Analyzing feed-forward loop relationship in aging phenotypes: physical activity and physical performance.

We present evidence of feed-forward loop relationships and positive association between physical activity and performance levels, which are components of frailty, using measures from 431 high functioning women initially aged 70-79 years followed over 7 visits. Physical activity levels were assessed using a questionnaire. Grip strength was measured using a handheld dynamometer and usual walking speed was measured over 4-m. The results suggest that a reduction in physical activity would not only degrade physical performance, but it would further reduce physical activity through declines in physical performance. As both physical activity and physical performance impact frailty, improvement of physical activity could help reduce frailty directly as well as indirectly via improved physical performance. Our findings support a priori hypothesis that feed-forward loops are present in the phenotype of frailty, which is due to dysregulated energetics. A methodologically broader implication is that we introduce modeling and analysis of feed-forward loop data here. The feed-forward loop, as we define it, is different from the concept of feedback loops used in biochemical systems. Generalizing our model of two-variable feed-forward loop, three, four or multivariable feed-forward loop can be applied to other biological systems.