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Shortening of leucocyte telomeres with advancing age, arguably a measure of \u201cbiological\u201d age, is a known phenomenon and epidemiologically correlated with age\u2010related disease. The main mechanism of telomere shortening is cell division, rendering telomere length in post\u2010mitotic cells presumably stable. Longitudinal measurement of human brain telomere length is not feasible, and cross\u2010sectional cortical brain samples so far indicated no attrition with age. Hence, age\u2010related 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\u2010rich spleen samples from 98 post\u2010mortem healthy human donors. Using spleen telomeres as a reference, we further found that mean telomere length was brain region\u2010specific, 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\u2010 and age\u2010dependent expression pattern corresponded with region\u2010dependent 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\u2010related vulnerability of the nigro\u2010striatal network.<\/jats:p>","DOI":"10.1111\/acel.13861","type":"journal-article","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T12:48:33Z","timestamp":1683031713000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Age\u2010related telomere attrition in the human putamen"],"prefix":"10.1111","volume":"22","author":[{"given":"Sebastian R.","family":"Schreglmann","sequence":"first","affiliation":[{"name":"Queen Square Institute of Neurology University College London  London UK"},{"name":"Department of Neurology University Hospital W\u00fcrzburg  W\u00fcrzburg 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