Researchers have discovered a region on chromosome 4 that appears to contain one or more genes that enable humans to survive to extremely old ages. The results, if they hold up, would offer new insights into the process of aging--and might provide clues about how to slow down the process. "If it turns out to be true, it's really important for gerontology," says George Martin, a pathologist at the University of Washington, Seattle.
Extreme longevity clusters in some families, and researchers have fiercely debated for decades whether it stems from purely environmental factors or is partly genetic. So far, several groups have identified human genes and regions of mitochondrial DNA that might contribute a bit to longevity, for instance by protecting against cardiovascular disease and Alzheimer's. In addition, single genes in lab animals can dramatically lengthen life-span (Science, 6 April, p. 41). But until now, no one had undertaken a genome-wide scan to look for genetic regions that confer exceptional life-span in humans.
Harvard geriatrician Thomas Perls, molecular geneticist Louis Kunkel of Children's Hospital in Boston, and their colleagues studied 137 sets of extremely old siblings, each including one person who was at least 98 years old and any brothers or sisters who were at least 91 and 95, respectively. The team searched for stretches of DNA shared by the siblings and present at a frequency higher than expected by chance. A lengthy tract on chromosome 4 fit the bill, the researchers report in the 28 August Proceedings of the National Academy of Sciences. The region may contain one or several "genetic booster rockets," as Perls describes them, genes that slow aging and decrease susceptibility to all age-related diseases.
"If [the result] holds up in future studies, it suggests that there is a genetic component--and that a single gene contributes a great deal," says Leonid Kruglyak, a geneticist at the Fred Hutchinson Cancer Research Center in Seattle. Experts caution, however, that that the Harvard group's data lie at the edge of statistical significance. "The evidence in this analysis is too flimsy to warrant getting very excited," says Thomas Kirkwood, a gerontologist at the University of Newcastle in the United Kingdom. Not only is the statistical significance low, he says, "but the statistical assumptions used to generate it have not been verified."
To address that problem, the team is scouting for more long-lived siblings so they can repeat the study. Meanwhile, they've started a company, Centagenetix, that is trying to narrow down the span of interesting DNA, which contains hundreds of genes.