Longevity's secrets sought in DNA of 100-year-olds

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In this Tuesday, Oct. 18, 2011 photo, Marie Eberhardt helps her husband George Eberhardt, 107, of Chester, NJ. after they both got their annual flu shot in Mendham, N.J. George Eberhardt turned 107 in September 2011, and scientists would love to know how he and other older folks like him make it that far. So he's going to hand over some of his DNA. He is taking part in one of two projects announced in October 2011 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. (AP Photo/Mel Evans) In this Tuesday, Oct. 18, 2011 photo, Marie Eberhardt helps her husband George Eberhardt, 107, of Chester, NJ. after they both got their annual flu shot in Mendham, N.J. George Eberhardt turned 107 in September 2011, and scientists would love to know how he and other older folks like him make it that far. So he's going to hand over some of his DNA. He is taking part in one of two projects announced in October 2011 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. (AP Photo/Mel Evans) This Tuesday, Oct. 18, 2011 photo shows George Eberhardt, 107, of Chester, NJ. after being given his annual flu shot in Mendham, N.J. Eberhardt turned 107 in September 2011, and scientists would love to know how he and other older folks like him make it that far. So he's going to hand over some of his DNA. He is taking part in one of two projects announced in October 2011 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. (AP Photo/Mel Evans)eval("var currentItemd57851005a80479aaeeb90a12c70b9ff = 1;");eval("var nextd57851005a80479aaeeb90a12c70b9ff = 0;");eval("var previousd57851005a80479aaeeb90a12c70b9ff = 0;"); NEW YORK (AP) — 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," says Dr. Thomas Perls, a geriatrics expert at Boston University.

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, and it's the second sequencing project involving the elderly to be announced this month.

Genome pioneer J. Craig Venter says the centenarian project is just a first step in revealing the genetic secrets of a long and healthy life.

"We need 10,000 genomes, not 100, to start to understand the link between genetics, disease and wellness," said Venter, who is co-chairing the X Prize contest.

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.

But scientists believe there's more to it, and they want to use genome sequencing to investigate. Dr. Richard Cawthon of the University of Utah, who is seeking longevity genes by other means, says it may turn up genetic features that protect against multiple diseases or that slow the process of aging in general.

Protective features of a centenarian's DNA can even overcome less-than-ideal lifestyles, says Dr. 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.

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, says Dr. 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.

"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."

___

Online:

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

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

___

Malcolm Ritter can be followed at http://twitter.com/MalcolmRitter

Associated Press

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How the Brain Chooses: Secrets From Parkinson's Disease

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How do you make a tough choice? For most people, the answer is to pause and deliberate, as the brain puts the brakes on its initial impulses. Deep brain stimulation (DBS) used to treat Parkinson's disease, however, can interfere with this braking action, according to new research that is starting to reveal the anatomy of choice.

Parkinson's disease, which affects at least half a million Americans, is a progressive neurological disorder that is characterized by tremors and difficulty initiating and controlling movement, and can lead to dementia. Deep brain stimulation — which uses a device implanted in the brain like a pacemaker — can reduce symptoms when drug treatments fail.

DBS affects a part of the brain called the subthalamic nucleus (STN), which in turn affects multiple systems, according to Michael Frank, professor of cognitive, linguistic and psychological sciences at Brown University. During decision-making, it inhibits impulsive urges originating in a brain region known as the striatum. This allows a "pause," during which slower deliberation can take place in an area called the medial prefrontal cortex (mPFC).

The STN also affects movement in Parkinson's patients. "If the STN is really active, people have a hard time initiating movement," Frank says, which helps explain why people with Parkinson's may suffer from physical immobility or undirected shaking or become trapped in this "pause."

Consequently, DBS is used to regulate STN activity to ease movement. If it overshoots, however, it may allow impulses from the striatum to slip past the mPFC. That can sometimes lead to impulsive, unwise decision-making — and an increased risk of addictive disorders like gambling problems.

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(Interestingly, the specific activity of the STN may also explain why Parkinson's patients experience tremors: these occur at the same frequency as the activity seen in this brain region. The computer model used in the study predicts that tremor might increase in frequency during decision conflicts as STN activity rises.)

To figure all these connections out, Frank and his team recruited 65 healthy participants and 14 people with Parkinson's being treated with DBS for the study. The volunteers were given a decision-making task on a computer in which they had to choose between pictures that they had learned to associate with different levels of reward.

When the choice was difficult — for example, when faced with two pictures whose values were nearly equal — mPFC activity increased in all participants. Both healthy participants and people with Parkinson's, who had their DBS turned off, took longer to make up their minds.

But when DBS was activated in Parkinson's patients, they made decisions quickly and impulsively — even though mPFC activity was still seen. The mPFC wanted to deliberate, but deep-brain stimulation prevented the STN from hitting the brakes on impulsive urges.

While impulsivity as a side effect of DBS can currently be managed when it occurs, Frank's research suggests that tweaking the stimulation to better allow communication between the STN and the mPFC could improve treatment.

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Activity in the STN may also be involved in the "paradox of choice," in which people become overwhelmed by having too many options. In one famous study of this phenomenon, researchers found that people were easily able to choose between four types of jam in a supermarket, but when faced with 12 different options, they couldn't bring themselves to decide at all.

"We think this mechanism is at play, where too much conflict [puts] a brake on the decision-making system. The brain did not evolve in a world where we are given a myriad of options in a supermarket," Frank says. "The sort of decision paralysis observed in that case might be a byproduct of a the healthy tendency to pause in the face of conflict."

This kind of mental incapacitation may also play a role in various psychiatric disorders. For example, people with depression often feel "stuck" because their inability to experience pleasure makes it impossible for them, when faced with any kind of choice, to judge one option as better than the other.

In people with addiction, the reward systems involving the striatum are trained to respond as people repeatedly experience pleasure by taking a drug. To quit successfully, the STN needs to prevent the striatum from initiating the behaviors needed to get high. "Any way in which that circuit can be trained up or enhanced could potentially be helpful for people with addictions," says Frank.

The study was published in Nature Neuroscience.

MORE: Man Claims Parkinson's Drug Turned Him Into a Gay Sex Addict

Maia Szalavitz is a health writer at TIME.com. Find her on Twitter at @maiasz. You can also continue the discussion on TIME Healthland's Facebook page and on Twitter at @TIMEHealthland.

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