Scientists studying complete genetic profiles of centenarians to find the secret of longevity

By Dr. Ananya Mandal, MDOct 27 2011

Scientists have announced Wednesday that they would 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. They speculate that 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 people stay disease-free longer.

Thomas Perls, a geriatrics expert at Boston University said reaching 105 is “very hard… without some genetic advantages.” Dr. Richard Cawthon at the University of Utah is working on the same point examining more limited sequencing.

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.

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?”

Cawthon and his co-researchers — medical sociologist Ken Smith at the University of Utah's Huntsman Cancer Institute; Richard Kerber and Elizabeth O’Brien, both epidemiologists formerly at the University of Utah but now at the University of Louisville — are taking a different approach 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. “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, “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.”

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.”