Researchers at the University of Arkansas for Medical Sciences (UAMS) have reported a 10-fold life extension in the complex animal C. elegans, tiny worms that live in the soil.
Reported in the February 2008 issue of the journal Aging Cell, the discovery was made by a team of researchers headed by Robert Shmookler Reis, professor in the UAMS Departments of Geriatrics, Biochemistry/Molecular Biology and Pharmacology/Toxicology and research scientist at the Central Arkansas Veterans Healthcare System.
C. elegans are barely visible to the eye but are helping scientists unravel the causes of aging and understand what determines life span, Reis said. During the past 15 years, more than 80 mutations have been found that extend life in C. elegans, including components of a worm signaling pathway (a set of genes that responds to signals from the environment or within the worm) that is equally related to insulin signaling and insulin-like growth factor (IGF-1) signaling in mammals.
Insulin alerts cells that there are nutrients in the blood ready to be used, whereas IGF-1 stimulates growth. Interfering with insulin signaling results in insulin resistance, a condition that can develop into diabetes. Interfering with IGF-1 signaling produces effects in mammals more akin to those seen in long-lived worms. Mice mildly deficient in IGF-1 receptor are long-lived and appear healthy, Reis said, adding that the longest-lived humans tend to have diminished IGF-1 signaling as well.
“These observations hint that processes discovered in the worm also are relevant to aging in humans,” Reis said, “but we shouldn’t expect exact parallels.”
Reis’ team discovered that a mutant in the insulin/ IGF-1 pathway of C. elegans slows development but ultimately produces adults he described as “super survivors,” able to resist levels of toxic chemicals that would kill an ordinary worm. Although the adult lifespan of C. elegans is normally only two to three weeks, half of the mutant worms were still alive after six months, with some surviving to nine months.
“We knew we had found something amazing,” said Srinivas Ayyadevara, Ph.D., research assistant professor in the UAMS Donald W. Reynolds Institute on Aging. “These worms continue to look and act like normal worms of one-tenth their age.”
Reis cautioned that the discovery does not mean that an 800-year human life span is just around the corner. “Worms have a short lifespan to begin with, so it seems to be relatively easy to prod them to live longer. Other mutations, which extend the life of C. elegans up to 2.5-fold, give a much smaller benefit in mice,” he said.
“The important thing is that we now have a pretty good idea of what we should try in order to increase mouse lifespan by 50 to 100 percent. We are on a path now that might lead to similar gains from a single genetic change or drug given to mice, and eventually to a treatment that could benefit humans.”
To view the article, visit http://www.uams.edu/update/news/aging_cell.pdf.
