The blood of extremely old individuals brims with large lipid particles, according to a study of 213 Ashkenazi Jews with an average age of 98. The research, which also included the centenarians' offspring, found too that many of the subjects carry a gene variant that influences cholesterol balance. But how this variant and lipid particle size might stave off death isn't clear.
Studying human longevity is no simple task. Worms and flies carry single genes that, when mutated, dramatically prolong life, but nothing that clear-cut has been found in humans.
Geriatrician Nir Barzilai of the Institute for Aging Research at Albert Einstein School of Medicine in New York City, endocrinologist Alan Shuldiner of the University of Maryland School of Medicine in Baltimore, and their colleagues gathered blood samples from three groups: centenarians, their children (who might have inherited longevity traits), and, as controls, 75 of the children's spouses and 183 other individuals from the Einstein Aging Study. Adding genetic diversity were similar data from the Framingham Heart Study, a cohort that's been scrutinized for decades.
The group tested levels of total cholesterol and its components of "good" or high density lipoprotein (HDL), "bad" or low density lipoprotein (LDL), and triglycerides. There was little difference between the centenarian-plus-offspring group and the controls, although some centenarian families had high HDL levels. As a last resort, Barzilai and colleagues tested the size of HDL and LDL particles, and they hit pay dirt. Eighty percent of centenarians had either large HDL or large LDL particles, or both, compared to 40% and 55% among controls. Offspring fell in between, and the numbers were lowest in the Framingham cohort.
Barzilai's group also tested for a gene that produces cholesteryl ester transfer protein (CETP). CETP shifts cholesterol molecules from HDL to LDL: Inhibiting CETP helps raise HDL. The researchers found that 25% of the centenarians had a specific CETP gene variant that blunts CETP activity, compared to 8% of controls, they write in the 15 October Journal of the American Medical Association.
"We really need to pay attention to this," says Jean-Pierre Després, director of research at the Quebec Heart Institute in Quebec City, Canada. It's striking, he adds, that LDL particle size, and not LDL levels--the target of drugs and heart disease prevention efforts--appears key. Still, the team's results will likely be debated for some time. Neither particle size nor CETP is "a predictor of whether you're going to become a centenarian," because most people with the good variant will still die before 100, says James Vaupel, director of the Max Planck Institute for Demographic Research in Rostock, Germany. A crystal ball for predicting life span, if it exists, is probably years off.