CIBCB Day 2

I woke up this morning at 5am in Toronto. It's now midnight, and I'm in Guelph. A long day, but a very interesting one. I'd like to say it's made the last few days worth it, but I don't think my sense of humor has recovered yet.

The 5am start was because I wasn't sure how to get from the hotel where I was staying to the Renaissance downtown. Turns out that all metro systems are pretty similar, and I made it without too much hassle[1]. Today's schedule was two parallel sessions, so I didn't see everything, but I think I managed to catch most of the bits that interested me.

I chaired the first session, on gene networks, and gave the last talk in that section. Most of the talks were about reverse engineering gene networks from microarray data. Since I'm in the middle of a review which covers this area, I was particularly interested. It's a topic which is a natural for a computational intelligence approach, since the problem is desperately underdetermined; there's just not enough data to solve it. Added to which there are multiple networks which will produce the same gene expression pattern, the structure of the actual networks is unknown, and DNA-protein interactions are certainly not the whole story, and it becomes apparent that the problem is non-trivial.

My opinion, which was not substantially altered by today's talks, is that it can't yet be done. Current algorithms work pretty well on small, artificial networks, but don't scale to realistic network sizes, and the networks they produce cannot be properly validated. It's still an interesting area, though, and well worth working on. The insights and algorithms developed now may well be much more practically valuable when applied to the larger, more complete data sets which undoubtedly be generated over the next few years.

There were good sessions in the afternoon on Biological Theory and RNA structure and function. The latter was mostly algorithms for predicting RNA secondary structure from sequence data. Since we're starting to realise just how important RNA is, I think we'll be seeing a lot more of this sort of work in the next few years. And RNA structure might be easier to predict than protein structure, which is another largely-unsolved problem with huge biological implications[2].

Went to dinner tonight with a group of female bioinformaticians, an occurrence which is as rare as it is enjoyable. Then the train to Guelph, and, hopefully, some sleep in preparation for another day of talks tomorrow.

[1] Apart from the hotel desk clerk, but we won't go in that...
[2] Or then again, it may not.

Still in Transit

It's not the first time I've woken up in a room full of strangers who are carefully not looking at me, with my face adhering to black vinyl and a chair arm sticking into my back, but the last time was 20 years ago, and I have to confess I'd be perfectly happy if the next time is 20 years in the future. Still, a night spent in gate lounge 5F was not as bad as I'd feared. Breakfast in Murphy's pseudo-Irish Pub was a bit surreal, though [1], not least because it appeared to be full of Geordies.

To add insult to injury, the plane was delayed by nearly an hour. If it had been delayed that much yesterday, I would have caught it! I made it to Toronto in the end and am currently ensconced in a hotel, showered, chip-fed and manicured[2]. I've missed the first day of the conference, but fortunately my talk is tomorrow. I'm chairing the session, too, and it starts at 8:30, so something tells me tomorrow is not going to be a lot less frantic than today. At least it will contain some science, though!

[1] I've always been concerned that my scrambled eggs are not as light and fluffy as they could be. But at least I don't do that to them!
[2] I've broken a fingernail, though...is this really worth it?

Traveller's Tales

I'm on my way to the IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology, in Toronto. Something tells me it's going to be another one of those trips...

I was up at 5am, after a disturbed night's sleep; I never sleep well when I'm afraid of missing the alarm. Bathed, dressed, packed, fed, on the metro by 7, which wasn't too bad. Arrived at the airport to find that only one bag was allowed, but I had a laptop and a handbag. Put the laptop in the handbag, various important, delicate and almost certainly soon-to-be-stolen-or-smashed items [1] into the laptop bag, and checked it in.

And then the flight from Newcastle to Amsterdam was delayed due to bad weather. The flight itself consisted of two hours in the gate lounge, 45 minutes sitting on the runway, then 50 minutes in the air, enlivened by a dry cheese sandwich. I'm so glad I had that double gin at 8:30am... Upon arrival, we were told that those Toronto-bound had missed the connection. After half an hour in line at the transfer desk (a doddle, compared with those at the end of the line, but I can do a mean sprint from arrival gate to transfer desk, even in high heels) I was told that the next flight is tomorrow afternoon. And because the delay was due to weather, the airline won't pay for a hotel. So it's a night in the gate lounge for me, and I'll miss the first day of the conference.

