Wednesday, December 27, 2006

Die smarter? Longevity genes, Alzheimer's and gambling with Faust

The 'related links' section of this SciAm summary are also of interest:
Science & Technology at Scientific Single Gene Could Lead to Long Life, Better Mental Function -- A variation of a gene that controls the size of cholesterol molecules in the bloodstream is common among elderly Ashkenazim who remain mentally sharp

... Those centenarians who passed were two to three times more likely to have a common variant of a particular gene, called the CETP gene, than those who did not. When the researchers studied another 124 Ashkenazi Jews between 75 and 85 years of age, those subjects who passed the test of mental function were five times more likely to have this gene variant than their counterparts.

The CETP gene variant makes cholesterol particles in the blood larger than normal. The researchers suggest smaller particles can more readily lodge in the lining of blood vessels, leading to fatty buildups, which are a risk factor for heart attacks and strokes.

Whether or not this gene variant protects the brain by preventing this buildup, or through some other mechanism, remains uncertain, says Barzilai. Future research should also investigate whether this gene has an effect on dementia associated with Alzheimer's disease, says pathologist and human geneticist George Martin at the University of Washington.

Pharmaceutical companies are currently developing drugs that mimic the effect of this gene variant, says Barzilai. Unfortunately, one known as torcetrapib, manufactured by Pfizer, was pulled in December due to increased death and heart problems among study subjects, "but others in development aren't seeing that, so it might just have been a problem with that drug," says Barzilai. "If not, it's a question people might face--whether or not people want to prevent Alzheimer's even if there's a small risk of getting a heart attack.

Fascinating basic science, but like all good basic science it mostly raises questions. For all we know now this gene doesn't so much provide longer life, as kill off those who lack some other compensatory gene that provides benefits. It might, for example, be primarily an Alzheimer's reduction gene that also increases the risk of heart attacks, so if you sample elderly people with the gene you're finding those who have some other factor that offsets the heart attack effect.

Alas, many "beneficial" genes turn out to have a Faustian component -- such as trading slower aging and faster healing for more cancer. (Turns out mice do this big time -- if they're not killed they almost always die of cancer -- but they heal fast.)

Which brings us to Barzilai's comment. The promise of modern pharmacogenetics is really about optimizing the Faustian bargain. So you make a "deal with the devil", but the deck is stacked in your favor. If your MI risk is low but your dementia risk is high, then you might opt for an anti-dementia drug that increases the risk of MI. If your dementia risk is high, and your MI risk is average, you schedule bypass surgery in 8 years. Who needs recreational bingo when you can gamble on this scale?

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