UCSF Researchers Identify Gene Family, Mutation Tied to Longevity
Researchers at the University of California, San Francisco, have identified around 200 genes and other biological systems that are believed to double the life span of C. elegans.
The researchers found that a single “life-extending mutation” in the daf-2 gene exerts its influence through antimicrobial and metabolic genes, through genes controlling the cellular stress response, and by dampening the activity of specific life-shortening genes.
Using RNA-interference technology, Kenyon’s team partially disabled one gene at a time, either in daf-2 mutants or in wild-type worms, and discovered that “no single gene by itself” determines lifespan. Of the “key genes” each can increase lifespan by between 10 and 30 percent. “But when daf-2 engages the whole army of genes, they can produce huge changes in lifespan,” the researchers report.
“This study tells us that there many genes that affect lifespan, each on its own having only a small effect,” Cynthia Kenyon, professor of biochemistry at UCSF and senior study author, said in a statement last week. “The beauty of the daf-2 gene is that it can bring all of these genes together into a common regulatory circuit. This allows it to produce these enormous effects on lifespan.”
A decade ago, Kenyon’s team discovered that a single mutation in the daf-2 gene — which encodes a hormone receptor similar to the human receptors for the hormones insulin and IGF-1 — doubled the worms’ lifespan. The team has since shown that the same or related hormone pathways affect lifespan in Drosophila and in mice, and “therefore are likely to control lifespan in humans as well.” Kenyon’s lab found that daf-2 affects lifespan through a second gene, daf-16, which controls the expression of other genes.
However, the researchers were soon left with important questions, namely: “What are the genes that daf-16 regulates?” The new research, published in the current issue of Nature, shows that “several key systems” are involved. They learned that “many” of the genes that affect lifespan code for antioxidant proteins, while others code for chaperone proteins that help repair or degrade damaged proteins. This is especially interesting, Kenyon said, because “many diseases of aging involve oxidative damage or protein aggregation.”
“The marvelous thing about this new study is that it provides an explanation not only for the remarkable longevity of these animals, but also for their ability to stay healthy so long,” Kenyon said. “They just turn up the expression of many, many different genes, each of which helps out in its own way.
“The consequences are stunning, and if we can figure out a way to copy these effects in humans, we might all be able to live very healthy long lives,” she added.
CSHL Launches Web Site for HapMap Data
Cold Spring Harbor Laboratories has made live its Haplotype Map Project Data Coordinating Center. The site, whose launch is two weeks ahead of schedule [see SNPtech Reporter, June 13, 2003], “currently serves as a download center” for the HapMap project and offers “public data downloads and some documentation, as well as private collaboration downloads/upload and other related project services,” according to CSHL.
As of June 24, the site, which can be found here, http://hapmap.cshl.org/, contains genotype and minor allele frequencies for approximately 60,000 SNPs and assay information released for download.
Lincoln Stein, the CSHL bioinformaticist who will oversee the site, said it will contain allele frequencies and individual genotypes from each of the HapMap labs. He said the consortium will pay for the site.