Mr Lloyds-TSB grudgingly parted with 50 euros, via a handy ATM (not a given, three days before payday!), so I'm in a bar, paying airport prices for average chardonnay, and plotting. Apparently there are recliner chairs in some lounges, so at some point I'll go try and intimidate someone into vacating one. Not that I expect to sleep. I wonder what the crime rate is in Schipol airport?

[1] Including the power supply for the laptop, so this connection is strictly a limited option. I'll try and save half an hour's worth of battery for 3am, when things are most likely to get desperate.

Are We Evolving?

I don't ask this with the aim of engaging any creationists[1], but because it is a legitimate question to ponder. There are two schools of thought. One argues that Homo sapiens is no longer evolving, since the advent of modern medicine means that we can keep alive-and even reproducing-people who would otherwise die. On the whole, proponents of this view seem to think it's a bad thing. They skate perilously close to eugenics, with the (usually implicit) view that those of us with "bad genes" should at least have the decency to die, leaving the gene pool nice and tidy. "Bad genes" are apparently a lot like pornography - "I can't define it, but I know it when I see it!" The only certainty is that those bemoaning the rise of the genetic underclass have no doubts about the goodness of their own genes.

Exactly the opposite point of view is held by those who believe that the amazing developments in practical genetics over the last 50 years or so mean that, not only are we evolving, but we can control the direction of our own evolution. Media stories [2] about the potential and problems of "designer babies" are rife. If any of these reporters had actually tried introducing a desired gene into a eukaryote (and yes, I have!) they'd be a lot more circumspect. That's not to say that we'll never be able to design tall, blonde, intelligent, beautiful offspring to order[3], but I seriously doubt whether we're yet directing our own evolution.

I suspect the bottom line is that we're just as subject to the vagaries of natural selection as any other species. We really don't understand the day-to-day mechanics of natural selection; the concept of "fitness" is about as vague as you can get, and in practice is measured in terms of reproductive success. For a species with a generation time as long as humans (15 - 20 years), there just hasn't been time for us to affect evolution in any significant manner, whether by medicine or by genetic engineering. I'd be willing to lay odds we're still evolving.

[1] I have colleagues who are more than capable of doing this - go for it, Matt!
[2] Even my favourite, New Scientist, has been known to succumb to designer baby hysteria.
[3] I produced tall, blonde, intelligent, beautiful offspring the old fashioned way, and it seems to be working so far. A bit less tall would have been good, though, so they couldn't lean on me when they feel patronising.

Camels

OK, this has absolutely nothing to do with ageing (I don't even know the lifespan of a camel, offhand), but this has got to be one of the coolest photographs I've ever seen:

Check it out!

Death is the Price you Pay for Sex

At least, that's what Lynn Margulis says. Between you and me, I've never really understood what she meant, but it sounds vaguely evolutionary-theory-PC, so I just nod knowingly. But according to Reuters, 40% of Brits would give up on sex if it meant living to 100, so it looks as if quite a proportion of the population isn't prepared to pay the price.

Now the disclaimer: the Reuters article says it's research done by Mori on behalf of BUPA, but I can't find anything about it on either of their websites. So it's impossible to judge what sort of questions were asked or what the results mean. I assume, for example, that by "living to 100" they mean a healthy, active 100[1]. And the sample demographics might be interesting; I should imagine a group of nuns would be much happier giving up sex in favour of longevity than a group of prostitutes.

But despite the caveats, it's an interesting question. From an evolutionary point of view, once you've reproduced you might as well die (unless you can help perpetuate your genes by being a grandparent)[2]. But people are amazingly selfish, and seem to prefer to stay alive. But giving up sex? This is where we need the text of the survey. Did the respondants really mean they'd be prepared to sacrifice the chance to reproduce, or just that they'd give up going to the Bigg Market on Saturday nights? Given that 94% apparently said they wouldn't give up their friends or family in order to make the century, I'd guess the latter. And, let's face it, that's not such a big sacrifice.

