Another possibility may relate to differences in who the two studies surveyed—Rush looked at a population of European ancestry; the 523 Bronx subjects in the JAMA study came from a mixed racial and ethnic background. The gene variant might have different effects in different groups. Could that be why the Ashkenazi centenarians shine?
Maybe. But it still might be a long shot. Findings that the CETP variant enhances cognition and general well being in old people have been equivocal. Some studies have shown benefit, others haven't. Desultory outcomes in gene association studies often mean that a single gene may have a relatively weak effect, if any. "It's important that we try hard to understand how genes affect diseases of later life but we need to moderate our expectations of what we can expect to find," says Tom Kirkwood, a biologist from Newcastle University in England. (See “Why Can’t We Live Forever” by Kirkwood in the Sept. 10 Scientific American.)"All the indications are that we're most unlikely to find that single genes make big contributions, and we're likely to need to develop rather more sophisticated ways of probing and interpreting the data than we have at present."
The CETP dispute is not the only one of recent vintage. Earlier this year researchers from Boston University retracted a paper published in Science that purported to have found 150 genetic variants linked to extremely long lives, though the investigators said they plan to submit their results to another journal.
The race to probe the genomes of the very old continues. The Archon Genomics X PRIZE, which kicked off this year, will award $10 million to the first team to sequence the genomes of 100 centenarians in an effort to unlock clues to healthy aging.
Interest in CETP for improved cognition in the elderly has not flagged either. Several drugs under development would inhibit production of the CETP protein in the same way as the gene variant purportedly tied to longevity does. The rationale: Lowering CETP results in higher HDL, which may protect against heart disease. "The question is if it will be relevant to cognition or just to cardiovascular endpoint," wonders Nir Barzilai, one of the Einstein researchers.
Drug companies like Merck and others have sunk millions into development of CETP inhibitors. Could cognitive decline be a side effect of these drugs? Probably not, but it still might be a question worth asking.
Recruitment for a drug trial to test effects of these drugs on cognition would be fascinating: Subjects would be recruited to see if a CETP inhibitor improves mental functioning or whether it may speed decline into dementia. Any volunteers?