Research Paper|Volume 8, Issue 2|pp 382—393

Telomere shortening leads to earlier age of onset in ALS mice

Birgit Linkus¹, Diana Wiesner¹, Martina Meßner¹, Alexander Karabatsiakis², Annika Scheffold³, K. Lenhard Rudolph⁴, Dietmar R. Thal⁵, Jochen H. Weishaupt¹, Albert C. Ludolph¹, Karin M. Danzer¹

¹Department of Neurology, Ulm University, 89081 Ulm, Germany
²Department of Clinical & Biological Psychology, Ulm University, 89081 Ulm, Germany
³Department of Internal Medicine III, Ulm University, 89081 Ulm, Germany
⁴Leibniz Institute for Age Research, 07745 Jena, Germany
⁵Department of Pathology, Ulm University, 89081 Ulm, Germany

§ Current address: KU Leuven, Department of Neuroscience, B-3000 Leuven, Belgium

Received: December 23, 2015Accepted: January 27, 2016Published: February 24, 2016

https://doi.org/10.18632/aging.100904

Copyright: © 2016 Linkus et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Telomere shortening has been linked to a variety of neurodegenerative diseases. Recent evidence suggests that reduced telomerase expression results in shorter telomeres in leukocytes from sporadic patients with amyotrophic lateral sclerosis (ALS) compared with healthy controls. Here, we have characterized telomere length in microglia, astroglia and neurons in human post mortem brain tissue from ALS patients and healthy controls. Moreover, we studied the consequences of telomerase deletion in a genetic mouse model for ALS. We found a trend towards longer telomeres in microglia in the brains of ALS patients compared to non-neurologic controls. Knockout of telomerase leading to telomere shortening accelerated the ALS phenotype in SOD1^G93A–transgenic mice. Our results suggest that telomerase dysfunction might contribute to the age-related risk for ALS.