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ACTRIMS 2021 | Leukocyte telomere length and disability in MS

The occurrence of telomere shortening with every cellular replication makes telomere length a strong marker of biological age. Leukocyte telomere length (LTL) is often used as an overall marker as it is representative of telomere shortening in other cell types and is easy to measure. Jennifer Graves, MD, PhD, MAS, University of California San Diego School of Medicine, San Diego, CA, discusses an investigation of LTL in a large cohort of patients with multiple sclerosis (MS) with over 10 years of follow-up to improve understanding of the relationship between age and disability in MS. At baseline, the results showed that shorter LTL was associated with higher expanded disability status scale (EDSS) scores. Additionally, matched-pair analysis was conducted to compare LTL in patients who went on to develop secondary progressive MS to those who did not. It was shown that patients with more telomere shortening over the 10-year follow-up developed secondary progressive MS more often. This interview took place during the ACTRIMS Forum 2021.

Transcript (edited for clarity)

Leukocyte telomere length is thought to be the ultimate biological clock. As cells replicate the telomeres, the protective caps at the end of chromosomes, shorten with each of those replication events. In all cell types throughout the body, telomeres can be used as this marker of biological age. Leukocyte telomere length is strongly associated with telomere length in other cells in the body so it’s commonly been used as an overall marker...

Leukocyte telomere length is thought to be the ultimate biological clock. As cells replicate the telomeres, the protective caps at the end of chromosomes, shorten with each of those replication events. In all cell types throughout the body, telomeres can be used as this marker of biological age. Leukocyte telomere length is strongly associated with telomere length in other cells in the body so it’s commonly been used as an overall marker. It’s easy to access in the blood, much easier than accessing biopsies from different tissues, particularly in the case of MS, tissues that we don’t want to biopsy in the central nervous system. It can be used as a marker of overall biological age in that individual.

We looked at telomere length in a large cohort of patients who had already been followed for 10 years and had stored samples. And what we found was that even at baseline in cross-sectional analysis, having shorter telomeres was associated with a clinically relevant, higher Expanded Disability Status Scale score, or disability score in MS. And it was also looked at how much of the association of chronological age is explained by telomere length. How much might be in that pathway in terms of determining the association of biological age and disability? And we found about 15% of the association of chronological age with disability seem to be explained, at least statistically, through leukocyte telomere length.

Then, we looked at a matched set of individuals. In that 10 years of follow-up, some patients developed secondary progressive MS. And some did not. And we matched people based on their baseline disability, their age, their gender, their disease duration. So they were very similar at baseline. And we looked at the ones that develop secondary progressive MS, and the ones who did not. The ones who had greater telomere attrition over those 10 years tended to be the ones that develop more disability and secondary progressive MS.

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