March 15, 2005, Updated September 13, 2012

The gene CETP regulates lipoproteins (shown here) – substances that shuttle cholesterol and triglycerides through the bloodstream. Only one in 10,000 people will celebrate a century of life, but research by an Israeli-born scientist may increase those odds in the near future.

Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in the Bronx, has led a study that has identified three genes that can lead to a long, healthy life.

Barzilai’s team studied 300 Ashkenazi Jews between 95 and 108 years old and their children, many of whom have already lived beyond the average lifespan – 77.6 years.

“People with exceptionally long lives offer us a short-cut in understanding diseases and what prevents them,” Barzilai told Newsday.

Barzilai’s team were looking for genes that are more common in these families. A specific form of any one of the three genes recently identified showed up in 30 percent of these families, compared to 5 percent of people from families without a history of longevity.

One of the genes, called CETP, is present in 8 percent of 65-year-olds and the incidence jumps to 25 percent in those who make it to 105. CETP regulates lipoproteins, substances that shuttle cholesterol and triglycerides through the bloodstream. It also plays a role in increasing the good form of cholesterol, HDL. Those who inherit this rare form of CETP have larger lipoprotein particles in their blood.

The scientists are now trying to understand why these larger particles would be more protective than smaller ones. They are also endowed with good cognitive function. By contrast, half of people over 85 suffer from Alzheimer’s disease or another form of dementia.

Barzilai said that he and his colleagues have confirmed that the CETP gene mutation occurs more often in another population of elderly people without Alzheimer’s compared with those with the mind-robbing disease. He reported these findings earlier this week at a scientific meeting on dementia, sponsored by Albert Einstein College.

Another longevity gene identified is apoC-III, also involved in lipid metabolism. The third gene is APM1, which is involved in the regulation of insulin and the inflammatory process. It’s not clear how this rarer form of APM1 leads to longer life. But they did find that the levels of adiponectin, a hormone made by the gene, are higher in the centenarians and their children, and even higher in those with superb cognitive function.

These discoveries suggest that scientists could one day develop medicines that manipulate proteins made by longevity genes.

That day may not be far off. Barzilai said that Pfizer has created and is testing a cholesterol-lowering drug that seems to do the same thing CETP does.

Scientists have long argued that environment plays a more important role than genes in determining lifespan. “I have people who have smoked for 75 years, others who eat lots of meat and little vegetables and others who have never exercised,” Barzilai said. Thirty percent of the centenarians in his study are overweight or obese. “The genes seem to protect them from environmental risks,” he said.

Indeed, some of the centenarians look and act physically and mentally 30 years younger than others, he added. He’s not sure why.

The doctor believes that the good form of cholesterol, HDL, is key to a long, dementia-free life. “Give me a 100 year old and let me measure her HDL and I can tell you how good her cognitive function is,” he said.

Barzilai was the chief medic of the Israeli army before enrolling at the Technion Israel Institute of Technology in 1985. As a medical student he provided medical assistance at third world locations, such as at a refugee camp in Cambodia (1979-80) and at a clinic of the Kwazulu homeland in Africa (1983), and conducted biomedical research at Baylor College, NIH, and The Royal Free Hospital in London.

His residency was in Medicine and Geriatrics at Hadassah Hospital (Hebrew University) and at Yale University. His residency was in Medicine and Geriatrics at Hadassah Hospital (Hebrew University) and at Yale University. Barzilai then trained in Endocrinology and Molecular Biology at Cornell University Medical College and at The Albert Einstein College of Medicine.
Barzilai is the Director of the Institute for Aging Research at the Albert Einstein College of Medicine. He is currently an Associate Professor in the Department of Medicine, Molecular genetics and the Diabetes Research Center and is a member of the Divisions of Endocrinology and Geriatrics. He is also the Director of the Montefiore Hospital Diabetes Clinic.

Barzilai’s interests focus on the basic mechanisms on the biology of aging. He was the recipient of the prestigious Beeson Fellow for Aging Research and the Senior Ellison Foundation award. Barzilai has published nearly 100 peer-reviewed papers, reviews and chapters in textbooks.

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