A substantial fraction of the variation in aging can be explained by genetics, but little is known about what these genetic factors are and how they modulate healthy aging. Much of our fundamental understanding of mechanisms that modulate aging, including insulin signaling and proteostasis pathways, come from the study of the model nematode Caenorhabditis elegans. Nearly all C. elegans aging studies use a single laboratory- adapted strain with little connection to natural variation. In this project we aim to establish C. elegans as a model for natural variation in aging. First we will develop a system for multi-modal automated healthspan assays based on a previously developed `WorMotel' microfabricated multi-well imaging platform. Second, we will carry out longitudinal assays on 16 genotypically diverged wild-isolate C. elegans strains to determine traits correlated with healthspan decline. Our results will set the stage for comprehensive mechanistic analysis of genes underlying natural variation in aging. The combination of high-throughput healthspan analysis and quantitative genetics methods will be particularly powerful for delineating genetic causes of a complex healthspan phenotype, providing the first mechanistic understanding of natural variation in metazoan aging.

Public Health Relevance

The study of model organisms such as the roundworm C. elegans is improving our understanding of how human aging occurs. Our research will develop automated tools for measuring the health of C. elegans and use them to discover genes responsible for aging rates in different wild strains of C. elegans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG053638-01A1
Application #
9317070
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Guo, Max
Project Start
2017-08-01
Project End
2019-05-31
Budget Start
2017-08-01
Budget End
2018-05-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104