Led by Dr. Angela Brooks-Wilson, Senior Scientist at the BC Cancer Agency's Genome Sciences Centre, and Dr. Donald Riddle, Professor of Biology at the University of Missouri, the team prepared SAGE (serial analysis of gene expression) libraries from roundworms that contained a mutated form of the daf-2 gene, which is a principal lifespan-determining factor in C. elegans. Worms that lack fully functional daf-2 exhibit significantly extended lives, persisting approximately twice as long as their wild-type counterparts.
Daf-2 was first reported as a critical aging-associated gene in 1993, but since that time, scientists have identified dozens of additional genes that are crucial for longevity. "Aging is a complex process," explains Dr. Brooks-Wilson. "It is commonly believed that a variety of genes and metabolic pathways contribute to the deterioration of cells, tissues and organisms during aging."
In an effort to perform a comprehensive analysis of gerontology-related genes, the researchers compared gene-expression libraries obtained from daf-2 mutants to those obtained from controls at different ages. They predicted that genes exhibiting coordinated up- or down-regulation from early to late adulthood would be those most critical to the vital biological process of aging. In addition, they reasoned that some of the genes that were differentially expressed between daf-2 mutants and controls would also be associated with longevity.
Most strikingly, the scientists observed that during the early and mid-life adult stages of daf-2 mutants, genes associated with metabolic processes exhibited repressed
Contact: Maria A. Smit
Cold Spring Harbor Laboratory