Telomere-driven senescence accelerates tau pathology, neuroinflammation and neurodegeneration in a tauopathy mouse model

Sep 30, 2025Acta neuropathologica communications

Cell aging caused by telomere shortening speeds up tau buildup, brain inflammation, and brain cell loss in a mouse model of tau disease

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Abstract

The brains of 6- and 9-month-old Terc knockout mice show significant telomere attrition and signs of .

  • Cellular senescence is associated with increased tau phosphorylation at key residues in a mouse model.
  • The introduction of a senescent phenotype leads to enhanced tau truncation and aggregation over time.
  • Exacerbated activation of astrocytes and microglia is observed alongside tau pathology in the senescent context.
  • Selective neuronal loss occurs in vulnerable brain regions as a consequence of tau-related neurodegeneration.

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Key numbers

2.4ร—
Increase in
Measured in 9-month-old mice compared to mice.
30%
Neuronal Loss in
Observed in 9-month-old mice.

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