Can accelerated ageing models inform us on age‐related tauopathies?

Abstract

Ageing is the greatest risk factor of late‐onset neurodegenerative diseases. In the realm of sporadic tauopathies, modelling the process of biological ageing in experimental animals forms the foundation of searching for the molecular origin of pathogenic tau and developing potential therapeutic interventions. Although prior research into transgenic tau models offers valuable lessons for studying how tau mutations and overexpression can drive tau pathologies, the underlying mechanisms by which ageing leads to abnormal tau accumulation remains poorly understood. Mutations associated with human progeroid syndromes have been proposed to be able to mimic an aged environment in animal models. Here, we summarise recent attempts in modelling ageing in relation to tauopathies using animal models that carry mutations associated with human progeroid syndromes, or genetic elements unrelated to human progeroid syndromes, or have exceptional natural lifespans, or a remarkable resistance to ageing‐related disorders.

Premature aging in genetic diseases: what conclusions can be drawn for physiological aging

“…For CS ( Karikkineth et al, 2017 ; Han et al, 2023 ) and many types of XP ( Niedernhofer et al, 2011 ) the most severe pathology seems to be in the neuronal system resembling to some extent sporadic age-dependent neurodegenerative diseases. Similarly, to age-dependent dementias and sporadic late onset Alzheimer’s disease (LOAD) ( Bouhrara et al, 2018 ; Lin et al, 2020 ), CS is characterized by neuronal loss with severe demyelination, however with so far no detectable amyloid-beta accumulation and no hyperphosphorylated tau ( Woody et al, 1991 ; Han et al, 2023 ). Demyelination process implicates additional defects in oligodendrocytes of the central- and Schwann cells of the peripheral nervous system in CS disease progression.…”