Individuals differ from one another in nearly all attributes. These differences can have important demographic consequences, since variation accumulated over the lifetime of an individual can generate stochastic variation in the demographic processes that govern the dynamics of both natural and human populations. Most demographic approaches have traditionally focused on accounting for systematic sources of demographic variation (e.g., genetics, diet), yet the largest fraction of individual variation for most traits tends to reside in the "unexplained" category. What are the demographic consequences of this "unexplained" individual variation and is it possible to understand the underlying biological basis of what would otherwise appear to be random noise? Addressing these questions requires progress in two areas. First, we need precise estimates of the demographic trajectories of numerous genetically identical individuals so that the entire distribution individual outcomes can be characterized. Second, we need a statistical framework that allows for the accumulation of individual differences to be attributed to the inherent properties-the stochastic kernel-of that individual. The model nematode Caenorhabditis elegans is especially amenable to addressing these problems because it has become a central player in understanding the genetic and physiological bases of stress response and aging and because it can be used to generated large numbers of genetically identical individuals for demographic analysis. Here, we propose: (1) to develop new empirical and statistical approaches for the precise characterization of individual demographic trajectories, and (2) to test the stochastic dynamics model of life history variation using microfluidics to provide precisely controlled environmental perturbations in food availability and rearing temperature. We will accomplish these aims by manufacturing novel microfluidic systems that provide precise, automated characterization of the reproductive dynamics of many hundreds of individuals. A novel framework based on stochastic demography will then be used to analyze the data in order to estimate individual stochastic kernels for natural isolates and longevity-related mutants reared under conditions of dietary restriction and temperature variation. This exploratory/developmental project provides the basis for creating new approaches for understanding individual variation, which can be further expanded to help rigorously address some of the most difficult and longstanding questions in biodemography.

Public Health Relevance

The life that each individual leads is unique and is in large part determined by the experiences that they have and the conditions in which they live. Yet the individual consequences of these experiences are determined by the specific biological features of that individual. Understanding why individuals differ from one another is fundamental to understanding the reasons why there is variation in the incidence of disease and the onset of aging and whether this variation can ultimately be controlled to increase the likelihood that individuals will lead healthy lives.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG043988-02
Application #
8550761
Study Section
Special Emphasis Panel (ZRG1-PSE-H (59))
Program Officer
Finkelstein, David B
Project Start
2012-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$135,733
Indirect Cost
$41,233
Name
University of Oregon
Department
Type
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403