Tuesday, December 26, 2006

Ageing Genes Back in the News

There's an interesting report in yesterday's (26 December) issue of Neurology: researchers in the US have identified a gene which is reponsible both for longevity and for the retention of mental sharpness. "Wow!", thinks I, "my work has been done for me, we can all go home." So I downloaded the paper[1]. Now, I think this is a very nice piece of work, and has some intriguing implications. I have issues, not with the paper itself, but with the way it's being reported.

Looking on Google News[2] yields the following headlines:

"Longevity Gene Also Keeps the Mind Sharp"
"Gene Tied to Longevity Also Preserves Ability to Think Clearly"
"Longevity Gene Also Protects Memory, Cognitive Function"
"'Supergene' Gives Long Life, Clear Mind (I love this one! Does it also enable you to leap tall buildings at a single bound?)
"Study: Gene Tied to Long Life Wards Off Dementia"
...and on, and on.

The most moderate is probably "Gene Tied to Longevity May Protect Brain", but who can really resist "Gene Aids the Elderly"? Or even "Single Gene Could Lead to Longer Life, Better Mental Function"?[3]

OK, so what did they really find?

The study took 158 people aged 99, and looked for the presence of a gene variant previously associated with longevity (CETP VV, a gene whose protein is involved in lipoprotein metabolism). They also gave their subjects a test known as the Mini-Mental State Examination (MMSE), and looked for correlations between MMSE scores and the presence of CETP VV. They did, indeed, find a statistically significant association between the presence of the allele and high test scores; hence the media hysteria. But, of course, the picture is not that simple.

The authors state that "Subjects with good cognitive function had a higher frequency of the CETP VV genotype than those with poor cognitive function (29% vs 14%, p = 0.02)". Further, "those with the CETP VV genotype were twice as likely (61% vs 30%, p = 0.02) to have good cognitive function than those witht the II genotype." OK, those numbers look reasonably interesting, but when you consider that only 43.5% of the group had "good" cognitive function, and only 24% had the "good" allele, it's clear that the gene is not the only factor at work here, by a long shot. In fact, if you translate the percentages into absolute numbers, there were 20 people with good cognition and the good allele, compared with 12 with poor cognition and the good allele. If the traits are independant, you would expect 16 (24% of 43.5% of 158 people) people to have both the good varieties, just by chance. It may be a significant difference, but it's a hardly a "supergene".

In addition, the mechanism of action of the good allele isn't known. The researchers suggest that it may be related to the previously-identified link between CETP VV and low incidences of heart disease, or it may be a completely new pathway. If it's something as simple as increasing blood flow to the brain, then maybe its beneficial effects can be achieved by something as simple as increased aerobic exercise, rather than tinkering with the mode of action of a crucial metabolic pathway.

So, to summarize:

It's a nice paper, and the results are interesting and may direct research into useful areas.
1. It's a small study (158 people)[4];
2. The results are only just statistically significant;
3. Other factors (other genes, environment, nutrition, exercise...) appear to be more important in influencing the phenotype than the gene itself;
4. "Cognitive function" was measured with a single test.

Neither the general public, nor the researchers, nor science itself is done any good by hyping results such as these into news of supergenes which are going to turn us all into centenarian geniuses. It's never that simple.

[1]Barzilai, N., Atzmon, G., Derby, C. A., Baumann, J. M. & Lipton, R. B. (2006). A genotype of exceptional longevity is associated with preservation of cognitive function. Neurology 67: 2170 - 2175.
[2] http://news.google.com/news?hl=en&ned=us&ie=UTF-8&ncl=1112251435
[3] Scientific American, how could you?
[4] The results were validated with a larger sample, but it's still a small, preliminary study.

Tuesday, December 12, 2006

Integrated Functional Networks

Well, I finally made it Australia, after a flight which I prefer not to remember in too much detail[1]. Today I gave a seminar at the School of Information Technology and Electrical Engineering at the University of Queensland, my old stomping ground.

I haven't been back to Aus for a year, but it feels as if I've never been away, despite the fact that I've done a lot of work in the past year. The seminar was about what I've been doing in Newcastle; integrated functional networks as per the title of this post. I've only been working on this for a year, but I think we're now in a position to identify both the promise and the challenges of this approach.