The alternative, of course, is to live fast, die young and leave a good-looking corpse.

[1] Although they won't get a telegram from the Queen; apparently she sends cards these days!
[2] This is a shocking simplification, and I'm ashamed of myself. I'll do a proper posting on it later.

You're Getting Sleepy...

Interesting review in Nature today about the interplay between sleep and weight gain. There seems to be an increasing amount of evidence indicating that people who are short on sleep tend to gain weight. This seems a bit weird, until you realise that the areas of the brain that control fatigue and sleep overlap with those that control appetitite. So you won't necessarily get fat if you're sleep-deprived (a relief, I'm sure, to all our hard-working students!), but you will tend to get the munchies. The answer, as it is so depressingly often, is not to give into temptation. Sigh.

So, this lead me to wonder...is there a link between sleep deprivation and longevity (I would expect it to be negativbe, if it exists). I did a quick search on Google Scholar (where have my scholastic pronciples gone?!) and it seems, not unsurprisingly, that there hasn't been a lot of research in the area. There's an article intriguingly titled "Mammalian sleep, longevity, and energy metabolism" in Brain, Behaviour and Evolution from 1974, but my library doesn't carry that one. I might order it on interlibrary loan, of I ever get around to returning thebook on the history of RNA that's nearly a year overdue. If I set foot in the actual, physical library I expect sirens to wail and lights to flash, while armed guards appear from behind the stacks. Or maybe I'm just being self-aggrandizing here! Anyway, if I can find it I'll post a summary.

Offhand, I'd be willing to bet that there is a relationship between hours of sleep and general health, which would translate, at least to some extent, to longevity. Whether there's a more direct connection, like that between sleep and appetite is less certain, but would be an interesting area of research.

Lasker Awards

The 2006 Lasker Awards for Basic Medical Research has been awarded to Elizabeth Blackburn, Carol Greider and Jack Szostak for the prediction and discovery of telomerase. Fantastic!

Telomerase is the enzyme which maintains the (surprise, surprise) telomeres. These are the bits on the ends of the chromosomes. Every time a chromosome is copied the telomeres get shorter, and it is widely believed that this contributes to the ageing process. When the telomeres get too short, it appears, the cell dies. Telomerase is generally not active in adult cells, so one form of anti-ageing therapy might involve activating telomerase.

This is, unfortunately, a dangerous thing to do. Cells with active telomerase are immortal, and the type of immortal cells we know best are, of course, cancer cells. It turns out that cancer cells do have active telomerase; once again, cancer is the flip side of ageing. So any intervention based upon telomerase would have to take into account all of the complexities of the system, which we are just beginning to understand. It's a very active area of research, and a fascinating one.

What's Wrong With "Old"?

I've just been watching Saturday afternoon TV (I know, but I'm trying to avoid working on a very overdue paper!) and was confronted with Jane Fonda selling face cream. Now, leaving aside the fact that none of these creams actually do anything, what really annoyed me is the way that the clearly-surgically-enhanced Ms Fonda refers to the skin which has benefited so much from this elixir (as opposed to plastic surgery) as "very mature". In the ad she mentions, with commendable sang-froid, that she's 68. Why the euphemism? Jane Fonda is old. Mature as well, but why boggle at "old"? It seems to be the ultimate crime in our society. It's OK to have lots of years under your belt, as long as you've had enough work done that you look like Barbie. And never use the o-word.

A great illustration of this attitude is the recent appearance at some awards show [1] of Charlie's Angels, who are now in their 60s. Lots of media coverage raving about how good they still look. If you're a devotee of plastic surgery, they're poster children. And I'll bet not one of them would label themselves "old".

