Dynamic models for the study of frailty.

Frailty can be viewed as resulting from the degradation of multiple interacting physiologic systems that are normally responsible for healthy adaptation to the daily demands of life. Mathematical models that can quantify alterations in the dynamics of physiologic systems and their interactions may help characterize the syndrome of frailty and enable investigators to test interventions to prevent its onset. One theoretical mathematical model reported by Varadhan et al. in this issue of the Journal represents one type of regulatory process that may become altered in frail individuals-the stimulus-response mechanism [Varadhan, R., Seplaki, C.S., Xue, Q.L., Bandeen-Roche, K., Fried, L.P. Stimulus-response paradigm for characterizing the loss of resilience in homeostatic regulation associated with frailty. Mech. Ageing Dev., this issue]. This model focuses on the timing of recovery from a single stimulus, rather than the full array of responses that might be altered in a complex dynamical system. Therefore, alternative models are needed to describe the wide variety of behaviors of physiologic systems over time and how they change with the onset of frailty. One such model, based on a simple signaling network composed of a lattice of nodes and the bi-directional connections between them, can reproduce the complex, fractal-like nature of healthy physiological processes. This model can be used to demonstrate how the degradation of signaling pathways within a physiologic system can result in the loss of complex dynamics that characterizes frailty.