What's an integrated functional network? It's a network of interactions between proteins within a cell. The interactions are identified by scanning as many as possible of the large data sets that are currently available, generated by lots of different technologies. Different types of interactions are combined using a statistical approach, and the result is a network in which links between genes mean that there is some sort of relationship between those genes. Each link has a weight which reflects the probability that it really exists, given the evidence we have.

These networks are a hot topic of research at the moment, because they take data that is tucked away in big databases and makes them available to biologists with specific research questions. Many of the big pharmaceutical companies are using them to identify potential drug targets, for example. We're hoping to use them to guide research into the genetics of ageing.

So I gave the talk, and got some valuable feedback, and then we went to lunch, which was great, since the people there were all old friends and colleagues. The slides are going to be online somewhere at some stage; I'll post an update when they go up.

From the sublime to the ridiculous: tonight's the University Staff Club Trivia Night finals, and my (ex) team is competing. I'll be there to cheer them on (and maybe drink a champagne or two!).

[1] Why do the nutters always want to talk to you at 2am when you're trying to watch "Finding Nemo"?

Saturday, December 09, 2006

Dubai, or not Dubai?

I'm officially in transit to Australia, to spend Christmas with my family. I'm actually in Dubai, which has its pluses as well as its minuses.

I left home at 8:00am Friday, to catch an 8:30 train to London. Arrived 12:00; another hour on the train to Heathrow and then 45 minutes in the Emirates check-in line. When I actually got to the desk it was a little galling to find that I'd actually been in the wrong line; my first leg was with Virgin Atlantic. Still, these things can happen to anyone! I moved to the Virgin line, and finally managed to check in. Seven hours from leaving my front door to walking through security, and I haven't even boarded the plane.

We did board - eventually. Only about an hour late, but enough to make us miss the connection to Brisbane. So I'm spending the night in Dubai. An interesting city.

At first they were proposing to put us up at the Marriott, but it turned out that all they had were executive rooms, at an equivalent of $500US per night. "Oh, yes!" I was thinking. "At last, the life I should be living!" Alas, it was not to be. We're at the Arabian Park, a perfectly adequate hotel, but not exactly the high life.

They think big in Dubai. The buildings are big (although some are cool and curly, but not many). The roads are big, and the traffic is appalling. I went to a (big) shopping mall to get some money from an ATM, only to come face to face with a dilemma. I have no idea what the currency is, or how it translates to dollars (Australian or American) or pounds. So I'm looking at the ATM, and it's teling me that I can withdraw up to 3,000 somethings. The minimum is 200; I choose to go with 600, which is the second lowest option. I may just have cleaned out my bank account, and made it impossible to pay the rent this month; or I may have about two pounds in my purse, and will be totally humiliated when I have to pay my internet access bill in the morning. It's these little nuances that make international finance so interesting.

I'm currently in bed, with a wake up call booked for 4am. With any luck I'll be home in another 12 hours, but I have Singapore to negotiate yet. The way my recent trips have gone, I'm not optimistic, although I gather you can make a good living as a street theatre artist at Singapore airport, so all is not necessarily lost. One of these days I'll get back to doing science...

Monday, December 04, 2006

Cheap wine and a 21-day growth

Yes, it's red wine revisited. I've previously mentioned the depressing finding that you need to drink 300 glasses of red wine a day in order to get mouse-verified levels of life-extending resveratrol. Tempting, but impractical, not to mention expensive, even if you go for one of the co-op's cheaper options. But this week's Nature carries a report that it might not just be resveratrol that is the essential longevity-promoting ingredient in red wine. Apparently there's another set of chemicals, irresistably named "oligomeric procyanidins", abundant in wines from Nuoro province, Sardinia, and southwest France, which appears to act against blood vessel constriction. And people from these regions apparently have "higher than normal average longevity". As a loyal Aussie, and a long-term devotee of Australian reds, this news disturbs me.

So should we move from the Brown Brothers Merlot to one of those French wines with the unpronounceable names? Maybe. There seems to be some evidence that the Tannat grape, which is grown in these areas, is particularly rich in procyanidins. But another factor seems to be the fermentation process; apparently traditional wines in these regions undergo a 21-day fermentation process, in which the juice remains in contact with the skins and seeds (and seeds are where the procyanidins lurk). Most wine has a shorter fermentation process, and so the wine ends up absorbing less of the active ingredients.

I have to admit I've never tried wines from Sardinia. Maybe it's time to give them a go. Any recommendations?