Gene Tied To Longevity Also Preserves Ability To Think Clearly

Led by Dr. Nir Barzilai, director of the Institute for Aging Research at Einstein, the researchers examined 158 people of Ashkenazi (Eastern European) Jewish descent who were 95 or older. Compared with elderly subjects lacking the gene variant, those who possessed it were twice as likely to have good brain function based on a standard test of cognitive function.

Later the researchers validated their findings independently in a younger group of 124 Ashkenazi Jews between the ages of 75 and 85 who were enrolled in the Einstein Aging Study led by Dr. Richard Lipton. Within this group, those who did not develop dementia at follow up were five times more likely to have the favorable genotype than those who developed dementia.

Dr. Barzilai and his colleagues had previously shown that this gene variant helps people live exceptionally long lives and apparently can be passed from one generation to the next. Known as CETP VV, the gene variant alters the Cholesterol Ester Protein. This protein affects the size of "good" HDL and "bad" LDL cholesterol, which are packaged into lipoprotein particles. Centenarians were three times likelier to possess CETP VV compared with a control group representative of the general population and also had significantly larger HDL and LDL lipoproteins than people in the control group.

Researchers believe that larger cholesterol particles are less likely to lodge themselves in blood vessels. So people with the CETP VV gene (and the larger cholesterol particles they produce) run a lower risk of heart attacks and strokes, which may explain their unusual longevity.

The findings of this new study suggest that CETP VV also protects the cognitive integrity of the brain--either through the same vascular "anti-clogging" benefit that prevents heart attacks and strokes or through an independent protective mechanism that remains to be found.

"Without good brain function, living to age 100 is not an attractive proposition," says Dr. Barzilai. "We've shown that the same gene variant that helps people live to exceptional ages has the added benefit of helping them think clearly for most of their long lives. It's possible that CETP VV's cognitive effect is to protect against the development of Alzheimer's disease. In studying these centenarians, we hope to learn why they're able to resist diseases that affect the general population at a much younger age. This knowledge should greatly aid our efforts to prevent or delay the onset of age-related diseases."

Other Einstein scientists involved in the study were Dr. Gil Atzmon, Dr. Carol Derby, Dr. Jonathan Bauman and Dr. Richard Lipton. The study was supported by grants from the Einstein Aging Study, the Paul Beeson Physician Faculty Scholar in Aging Award, the Ellison Medical Foundation Senior Scholar Award, the National Institutes of Health, the Albert Einstein College of Medicine, and the Baltimore VA Geriatric Research and Education Clinical Center.