Characterization of physiological systems: biomarkers and statistical methods to measure changes in physiology across time and species

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Biologists have long sought to explain variation in animal life history traits (lifespan, reproductive rate, development rate) as a result of environment, and more recently to explain how natural selection works through physiology to affect life histories. However, the basic predictions have not been well supported: although life history traits often correlate with physiological markers such as hormones, immune function, and oxidative stress, these correlations vary in unpredictable ways across time and species. At the same time, aging scientists still have no convincing theory to explain the underlying physiological mechanisms of aging. Recently, I have proposed a new theory of physiology, aging, and evolution that explains these questions. Many aspects of physiology are linked in complex regulatory networks. Over time, the regulatory system can break down, resulting aging. These physiological systems will have properties such as evolvability and stability over time (e.g. resulting in longer lifespan) that will be determined by their structure and not be evident from their components alone. Here, I propose a research program to begin understanding these physiological systems from an ecological, evolutionary, and statistical perspective. Working under the hypothesis that directly measurable aspects of physiology are imperfect proxies for underlying processes, I will use sophisticated statistical tools such as PCA, SEM, and Bayesian multi-level models to identify and characterize these processes, establish their effects on each other over time, and measure how all of this varies at different time scales and across species. I will work on three systems to represent three timescales and levels of analysis: Tree Swallows will be used to measure changes in physiology over a short-term stress response, Bighorn Sheep will be used to measure changes over seasons and years, and an existing physiological database on 100+ bird species will be used to characterize changes over evolutionary time. The results are expected to establish new paradigms for (a) how ecologists study physiology, (b) how natural selection affects physiology and aging, and (c) the physiological processes underlying aging and chronic disease.