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Complexity, robustness, frailty, hierarchy

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Systems Biology and Aging

 

Robustness, complexity, frailty and hierarchy

Overall question: What are the mechanisms underlying the degradation of integrated networks associated with aging, how do we quantify this degradation with notions like complexity, and how do these mechanisms impair adaptation and ultimately survival?

Drilling down:

1) How can we predict vulnerability to functional decline and early mortality? (Conversely, How can we predict robustness?)

2) What are the structural and functional changes (genetic, epigenetic, metabolic, physiologic, and their interactions) that predict the ability (or lack of ability) to respond to a given stress as we age?

3) What is the dependent variable that captures the ability to adapt to stress (or vulnerability)? This should be a measure of functional impairment – an integrated readout of a system; e.g. VO2max, gait speed, immunity. But we need to define adaptation using a stress test – e.g., flu immunization, exercise, temperature change, etc.

4) What are the methods of systems biology that allow us to address these questions?

a) We need markers of the output of each component.
b) We need to interfere with each component of contributing systems to see how it affects the functional outcome. E.g. pharmacologic interventions, RNAi, knock-outs. We can then model the networks contributing to an outcome.
c) We need to do the interventions at different ages to determine the relative importance of network components and their hierarchy.