For Some, Long Life Is in the Genes
Genetic mutation may explain why some people become centenarians
TUESDAY, Oct. 14, 2003 (HealthDayNews) -- For eons, society has attributed long life to certain vague and mysterious "good genes."
Now researchers appear to have identified one of these genes -- or, more specifically, a genetic mutation that may let people live into their 90s and even past 100.
The gene in question governs a single amino acid in a protein that leads to the production of larger high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. HDL is often referred to as "good" cholesterol, and LDL has the moniker of "bad" cholesterol. Apparently, these larger molecules protect against many diseases of aging, including heart disease, stroke and diabetes.
"This is the first gene that was associated with longevity," says Dr. Nir Barzilai, lead author of a study appearing in the Oct. 15 issue of the Journal of the American Medical Association. "I think there will be more."
"We know that centenarians in many cases seem to miss getting the major diseases that kill a lot of other people at much younger ages," says Winifred K. Rossi, special assistant for planning at the National Institute on Aging, which helped fund the study. "The question is why are these people so good, and what are the protective factors that help them get away from those major diseases."
While almost all the people that Barzilai has studied had larger-size molecules, only 25 percent had the genetic mutation. "There are other genes that are probably doing the same thing," he says.
And research that has not yet been published indicates this mutation may also have an effect on cancer and on the brain.
For the current study, Barzilai and his colleagues examined and took blood samples from 213 Ashkenazi Jewish men and women and 216 of their children. The average age of the parents was 98 and almost half were over 100; the range was 95 to 107. The children had an average age of about 68. These groups were compared to a control group.
Ashkenazi Jews, who are of Eastern European descent, are remarkably similar in their genetic makeup. This makes them ideal for studies such as this one which seek to find single genetic mutations.
As it turned out, the Ashkenazi elders and their offspring were three times more likely than the control groups to have a DNA alteration in the cholesterol ester transfer protein (CETP) gene, which helps regulate blood levels of, and size of, HDL and LDL molecules. The mutation resulted in lower levels of CETP in the blood, increased levels of HDL and larger HDL and LDL molecules.
Why would larger particle size protect against heart disease, stroke and metabolic syndrome? No one knows the exact reason. It's possible larger LDL particles can't penetrate artery walls and contribute to atherosclerosis.
It's also not entirely proven that this is a cause-and-effect relationship. On the other hand, Barzilai says, he can look at the health of the subjects in his study and predict accurately who has large lipoprotein size and who does not. "It's a strong association," he says.
The study participants also seem to be proof of the contention that genes can override the environment. One 103-year-old woman just celebrated 95 years of two-pack-a-day smoking. "We know that we should exercise and diet and not be overweight, but the important thing with those guys was something downstream," Barzilai says. "They could do whatever they wanted."
Of 300 elders that Barzilai has interviewed (some after this study was completed), 30 percent were overweight and he can not find a single lifestyle factor that would explain their longevity. The main thing they had in common was parents who had lived a long time.
Now that the gene mutation has been discovered, the next logical step would be for a pharmaceutical company to find a drug that replicates the effect of that "downstream" gene.
Barzilai, for one, would take it. He has a family history of high cholesterol and is currently taking two drugs and exercising to stay healthy. His cholesterol levels are fine, but the size of his particles are small. Meanwhile, Pfizer is in the advanced stage of trials for a drug that would increase the size of HDL particles. "I'll certainly take that instead of the other drugs and measure the size," he says.
His aim, he says, is not necessarily to live longer but to live healthier. "What I'm after is better health," Barzilai says. "It happens that the mechanisms that I'm looking at will also extend life span and I apologize for that, but that's the way I tackled this problem."