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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

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May 14, 2002

After Natural Selection's Through With You

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Posted by Derek

There's an interesting article on aging in the latest issue of Current Biology. The researchers used gene-chip assays, which look at over 13,000 genes simultaneously for signs of up- or down-regulation, in populations of aging fruit flies.

Fruit flies share a rather unnerving number of similar genes with other animals (all the way up to us,) and their short live span makes the attractive for this kind of study. What makes this one stand out is the amount of detail it goes into.

The team checked the flies at different time points, in multiple populations, and under conditions of normal aging and caloric restriction. That last technique - basically, living close to starvation - has been shown in increase life span in many species. There are some people trying it as well (you have to be pretty careful with your nutritional balance, and the question always comes up about how wonderful excess life span can be if you can't eat anything. . .)

This study also controlled for how much the various genes tend to vary. You can see some genes tripling in activity, and it means nothing, because they vary naturally even more than that. Others are so steady that almost any change (up or down) is news.

Gene chips have been all the rage for a few years now, and they're getting more powerful all the time. But not too many people control their experiments with them as well as this group did, which often makes it hard to figure out what the data are telling you. In this case, though, they saw about 800 genes that were definitely associated with age-related changes. Half of those changed whether the flies were calorically restricted or not.

Some of them were things that had already been picked up by other studies. But there are quite a few new ones (enzymes and proteins that inhibit them, proteins involved at the cell nucleus, and others) that no one had fingered before. This paper will be a road map for some time to come for those looking at aging.

And many are, or will be. I think that over the next ten to twenty years, this is a field that could really take off. What use is a longer lifespan if you spend your extra ten (or 20, or 30) years as an eighty-year-old? Let's add those extra years to the twenties, thirties, and forties instead.

This is just the sort of research that probably sends Francis Fukuyama up the wall, to judge from his recent book and op-eds. (There's been a huge pile of commentary in the Blogosphere about all this, which I assume people have seen.) It's true that changing the human life span will probably lead to all sorts of disruptions - but we've done it before. The last hundred years has been a huge experiment in lengthening the average life expectancy, but because it was done by improving mortality rates and nutrition, no one had any room to object. In the same way, no one objects to the long, slow genetic engineering that humans have been doing with their crops and domestic animals. It's just when things get more efficient that the alarm bells start to go off. . .

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