Well, I have sympathy with that. But the problem lies, not with the fact of ageing, which is inescapable [2], but with the pandering to the perception that only young-looking women are attractive. Given that assumption, "old" is a killer word: if you're old you're a non-person. It applies to men, too, but less so. We all think Sean Connery is gorgeous, and most of us would admit he's old. But we still probably wouldn't use the word!

Life isn't about sex. Personal value shouldn't be about sexual attractiveness. There's nothing wrong with being old - the alternative is much worse![3]

[1] Sorry, wasn't paying attention. Something media-related; I'm pretty sure it wasn't the Nobels.

[2] Until my research centre sorts it out, of course!

[3] And actually, I happen to think that old women can be gorgeous, too, but then, I have a vested interest!

Longevity Records

If the Guinness Book of World Records says it, it must be so...the Seven-figure pygmy goby Eviota sigillata is officially the shortest-lived animal on the planet, strutting its stuff on the world's stage for a mere 59 days at the most, of which three weeks are spent as larvae, leaving two weeks into which to cram its entire reproductive life. It takes me longer than that just to get a date...

For completeness, I should point out that the world's lonhest lived animal (and indeed, longest lived organism) is the Hexactinellid sponge Scolymastra joubini, according to the Human Ageing Genomic Resources website. It cheats, though, (the sponge, not the website) by living in the Antarctic, where the very low temperatures keep metabolisms slow. The site admits that the estimated maximum age of 15,000 years may be an overestimate, but even so, it's a long, long time to hang around the Ross Sea. Puts Departmental Meetings right into perspective!

For the record, Homo sapiens comes in at #16, which isn't bad going. We're the only species to have our lifespan[1] recorded to decimal precision, too.

[1] 122.5 years

Starving for Longevity

...or maybe it just makes life feel longer. I'm talking, of course, about caloric restriction, which has been shown to produce significant life extension-up to double the normal life span- in species as diverse as worms, flies and mice. Not only do they live longer, but they appear to age more slowly, developing all those fun, age-related diseases like cancer and atherosclerosis later in life.

We don't really understand the mechanisms involved, so we have no idea whether the same effect will be seen in humans; studies in monkeys and apes only began in the 1980s, so results are just starting to come through. They look promising, but we won't be able to say for certain for another decade or more. But that, of course, doesn't stop people from experimenting on themselves. There's a pretty committed community of caloric restriction practitioners, many of whom are represented by the Calorie Restriction Society. They do preach good nutrition, and talk about some of the risks of practicing calorie restriction, so it looks harmless enough, on balance, although I can't help feeling that going through life trying not to eat is a mindset best left to teenage girls, and quickly outgrown.

But will it work?

There is a school of thought that argues that whatever the mechanism by which CR works, it must have evolved under some sort of selection pressure. And the pressure may well be something along the lines of a short lifespan with a rapid metabolism in an environment where you can't guarantee when you'll see your next meal. Under these circumstances, it makes sense to be able to slow your system down, hence deferring reproduction, under conditions of food scarcity. Mice fit this model nicely, although I'm not so sure about worms.

If, however, this is the underlying rationale for the anti-ageing effects of CR, it might not apply to humans, since we are already big and relatively slow, have a long reproductive lifespan, and evolved in the nuturing plains of Mother Africa. It's all hypothetical, of course, but I find it a moderately convincing line of reasoning. Biology, after all, is all about evolution. So I think I'll steer clear of the CR crowd for now. I'd hate to spend the 32 years I have left hungry, with nothing to show for it in the end.

Food for thought (OK, I know...obvious, but it had to be said!)

Good News and Bad News About Longevity

We all know that life expectancy is increasing. My Illustrious Leader, in his Reith Lecture in 2001 tells us that 0ver the course of the last half-century, life expectancy has increased steadily by two years each decade. At the start of the 19th century it was around 40; today it is about 75 for a man and 80 for a woman, and still increasing. So that's good news.

