expression. This 'hypo-metabolic' state, which involved major lipid, nucleic acid, protein, and energy pathways, became less pronounced with advanced age. "We speculate that the apparent metabolic repression in early and mid-life adults contributes substantially to the observed longevity of daf-2," says Dr. Julius Halaschek-Wiener, a researcher at the BC Cancer Agency's Genome Sciences Centre and first author on the study.

Another notable observation was that stress-response factors such as hsp, mtl-1, gst-1, and sip-1 were more abundantly expressed in the aging adult worms as compared to the early and mid-life adults. These genes were also differentially expressed between daf-2 mutants and controls, consistent with current theories that protection against cellular stress is associated with increased lifespan.

The researchers hope that their observations in C. elegans will contribute to our understanding of human aging. "Many processes involved in nematode aging may have fundamental and analogous roles in humans," Dr. Brooks-Wilson explains. "The human orthologs of some gene family members identified in this study have been associated with human age-related diseases."

SAGE involves the isolation of short gene-specific sequence tags and provides an unbiased and quantitative measurement of gene-expression differences. This study was the first to utilize SAGE to analyze aging-related gene-expression changes. It is expected that the large volume of SAGE data generated for this study will also be utilized to more fully annotate the C. elegans transcriptome, resulting in a refined estimate of gene number and organization in this species.

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Contact: Maria A. Smit
smit@cshl.edu
1-516-422-4013
Cold Spring Harbor Laboratory
17-Apr-2005

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