Utah research helps unlock secrets in very old people's DNA

New York • George Eberhardt turned 107 last month, and scientists would love to know how he and other older folks like him made it that far. So he's going to hand over some of his DNA.

He's one of 100 centenarians taking part in a project announced Wednesday that will examine some of the oldest citizens with one of the newest scientific tools: whole-genome sequencing, the deciphering of a person's complete collection of DNA.

Scientists think DNA from very old healthy people could offer clues to how they lived so long. And that could one day lead to medicines to help the rest of us stay disease-free longer.

By the time you reach, say, 105, "it's very hard to get there without some genetic advantages," said Thomas Perls, a geriatrics expert at Boston University.

Dr. Richard Cawthon at the University of Utah is working on the same puzzle, examining more limited sequencing. But the goal is the same: Build evidence that a particular gene contributes to longevity, in order to protect against multiple diseases or slow the process of aging in general.

Perls is helping find centenarians for the Archon Genomics X Prize competition. The X Prize Foundation, best known for a spaceflight competition, is offering $10 million in prize money to researchers who decipher the complete DNA code from 100 people older than 100. The contest will be judged on accuracy, completeness and the speed and cost of sequencing.

The contest is a relaunch of an older competition with a new focus on centenarians. Earlier this month, Scripps Health of San Diego announced a different genome project involving the elderly. The Scripps Wellderly Study will receive the complete genomes of 1,000 people age 80 and older from a sequencing company.

A complete genome reveals not only genes but also other DNA that's responsible for regulating genes. It's "the full monty," showing DNA elements that are key for illness and health, said Eric Topol, who heads the Wellderly Study.

Participants in that study have an average age of 87 and range up to 108, and they've never had diabetes, heart disease or cancer, or any neurological disease.

"Why are these people Teflon-coated?" Topol asked. "Why don't they get disease?"

The ability to turn out lots of complete genomes is "the new-new thing" in trying to find out, he said.

Cawthon and his co-researchers — medical sociologist Ken Smith at the U.'s Huntsman Cancer Institute; Richard Kerber and Elizabeth O'Brien, both epidemiologists formerly at the U. but now at the University of Louisville — are taking a different tack to answer the question Topol raises.

Starting with the Utah Population Database, they searched for clusters of extremely long-lived family members with what the researchers call "excess sharing" in their DNA. For their purposes, extremely long-lived means people who lived well beyond standard life expectancies.

The researchers are looking at genetic linkages to define the boundaries of a region they can sequence that is less extensive than the whole genome, Cawthon said. The next step is to screen unrelated long-lived people for the same DNA variant. Since the DNA they are looking at comes from people of European descent, the control group would be the general European population who have been sequenced.

"We're looking for a DNA difference that may be causing the [longevity] trait," Cawthon said.

For all the major killing diseases, age is the biggest single risk factor. Medicines could be developed to mimic the best version of the longevity genes.

"There's been too much emphasis on disorders per se and not enough on the people who are exceptionally healthy," to learn from their genomes, Topol said. "Now we have the powerful tools to do that."

Cawthon said research dollars are better spent on aging research than on individual diseases."If you completely eliminated cancer, you would only increase average life expectancy by three years," he said. But slowing aging "attacks all the diseases at once."

Between age 30 and 90, the risk of dying doubles every eight years. "There must be some molecular correlative," he said.

People would still die, Cawthon said. But they would die of the causes that kill people in their 20s — unintentional injury, homicide, suicide, congenital illness, flu, pneumonia and other ailments not necessarily linked to old age.

Cawthon said co-researcher Smith says if people could keep their risk of dying constant with what it is in their 20s, women would live an average of 1,500 years, men an average 500 years. The difference would be due to multiple factors, including men's higher level of risk-taking and women's extra X chromosome.

The 107-year-old Eberhardt of Chester, N.J., played and taught tennis until he was 94. He said he's participating in the X Prize project because he's interested in science and technology. It's not clear his genes will reveal much. Nobody else in his extended family reached 100, and he thinks only a couple reached 90, he said in a telephone interview.

So why does he think he lived so long? He credits 70 years of marriage to his wife, Marie. She in turn cites his "intense interest in so many things" over a lifetime, from building radios as a child to pursuing a career in electronics research.

Protective features of a centenarian's DNA can even overcome less-than-ideal lifestyles, says Nir Barzilai of the Albert Einstein College of Medicine in New York. His own study of how centenarians live found that "as a group, they haven't done the right things."

Many in the group he studied were obese or overweight. Many were smokers, and few exercised or followed a vegetarian diet. His oldest participant, who died this month just short of her 110th birthday, smoked for 95 years.

"She had genes that protected her against the environment," Barzilai said. One of her sisters died at 102, and one of her brothers is 105 and still manages a hedge fund.

Genes that protect against the environment may also protect against disease and illness, Cawthon said. But they can't do all the work. People still have to safeguard their health. "We should not start to believe that genes are all that matter," he said. "But if you want to get to extreme age, you need good genes."

Tribune reporter Patty Henetz contributed to this report.

—

Online:

X Prize competition: http://genomics.xprize.org/

Wellderly Study: http://bit.ly/pHFHDj —

Studying healthy elders

Research at the University of Utah and two other studies announced this month are looking at genetic traits of long-lived people for possible medicines of the future that could guard against all major killing diseases.

X Prize competition > http://genomics.xprize.org/

Wellderly Study > http://bit.ly/pHFHDj