Atherosclerosis: in the Hands of Fate... and Telomeres

Science

Telomeres are DNA sequences that protect the tips of our chromosomes. Unfortunately, they grow shorter over time. Can we prevent such wear and limit the associated cellular aging? It’s not that simple. A recent study on atherosclerosis just shattered this widely held hope.

Research on telomeres has been dynamic ever since their role in maintaining the integrity of the genome was discovered twenty years ago. Yet our knowledge remains spotty. “We know that telomere wear can reach a threshold that causes the cell to enter senescence. This unstable state can open the door to degenerative illnesses and cancer,” explains Athanase Bénétos, head of geriatrics at the Nancy university hospital, university professor, and Inserm researcher*. “We also know that short telomeres increase the risk of age-related illness, such as atherosclerosis.

Understanding why this happens is key. There are two hypotheses on the subject: “The reigning concept is that short telomeres are the result of attrition, or wear-and-tear over time. If this is the case, we could come up with a way to prevent it to limit the consequences. But our research is leading us to embrace another hypothesis, in which the length of our telomeres is largely determined after the first years of life,” adds the researcher.

To confirm this, Bénétos and his team studied the prognosis of atherosclerosis according to the changes in telomere length over time. Their conclusion was that the onset of vascular disease could be associated with short telomeres, and that the impact of attrition is negligible. Consequently, leading a healthy lifestyle is not thought to keep telomeres from wearing down or to limit the consequences of this, as the phenomenon is determined before adulthood.

The key time is before age 20

These results, which were recently published in Hypertension, were obtained by analyzing the data from a cohort monitoring the evolution of arterial rigidity in 154 adults aged 31 to 76. The subjects of the study presented with atherosclerosis at the start of the study or developed it during the course of monitoring. A third group made up of healthy volunteers (with no atherosclerosis, either at the start or end of the study) was used as a control group. For each participant, the team compared the analysis of two blood samples: the first was taken at the start of the study, and the second was taken 9.5 years afterward on average. The researchers measured the length of telomeres in their leukocytes (cells that are easy to analyze).

After the monitoring period, it became apparent that telomere attrition had not differed between patients with pre-existing atherosclerosis and the patients from the two other groups. However, those who had short telomeres upon inclusion had developed atherosclerosis by the end of the study more often than those who had long telomeres. “Patients with short telomeres had earlier and more severe atherosclerosis, while those with long telomeres had atherosclerosis that developed later on and was less extensive” according to Simon Toupance*, who conducted the analysis.

© Genome Research Limited

The strength of our study is that it is longitudinal, and that we used the most sensitive techniques possible, which allowed us to make solid conclusions,” he comments. “These data must be contrasted with those from transversal studies that are conducted with no point of comparison and that, as a result, cannot establish whether the observed phenomena are related to telomere length or to their attrition kinetic.”

Toupance concludes that “these results confirm that telomere length is indeed a biodeterminant of the development of degenerative diseases, and that this length is essentially determined genetically at birth, then over the course of the first years of life. Attrition during adulthood plays only a minor role.” Some studies suggest that a healthier lifestyle could limit telomeric attrition, but this is probably ineffectual. As a result, do we just give up? No, for two reasons: first of all, because “while a healthier lifestyle in adults does not determine telomere length, it reduces the risk of age-related cardiovascular disease, particularly in high-risk subjects. Subjects with short telomeres fall into that group.” And secondly, because “our results show that we need to further study the environmental factors that can be responsible for telomeric wear during the first years of our lives, particularly situations associated with high oxidative stress and chronic inflammation. Preventing such situations in children could have a highly beneficial effect on telomere length, and therefore on the risk of age-related illnesses.”

Notes

*Inserm unit 1116/University of Lorraine, Medical School, Vandoeuvre-les-Nancy

Source

Toupance S et al. Short Telomeres, but Not Telomere Attrition Rates, Are Associated With Carotid Atherosclerosis. Hypertension. 2017 Jun 19. pii: HYPERTENSIONAHA.117.09354. doi: 10.1161/HYPERTENSIONAHA.117.09354. 

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