Signs of aging: Scientists evaluate genes associated with longevity

April 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

Related Stories

Recommended for you

Climate scientist hits out at IPCC projections

October 13, 2015

As a new chairman is appointed to the Intergovernmental Panel on climate Change (IPCC) a University of Manchester climate expert has said headline projections from the organisation about future warming are 'wildly over optimistic.'

The culinary habits of the Stonehenge builders

October 13, 2015

A team of archaeologists at the University of York have revealed new insights into cuisine choices and eating habits at Durrington Walls – a Late Neolithic monument and settlement site thought to be the residence for the ...

A particle purely made of nuclear force

October 13, 2015

Scientists at TU Wien (Vienna) have calculated that the meson f0(1710) could be a very special particle – the long-sought-after glueball, a particle composed of pure force.

Dead comets and near-earth encounters

October 13, 2015

Near Earth Objects (NEOs) are asteroids or comets whose orbits sometimes bring them close to the Earth, thereby posing a potentially threat. The asteroid that struck Chelyabinsk last year was an NEO about 40 meters in diameter. ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.