Research Seminar: Transcriptomic signature of longevity in C. elegans

Dr. Collin Ewald, ETH Zurich, Institute for Translational Medicine, Department of Health Sciences and Technology

Tuesday 27th November, 12.00 noon, Ingram Lecture Theatre

Aging is the progressive decline of physiological integrity and function of an organism over time ultimately leading to the onset of age-dependent diseases. Longevity interventions, such as caloric restriction and reduced insulin/IGF-1 signaling, slow down the aging process. The nematode Caenorhabditis elegans is a key model system to study the role of aging and longevity. In the current literature, there is an abundance of studies describing gene expression changes associated with longevity. However, we currently lack an overall conceptual understanding of how the individual longevity interventions are related. Do longevity interventions share downstream targets or act via distinct mechanisms and are there genes, which consistently accompany longevity?

To answer these questions, we re-analyzed published longevity expression profiles (190 arrays, 130 sequencing runs) to directly compare longevity regulation across studies. We extracted and combined the gene expression changes caused by all known longevity interventions in C. elegans to identify the underlying gene expression signatures that might promote healthy aging. By re-analyzing the published datasets with a common pipeline, we are able to correct for variations arising from different laboratory conditions or used strains to extract the changes that are more longevity-specific. The majority of genes we found to be differentially expressed across longevity interventions in C. elegans are downregulated during physiological aging. Intriguingly, longevity interventions display a large overlap in their targeted pathways indicating a shared mode of action. To expand the view offered by annotated pathways, we performed a GO term enrichment and identified the extracellular matrix genes as a key target enriched in both aging and longevity. Our comparative approach revealed a more robust network of gene expression changes shared by longevity intervention. These findings can be directly used to generate hypothesis to reveal novel mechanisms that promote healthy aging.