Forster M J, Lal H
Department of Pharmacology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Biomed Environ Sci. 1991 Jun;4(1-2):144-65.
Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important "neurobehavioral" markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.
由于中枢神经系统（CNS）功能对生产能力和生活质量至关重要，这些功能的生物标志物将在评估针对衰老过程的干预措施的成功与否中发挥关键作用。中枢神经系统生物标志物对于预测其他系统以及整个生物体的衰老也可能有用。与年龄相关的行为变化是中枢神经系统衰老的产物，在人类功能能力方面具有内容效度和预测效度，因此可能代表功能衰老的重要“神经行为”标志物。本文讨论了一些目前被视为小鼠衰老神经行为生物标志物的行为范式，以及用于评估其效度的实验方法。作者实验室进行的使用饮食限制和基因比较来评估神经行为生物标志物效度的研究揭示了几个方法学问题，并描述和讨论了这些陷阱的假设性和实证性例子。尽管存在这些问题，但得出的结论是，使用基因比较和饮食限制的效度评估方法可以成功实施，并最终应能鉴定出有效的、有用的衰老神经行为生物标志物。
