Marcozzi Serena, Bigossi Giorgia, Giuliani Maria Elisa, Lai Giovanni, Bartozzi Beatrice, Balietti Marta, Casoli Tiziana, Orlando Fiorenza, Amoroso Andrea, Giacconi Robertina, Cardelli Maurizio, Piacenza Francesco, Lattanzio Fabrizia, Olivieri Fabiola, de Keizer Peter L J, d'Adda di Fagagna Fabrizio, Malavolta Marco
Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.
Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy.
Aging Cell. 2025 Jul;24(7):e70056. doi: 10.1111/acel.70056. Epub 2025 May 21.
Loss of cognitive function is a significant challenge in aging, and developing models to understand and target cognitive decline is crucial for the development of Geroscience-based interventions. Aged mice offer a valuable model as they share features of cognitive decline with humans. Despite numerous studies, knowledge of longitudinal age-related cognitive changes and cognitive frailty in naturally aging mice is limited, particularly in cohorts exceeding 30 months of age, where cognitive decline is more pronounced. Moreover, the impaired physical function of aged mice is known to affect latency-based strategies to measure cognitive performances. Here, we show a comprehensive longitudinal assessment using the Barnes Maze test in a large cohort of 424 aged (≥ 21 months) C57BL/6J mice. We introduced a new metric, the Cognitive Frailty Index (CoFI), which summarizes different age-associated Barnes Maze parameters into a unique function. CoFI strongly associates with advancing age and mortality, offering a reliable ability to discriminate long- and short-lived mice. We also established a CoFI cut-off and a physically adjusted CoFI, both of which can distinguish between physical and cognitive frailty. This is further supported by the enhanced predictive power when physical and cognitive frailty are combined to assess short-term mortality. Moreover, the computation method for CoFI is adaptable to various cognitive assessment tests, leveraging procedures akin to those used for calculating other frailty indices. In conclusion, through robust longitudinal tracking, CoFI has the potential to become an important ally in assessing the effectiveness of Geroscience-based interventions to counteract age-related cognitive impairment.
认知功能丧失是衰老过程中的一项重大挑战，开发用于理解和针对认知衰退的模型对于基于老年科学的干预措施的发展至关重要。老年小鼠提供了一个有价值的模型，因为它们与人类共享认知衰退的特征。尽管有大量研究，但对于自然衰老小鼠中与年龄相关的纵向认知变化和认知衰弱的了解仍然有限，特别是在超过30个月龄的队列中，那里认知衰退更为明显。此外，已知老年小鼠受损的身体功能会影响基于潜伏期的认知表现测量策略。在这里，我们展示了在424只年龄≥21个月的老年C57BL/6J小鼠的大型队列中使用巴恩斯迷宫测试进行的全面纵向评估。我们引入了一个新指标，即认知衰弱指数（CoFI），它将不同的与年龄相关的巴恩斯迷宫参数汇总为一个独特的函数。CoFI与年龄增长和死亡率密切相关，具有区分长寿和短寿小鼠的可靠能力。我们还建立了CoFI临界值和身体调整后的CoFI，两者都可以区分身体衰弱和认知衰弱。当将身体衰弱和认知衰弱结合起来评估短期死亡率时，预测能力增强进一步支持了这一点。此外，CoFI的计算方法适用于各种认知评估测试，利用类似于用于计算其他衰弱指数的程序。总之，通过强大的纵向跟踪，CoFI有可能成为评估基于老年科学的干预措施以对抗与年龄相关的认知障碍有效性的重要帮手。
