Telomeres Shorten with Age in Rat Cerebellum and Cortex in vivo

Flanary, Barry E.; Streit, Wolfgang J.

doi:10.1089/109454503323028894

Cited by 85Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsChromosomal and Genetic Variations

Telomeres Shorten with Age in Rat Cerebellum and Cortex in vivo

Flanary, Barry E., Streit, Wolfgang J.·2003·Journal of Anti-Aging Medicine

DOI 10.1089/109454503323028894

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Abstract

Normal somatic cells have a finite replicative capacity. With each cell division, telomeres, the ends of linear chromosomes, progressively shorten until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain their telomeres by the action of the telomerase enzyme. Glia, particularly microglia, are the only adult cell type in the central nervous system (CNS) that exhibit a significant mitotic potential, and are thus susceptible to telomere shortening. Previous research in our laboratory has found that telomeres shorten in rat microglia with increasing time in vitro. Our current hypothesis is that telomeres shorten in rat brain in vivo with increasing age. Tissue samples of cerebellum and cortex were obtained from Sprague-Dawley rats of various ages. Genomic DNA and total protein was isolated from each sample for telomere length measurement via Southern blot analysis (up to 5 months) and telomerase activity measurement via TRAP analysis (up to 6 months), respectively. Telomere shortening occurs in vivo in both rat cerebellum and cortex from day 21 to approximately 5 months of age. Cortex samples possessed shorter telomeres than did cerebellum samples. The longest telomeres undergo the most dramatic shortening, while the shortest telomeres exhibit only slight attrition. Telomerase activity slowly increases from day 21 to approximately 6 months of age, with the cerebellum exhibiting higher activity than cortex in all instances. These results indicate that telomere shortening occurs in rat brain in vivo with increasing age, and that the low levels of telomerase activity present may be preferentially recruited to maintain the shortest telomeres while allowing the longer ones to shorten more rapidly. Since microglia are thought to be the only mature cells of the postnatal CNS undergoing appreciable cell division, we propose that the telomere shortening occurring in the adult rat brain with age can be largely attributed to microglial cell division. Our findings provide an impetus to further investigate the pattern of telomere length and telomerase activity that emerges with further aging in the rat brain.

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Associated with these morphological alterations are biochemical changes, such as elevated expression of antigen presentation molecules (MHCII), Toll-like receptors, pro-inflammatory cytokines (IL-1β), reduced expression of regulatory molecules (CX3CR1 and CD200R), DNA methylation changes and telomere shortening.
“Associated with these morphological alterations are biochemical changes, such as elevated expression of antigen presentation molecules (MHCII), Toll-like receptors, pro-inflammatory cytokines (IL-1β), reduced expression of regulatory molecules (CX3CR1 and CD200R) (Frank et al, 2006;Maher et al, 2004), DNA methylation changes and telomere shortening (Flanary and Streit, 2003;Zannas et al, 2015).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Flanary and Streit, 2003
Age-associated increase in telomerase activity and reduction in telomere length has been reported in the rat brain, indicating that microglia of the aged brain have a reduced potential for proliferation.
“Indeed, ageassociated increase in telomerase activity and reduction in telomere length has been reported in the rat brain (Flanary and Streit, 2003), indicating that microglia of the aged brain have a reduced potential for proliferation.”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Flanary and Streit, 2003

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Authors: Flanary, B. E., & Streit, W. J.
Affiliations: University of Florida Health (US)
ORCID: Streit, Wolfgang J.
Venue: Journal of Anti-Aging Medicine
Publisher: SAGE Publications
Published: 2003-12
Volume: 6
Issue: 4
Pages: 299-308
ISSN: 1094-5458 (ISSN-L)
DOI: 10.1089/109454503323028894
OpenAlex: W2055912973
Cited by: 85
References: 52
Citations by year: 2026: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 6 · 2015: 9 · 2014: 4 · 2013: 2 · 2012: 3
FWCI: 2.37
Type: journal article
Language: en
Open access: closed
Licence: www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations: Rejuvenation Research (publishedVersion)
PubMed (publishedVersion)
Funders: University of Florida
College of Medicine, University of Florida
Topics: Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords: telomere shortening, telomerase activity, brain aging, microglia, cerebellum, cerebral cortex, replicative senescence, rat brain
MeSH terms: Aging, Animals, Cerebellum, Cerebral Cortex, Telomere, Rats, Sprague-Dawley, Rats

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Telomeres Shorten with Age in Rat Cerebellum and Cortex in vivo

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