Behavioral and neuronal biomarkers of aging and disease: Integration with physical performance and function

Aging is a heterogeneous process characterized by marked variability in biological, cognitive, and functional trajectories among individuals of the same chronological age. Consequently, there is greater interest in biomarkers capable of identifying early deviations from healthy aging and predicting adverse outcomes. This review provides an updated overview of neuronal and behavioral biomarkers associated with aging and disease and discusses their integration with physical performance and functional outcomes in older adults. Neuronal biomarkers, including neuroimaging, blood-based, and neurovascular markers, capture key biological processes such as neurodegeneration, neuroinflammation, vascular dysfunction, and impaired resilience. Behavioral biomarkers, including gait, mobility, dual-task performance, balance, physical activity, sleep, and digital phenotyping, reflect the functional expression of these underlying biological changes. Evidence suggests that alterations in these biomarkers may precede cognitive decline, frailty, disability, and loss of independence by several years. Integrating neuronal and behavioral biomarkers with measures of physical performance provides a comprehensive framework for identifying individuals at increased risk of adverse aging trajectories and may support precision geroscience approaches aimed at preserving intrinsic capacity, functional ability, and healthy aging. Future research should focus on validating multimodal biomarker models and their application in clinical and population settings.