But there's bad news, as well. The major aim of gerontologists (apart from finding people able to pronounce the name of their specialization) is to increase the number of years of healthy life lived. The hope is that illness will be compressed into a shorter part of the lifespan; rather than being elderly and frail for 30 of those 40 extra years we aim to be lively octagenarians, getting the arthritis and osteoporosis over with after we've finished mountain climbing and water skiing. But recent statistics released by Australian Institute of Health and Welfare indicate that this may not be the case. They show that as lifespan increases, the proportion of life lived with disability increases. Men can expect to live for 18.6 years with a disability severe enough to affect day-to-day living, while women are looking at a depressing 20.7 years of disability, on average.

Now, according to the life expectancy quiz I did the other day, I can expect to live to 79, unless I mend my evil ways (and there's no sign of that at the moment). I'm currently 47 (and Australian), so I have 11 healthy years ahead of me[1]. Something tells me I might have left that career as a world class Marathon runner too late.

Of course, the bad news doesn't have to continue; this research was done using statistics from 1988 to 2003. There's an awful lot of research being done into healthy aging[2] and the results are yet to make themselves felt. I think most people woud agree that a longer old age filled with pain and medication is not that much of a boon. If we're going to live longer anyway, we desperately need to find out how to live healthier, as well. Right, I'm off for a run!

[1] Yes, of course it's ridiculous to apply population-based statistics to an individual. It's poetic licence, ok?
[2] Obligatory plug for the IL's 85+ Study, which is going to generate lots of lovely data.

Living to 100?

I've just done the online quiz at http://www.livingto100.com[1]. Interesting, but I'd take its recommendations with a grain of salt. The quiz consists of 40 questions, covering all the sorts of things that you'd expect to be considered important - diet, smoking, alcohol consumption, wearing selt belts, etc. It gives you an estimate of your life expectancy and then some "personalized feedback" which is clearly just canned responses to the options available in the quiz.

The good bits: Most of the questions make sense in the light of what's known about aging, and the recommendations they give are generally valid, although most of them are common sense (eat lots of fresh fruit and vegetables, don't have risky sex...)

I had a couple of problems, though. For a start, the site is clearly commercial. Not a problem, really, but it does make you wonder how unbiased the recommendations are. Further, there are no references to the literature, so no indication why various recommendations are made. One example is aspirin; the site says, and I quote, "if you really don't have a reason to not take an aspirin a day, consider taking one daily. 81 mg of Aspirin per day has been noted to significantly decrease heart disease risk". Now, this is true, but I really don't think it's a good idea to advise individuals to self-medicate based on group studies. As a fit, middle aged, vegetarian, non-smoking female I may or may not benefit from aspirin, but I'd rather be assessed individually than start taking what is actually a quite powerful and surprisingly poorly-understood drug daily for the rest of my life (however short that might be!). And how do I know if I really don't have a reason to take an aspiring a day?

Similarly, the advice to floss every day to avoid heart disease is based on recent, and relatively unsupported, research. It may well be perfectly correct, and it certainly can't hurt to floss, but the advice gives a spurious air of certainty to a finding which is still not solid.

The other bee in Dr Perls' bonnet is screening. Screening for high blood pressure, cholesterol, etc. can be valuable, but it's not a panacea for all ills, and people tend to forget that mass screening tests usually have high error levels. They have to be quick, cheap and non-invasive, and those constraints are rarely compatible with high accuracy and specificity. Might be a blog topic to go into in more depth later! I think the best way to safeguard your health is to be familiar with your body and aware of its functioning, and the risks inherent in whatever lifestyle you choose to lead, so that you can tell when something changes. I'm not anti-screening, but I think measures like the currently-fashionable whole-body MRI or CT screening are at best a waste of money. At worst they can provide a false sense of security, or even add risk by increasing exposure to radiation.

Despite these issues it's an interesting site, and provides generally valid advice[2]. And it was nice to be told I'm a "lean, mean fighting machine"! I'd still love to know how they put a number on life expectancy, though.

Oh, and for the record, I'm only going to live to 79...maybe I should get some of that screening done!

[1] Disclaimer: I have no connection with the site or the good Doctor. I actually came across it via a mention in New Scientist.
[2] I did love the line " Great news that you have not had a heart attack." I thought so, too!