Systems Genetics Approach to the Biology of Aging

The aging of the population is having a tremendous societal impact. The main goal of AgingX is to contribute to this aging challenge by aiming to better understand the biology of aging and to identify strategies to increase healthspan.

Disturbances of cellular metabolism, often linked to mitochondrial dysfunction, critically influence whole body metabolism and are, as such, prime determinants for lifespan and healthspan. Although mechanistic studies revealing the importance of mitochondrial activity have been highly informative on a cellular level, we now need new and integrative systems genetics resources to efficiently study the complex metabolic and mitochondrial networks that are linked to aging. This is necessary because aging is a truly multifactorial process, mediated by gene networks which integrate genetic and environmental cues.

Solid foundation to understand aging

We plan to study aging in a context that aims to mimic the genetic, molecular, and environmental complexities observed in natural populations. The specific goals of this project are:

• The measurement of gene-by-environment effects on lifespan and healthspan phenotypes by studying the variation in aging in Drosophila melanogaster (fruit fly) and mouse genetic reference panels subjected to a normal or high-fat diet;
•  The investigation of gene-by-environment effects on molecular networks, metabolic biomarkers, and mitochondrial function;
• The integration of data and the performance of cross-species modeling of gene and network effects;
• The validation of implicated genes and networks in C. elegans and Drosophila and the translation of the findings to humans.

We believe that a clear model of the transfer of biological knowledge – from gene function to networks and phenotypes – across species constitutes a critical component of future systems biology and genetics. For this reason, these combined, cross-species efforts should provide a solid foundation to increase our understanding of the genetics and biology of aging, which may ultimately support the development of strategies to improve human healthspan.

Updated June 2014