Signs of aging: Scientists evaluate genes associated with longevity

Apr 18, 2005

Scientists at the BC Cancer Agency's Genome Sciences Centre in Vancouver, British Columbia, Canada, and at the University of Missouri-Columbia have collaborated on a detailed study to elucidate gene-expression patterns implicated in the aging process. Their results appear online today in the journal Genome Research.

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 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.

Source: Cold Spring Harbor Laboratory

Explore further: Radar search to find lost Aboriginal burial site

add to favorites email to friend print save as pdf

Related Stories

Radar search to find lost Aboriginal burial site

1 hour ago

Scientists said Tuesday they hope that radar technology will help them find a century-old Aboriginal burial ground on an Australian island, bringing some closure to the local indigenous population.

New planthopper species found in southern Spain

3 hours ago

Not much is known about the the genus of planthopper known as Conosimus, which now includes six species after a new one was recently discovered in the southern part of the Iberian Peninsula in the Spanish ...

Ex-Qualcomm exec pleads guilty to insider trading

11 hours ago

A former high-ranking executive of US computer chip giant Qualcomm pleaded guilty Monday to insider trading charges, including trades on a 2011 deal for Atheros Communications, officials said.

Recommended for you

P90X? Why consumers choose high-effort products

12 hours ago

Stuck in traffic? On hold for what seems like an eternity? Consumers often face situations that undermine their feelings of control. According to a new study in the Journal of Consumer Research, when a person's sense of con ...

Overdoing it: Multiple perspectives confuse consumers

12 hours ago

Television commercials for luxury vehicles pack a lot in their 30-second running times: the camera offers quick shots of the soft leather upholstery, the shiny colors, the state-of-the-art entertainment system, ...

User comments : 0