Priority Research Paper Volume 11, Issue 10 pp 2916—2948
Telomerase gene therapy ameliorates the effects of neurodegeneration associated to short telomeres in mice
- 1 Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid 28029, Spain
- 2 Unit of Murine and Comparative Pathology (UPMiC), Department of Animal Medicine and Surgery, Veterinary Faculty, Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Barcelona, Spain
- 3 Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Barcelona, Spain
- 4 Center of Animal Biotechnology and Gene Therapy, Department of Animal Medicine and Surgery, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
- 5 Center of Animal Biotechnology and Gene Therapy, Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
received: April 26, 2019 ; accepted: May 17, 2019 ; published: May 28, 2019 ;https://doi.org/10.18632/aging.101982
How to Cite
Copyright © 2019 Whittemore et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Neurodegenerative diseases associated with old age such as Alzheimer’s disease present major problems for society, and they currently have no cure. The telomere protective caps at the ends of chromosomes shorten with age, and when they become critically short, they can induce a persistent DNA damage response at chromosome ends, triggering secondary cellular responses such as cell death and cellular senescence. Mice and humans with very short telomeres owing to telomerase deficiencies have an earlier onset of pathologies associated with loss of the regenerative capacity of tissues. However, the effects of short telomeres in very low proliferative tissues such as the brain have not been thoroughly investigated. Here, we describe a mouse model of neurodegeneration owing to presence of short telomeres in the brain as the consequence of telomerase deficiency. Interestingly, we find similar signs of neurodegeneration in very old mice as the consequence of physiological mouse aging. Next, we demonstrate that delivery of telomerase gene therapy to the brain of these mice results in amelioration of some of these neurodegeneration phenotypes. These findings suggest that short telomeres contribute to neurodegeneration diseases with aging and that telomerase activation may have a therapeutic value in these diseases.