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Biomedicine and digital

Isabelle Kling - 29/01/2019

The passing years also take their toll on telomeres

Telomere - ©AJC1 - CC BY-SA 4.0

A new mathematical tool developed by Anne Gegout-Petit, Head of the BIGS project team, and Denis Villemonais, a researcher on the TOSCA project team, is opening up new opportunities for research into the genetic causes of ageing.

New field of exploration for genetic

The passing years take their toll on our bodies, but also on the length of our telomeres. These short sequences of DNA situated at both ends of our chromosomes protect them from damage that might be caused when cells multiply. For a long time, however, biologists have known that their length diminishes during the course of our lives, and that this shrinkage is linked to the appearance of certain cardiovascular and neurodegenerative, age-related diseases.

Anne Gegout-Petit and Denis Villemonais have collaborated with the team of Athanase Benetos, Head of the Department of Geriatrics at Nancy Regional University Hospital (CHRU), on the development of a new statistical tool enabling the analysis of telomere length in a much more accurate and detailed manner than before. In this way, statistics are opening up a whole new field of exploration in genetics.

Traditionally, biologists have only considered the mean length of a person’s telomeres, which is relatively easy to obtain: after blood sampling, the person’s DNA is extracted from the cells and the telomeres can then be specifically measured. Unfortunately, the calculation of this mean value obscures any distinctive features that might exist; however, the more precise biological analysis technique providing the distribution of the telomere lengths that is associated with this new statistical analysis technique reveals these distinctive features. This makes it possible to assess their importance.

Unique telomeric signature

Each human cell contains 92 telomeres, i.e. one at each end of the 46 chromosomes. Each of these telomeres is likely to differ in length. They are usually between 3 and 20 kilobases (1 base is one of the building blocks that make up DNA): the range of possible lengths therefore covers all possible values between 3 and 20. The graphical representation of this distribution is a bell curve whose exact shape varies from one person to another.

The statistical analysis carried out by Anne Gegout-Petit and Denis Villemonais has enabled researchers to analyse the distributions of the telomere lengths of 72 people, based on blood samples taken at 8 to 10-year intervals. The researchers observed that this distribution, i.e. the bell curve of the graph, was particular to each person. This means that we all have our own specific telomeric signature!

Visualization of threshold effects

Therefore, at 8 to 10-year intervals, the distribution curve for our telomere lengths remains statistically constant for a given person, even though it changes as the lengths become shorter. However, this distribution is statistically different from one person to another, even for people of the same age.

This surprising discovery opens up new opportunities for the study and understanding of ageing. This much more accurate statistical analysis reveals threshold effects that were impossible to observe by studying the mean lengths. Scientists now hope to understand whether the signs of ageing only appear when a certain number of telomeres drop below a critical minimum length threshold. The passing years may affect certain telomeres differently and still have devastating effects…

The telomere length distribution curves today (red) and 8 years ago (black) are superimposed for the same person on each occasion but differ between each person. - ©Nature

Keywords: Tosca Genetic Bigs Interdisciplinarity Statistics Inria Nancy - Grand Est centre

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