Department of Pharmacology, University of Cambridge, Tennis Ct Rd, Cambridge, CB2 1PD, UK.
Aging Cell. 2023 May;22(5):e13830. doi: 10.1111/acel.13830. Epub 2023 Apr 3.
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.
衰老是迟发性神经退行性疾病的最大风险因素。在散发性 tau 病领域中，在实验动物中模拟生物衰老过程是寻找致病 tau 的分子起源和开发潜在治疗干预措施的基础。尽管先前的转 tau 模型研究为研究 tau 突变和过表达如何引发 tau 病变提供了有价值的经验教训，但衰老导致异常 tau 积累的潜在机制仍知之甚少。与人类早衰综合征相关的突变被认为能够在动物模型中模拟衰老环境。在这里，我们总结了最近使用携带与人类早衰综合征相关的突变、与人类早衰综合征无关的遗传元件、具有异常自然寿命或对与衰老相关的疾病具有显著抗性的动物模型来模拟与 tau 病相关的衰老的尝试。
