Scripps study focuses on genetic links to health

By Gina McGalliard

Most genetic medical research looks at disease or illness, but Dr. Eric J. Topal hopes to reverse that trend. Instead of studying genes that cause illness, Topal studies genes that keep people healthy late into life.

Topal directs the Wellderly study at Scripps. Participants are healthy individuals age 80 and beyond who are free of chronic disease and not on any medications except those common to elderly patients. The study will analyze DNA to find out what the genetic mechanisms are that keep people healthy over the course of a lifetime.

“So many groups around the world have studied longevity, but our study is very unique because it focuses on health span rather than life span,” said Dr. Topal.

The study seeks to find specific genes that protect people from disease or illness, also known as protective alleles. The function of these genes is that they cancel out or neutralize other genes that may put someone at a higher risk for conditions such as heart disease or breast cancer. Therefore, according to Dr. Topal, people who have lived a long life in relatively good health are not necessarily lacking in “bad” genes, but simply have what he calls “modifier” genes.

“They don’t necessarily have good genes, they have good modifier genes,” said Dr. Topal.

Some may be surprised to find out that the study’s participants have not necessarily led a healthy lifestyle. “We had a 97-year-old who still smokes two packs of cigarettes a day,” said Dr. Topal. “It’s quite heterogeneous; not as healthy as you would think.” He also said that this makes the participants the “ideal population” in which to study modifier genes, because they often have health-risk factors such as smoking, poor diet and lack of exercise, yet they are still in good health at a late age.

Participant Forrest Adams, who is a medical doctor himself, said that he has not always led the healthiest lifestyle. “I’ve always told people, ‘Don’t admire what a wonderful way I take care of myself,’ ” he said. Despite this, he is 88 years old and has always been in relatively good health. “I’ve been relatively free of disease,” he said.

Dr. Adams also said longevity runs in his family. He happens to be a direct descendant of Presidents John Adams and John Quincy Adams, who both lived to an old age.

“All my immediate relatives all lived to be in their nineties. And I’m 88,” he said. As a medical doctor, he also thinks it is highly likely that there is a gene that protects him from disease. Not only is he in good health at an advanced age, but as a practicing physician, he was exposed to much contagious disease, first to victims of polio and later to patients of infectious disease.

Dr. Adams also said that the study’s focus on health was an incentive for him to participate. “That’s why when I heard about this study I quickly joined in. It’s the emphasis on health that intrigued me about this particular study.”

According to Dr. Topal, the crux of the research is finding out why some individuals who have either high-risk genes and/or an unhealthy lifestyle are still able to lead a long life in good health. “It isn’t only lifestyle that is the story here,” he said. Although he does not deny that lifestyle can have a great effect on health, he said that DNA is also a “powerful factor.”

Because healthy people are not likely to visit the hospital, the study has had to make an effort to find qualified participants. As a result, Scripps has reached out into the community in order to find participants, and publicity for the study has yielded good results. Dr. Topal said that he often finds that people are proud of having reached an advanced age in good health, and therefore are enthusiastic about participating.

Another reason Dr. Topal feels optimistic about the study is that genetic research has undergone a period of rapid growth in the last six months. Since April of this year, he said that there are as many as 30 different diseases that have been found to have “genetic underpinnings.” He feels that the Wellderly study, which focuses on health-related modifier genes, will allow people to have a more complete picture of their genetic makeup. For instance, an individual could not only find out that they carried the gene for a higher risk of breast cancer, but also that they had a modifier gene that canceled out the risk that rendered it almost at zero.

Dr. Topal also hopes that his research and other genetic-based research like it will help revolutionize medicine, because identification of a modifier gene will change the way scientists look at genetics.

“These are the things that are shaping the future of medicine,” said Dr. Topal.

If you are interested in participating in the study and think you may qualify, call 1-800-Scripps.