Research Paper Volume 10, Issue 11 pp 3397—3420
Cell cycle-dependent and -independent telomere shortening accompanies murine brain aging
- 1 Hans Berger Department of Neurology, Jena University Hospital, Jena, Thuringia 07747, Germany
- 2 Department of Internal Medicine II, Jena University Hospital, Jena, Thuringia 07747, Germany
- 3 Department of Internal Medicine III, Jena University Hospital, Jena, Thuringia 07747, Germany
- 4 Department of Internal Medicine I, Jena University Hospital, Jena, Thuringia 07747, Germany
- 5 Leibniz Institute on Aging – Fritz Lipmann Institute, 07745 Jena, Thuringia, Germany
- 6 Matthias Schleiden Institute for Genetics, Bioinformatics and Molecular Botany, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, Thuringia 07745, Germany
received: March 23, 2018 ; accepted: November 15, 2018 ; published: November 20, 2018 ;https://doi.org/10.18632/aging.101655
How to Cite
Copyright: Ain et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Replication-based telomere shortening during lifetime is species- and tissue-specific, however, its impact on healthy aging is unclear. In particular, the contribution of telomere truncation to the aging process of the CNS, where replicative senescence alone fails to explain organ aging due to low to absent mitotic activity of intrinsic populations, is undefined. Here, we assessed changes in relative telomere length in non-replicative and replicative neural brain populations and telomerase activity as a function of aging in C57BL/6 mice. Telomeres in neural cells and sub-selected neurons shortened with aging in a cell cycle-dependent and -independent manner, with preponderance in replicative moieties, implying that proliferation accelerates, but is not prerequisite for telomere shortening. Consistent with this telomere erosion, telomerase activity and nuclear TERT protein were not induced with aging. Knockdown of the Rela subunit of NF-κB, which controls both telomerase enzyme and subcellular TERT protein allocation, did also not influence telomerase activity or telomere length, in spite of its naive up-regulation selectively under aging conditions. We conclude that telomere instability is intrinsic to physiological brain aging beyond cell replication, and appears to occur independently of a functional interplay with NF-κB, but rather as a failure to induce or relocate telomerase.