Drugs that mimic the effect of this genetic variation by lowering levels of CETP are already being tested as potential therapies for preventing heart disease. CETP inhibitors have been highly anticipated by cardiologists because they can raise the level of HDL cholesterol; current cholesterol drugs only lower the level of “bad” LDL cholesterol. However, Pfizer recently halted trials of its CETP inhibitor torcetrapib after the drug raised death rates in patients, which has prompted concerns that similar drugs will also fail.
Although the safety of CETP inhibitors is in question, Barzilai believes that companies developing the drugs should be looking at how they affect the brain as well as the heart. He believes that lowering CETP may not only help preserve healthy brain function but might also help prevent mental decline from Alzheimer’s disease.
The study, published this week in Neurology, is part of an ongoing effort to learn why some people who live long lives do so in better health than others do. “Most people study the genetics of disease, not the genetics of successful aging,” says Richard Lipton, study coauthor and head of the Einstein Aging Study. Researchers believe that examining the genes of long-lived people can offer scientists a guide for creating drugs that mimic the effects of their age-defying genes. Lipton says that the gene variation may help protect people from diseases of the brain, but that “there may also be a separate health-promotion effect distinct from the disease-prevention effect.”
Thomas Perls, a physician who leads the New England Centenarian Study at Boston University Medical Center, says that this latest finding “points to the utility of studying these extremely old individuals.” Researchers can take advantage of a phenomenon called “demographic selection” by focusing on people who survive when their peers have died out. “The older you get, the healthier you’ve been,” Perls explains.
But Perls says that although the current finding is promising, this gene variation, like other genetic variations that have been linked to longevity, has relatively modest effects. “As with all the other genes that groups including ours have discovered, it’s not a blockbuster. It’s not like we have found ‘the gene’ ” that controls aging. Perls says that longevity is probably highly complex, and living an exceptionally long life a long life may require a rare combination of different factors.