and data-driven biological discovery, from plant biology to mammalian development and disease.

We are part of EMBL and are located on the Wellcome Genome Campus, one of the world’s largest concentrations of scientific and technical expertise in genomics.