Effects of aging on nitrergic neurons in human striatum and subthalamic nucleus

Santos‐Lobato, Bruno Lopes; Del‐Bel, Elaine; Pittella, José Eymard Homem; Tumas, Vítor

doi:10.1590/0004-282x20150097

Cited by 1 publication

(1 citation statement)

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“…Previous studies did not find age‐related telomere attrition in human neuronal and glial cells across the adult age range in healthy controls but identified significantly shorter telomeres in glial cells compared with neurons (Tomita et al, 2018 ). Stereology studies consistently reported decreasing number of oligodendrocytes but not neurons with advancing age in the human neocortex (Fabricius et al, 2013 ; Pelvig et al, 2008 ), striatum and putamen (dos Santos‐Lobato et al, 2015 ; Selden et al, 1994 ). Similarly, changes in cell‐type‐specific gene expression did not indicate a decrease in neuronal markers with age (Soreq et al, 2017 ).…”

Section: Discussionmentioning

confidence: 98%

Age‐related telomere attrition in the human putamen

et al. 2023

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Age is a major risk factor for neurodegenerative diseases. Shortening of leucocyte telomeres with advancing age, arguably a measure of “biological” age, is a known phenomenon and epidemiologically correlated with age‐related disease. The main mechanism of telomere shortening is cell division, rendering telomere length in post‐mitotic cells presumably stable. Longitudinal measurement of human brain telomere length is not feasible, and cross‐sectional cortical brain samples so far indicated no attrition with age. Hence, age‐related changes in telomere length in the brain and the association between telomere length and neurodegenerative diseases remain unknown. Here, we demonstrate that mean telomere length in the putamen, a part of the basal ganglia, physiologically shortens with age, like leukocyte telomeres. This was achieved by using matched brain and leukocyte‐rich spleen samples from 98 post‐mortem healthy human donors. Using spleen telomeres as a reference, we further found that mean telomere length was brain region‐specific, as telomeres in the putamen were significantly shorter than in the cerebellum. Expression analyses of genes involved in telomere length regulation and oxidative phosphorylation revealed that both region‐ and age‐dependent expression pattern corresponded with region‐dependent telomere length dynamics. Collectively, our results indicate that mean telomere length in the human putamen physiologically shortens with advancing age and that both local and temporal gene expression dynamics correlate with this, pointing at a potential mechanism for the selective, age‐related vulnerability of the nigro‐striatal network.

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