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Most scientists who study human longevity search for genes that determine who is most likely to make it to age 100. Researchers at the University of Miami are taking a different approach: They’re studying the genes that allow people to stay healthy into old age.

By focusing on Amish people who have lived to 80, the researchers hope to pinpoint the genes that promote “successful aging”—the ability to live without disease, depression, frailty, or loss of independence for longer than average. “We’re looking not just to predict how old you’ll get, but how well you’ll age,” says William K. Scott, professor of human genetics at the university’s school of medicine.

Scott and his colleagues think they may have found one such key to successful aging. On Friday they will present a paper showing that 15 percent of healthy Amish octogenarians have “haplogroup X,” a genetic pattern within the mitochondria, which are the regions of cells that generate energy and help guard against deterioration. Haplogroup X is generally found in only 2 percent of Europeans, from whom the Amish descended. In the University of Miami study, only 3 percent of the control group—Amish people who had made it to 80 but suffered from significant disease or disability—had the genetic variant. The paper will be featured during a session at the American Society of Human Genetics’ annual meeting in Washington, D.C.

Researchers who study aging have long suspected that mitochondria play a role in aging. Mitochondria are responsible for processing metabolized food particles into adenosine triphosphate, which fuels vital cellular processes. They’re also involved in cell growth and differentiation. But the ability of mitochondria to function properly seems to decline with age.

Understanding the reason for that decline—and the genes that might control it—has been challenging. Mitochondria have their own DNA, which is passed down from the mother only. This unique chromosome has variations, called haplogroups. Nine such haplogroups have been well characterized in people of European descent, Scott says. But only haplogroup X was found to be prevalent among healthy aged people in the University of Miami study.

Isolated communities have become popular laboratories for studying longevity. In addition to Scott’s team, which is working with Amish families in Indiana and Ohio, a group at the University of Maryland is researching aging in the Amish of Pennsylvania. And Michael H. Crawford, director of the University of Kansas’s laboratory of biological anthropology, has spent years studying Mennonites in the Midwest. “The advantage of working with a homogeneous population is, you’re reducing the variances that can be associated with the environment,” Crawford says. Mennonites and Amish “don’t drink, don’t smoke. Most do some sort of physical activity. They don’t sit around working on a computer all day.”

But there can be pitfalls to this approach. Crawford says it’s hard to parse whether environment and lifestyle play as much of a role in successful aging as genetics, especially when the control group comes from the same community as the experimental group. What’s more, he says, tight-knit communities may not have enough genetic diversity to allow scientists to find variations such as haplogroups.

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Tagged: Biomedicine, DNA, aging, longevity, genes

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