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Science/Tech
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Title: Can a blood test really tell you when you'll die?
Source: [None]
URL Source: http://www.guardian.co.uk/science/2 ... ommentpage=2#start-of-comments
Published: Oct 13, 2011
Author: Giles Tremlett
Post Date: 2011-10-13 07:41:19 by Tatarewicz
Keywords: None
Views: 56
Comments: 2

A small Spanish biological research company was deluged with queries after reports that its blood test could predict the age you would die. Well, can it?

As a taxi takes me across Madrid to the laboratories of Spain's National Cancer Research Centre, I am fretting about the future. I am one of the first people in the world to provide a blood sample for a new test, which has been variously described as a predictor of how long I will live, a waste of time or a handy indicator of how well (or badly) my body is ageing. Today I get the results.

Some newspapers, to the dismay of the scientists involved, have gleefully announced that the test – which measures the telomeres (the protective caps on the ends of my chromosomes) – can predict when I will die. Am I about to find out that, at least statistically, my days are numbered? And, if so, might new telomere research suggesting we can turn back the hands of the body's clock and make ourselves "biologically younger" come to my rescue?

The test is based on the idea that biological ageing grinds at your telomeres. And, although time ticks by uniformly, our bodies age at different rates. Genes, environment and our own personal habits all play a part in that process. A peek at your telomeres is an indicator of how you are doing. Essentially, they tell you whether you have become biologically younger or older than other people born at around the same time.

The key measure, explains María Blasco, a 45-year-old molecular biologist, head of Spain's cancer research centre and one of the world's leading telomere researchers, is the number of short telomeres. Blasco, who is also one of the co-founders of the Life Length company which is offering the tests, says that short telomeres do not just provide evidence of ageing. They also cause it. Often compared to the plastic caps on a shoelace, there is a critical level at which the fraying becomes irreversible and triggers cell death. "Short telomeres are causal of disease because when they are below a [certain] length they are damaging for the cells. The stem cells of our tissues do not regenerate and then we have ageing of the tissues," she explains. That, in a cellular nutshell, is how ageing works. Eventually, so many of our telomeres are short that some key part of our body may stop working.

The research is still in its early days but extreme stress, for example, has been linked to telomere shortening. I think back to a recent working day that took in three countries, three news stories, two international flights, a public lecture and very little sleep. Reasonable behaviour, perhaps, for someone in their 30s – but I am closer to my 50s. Do days like that shorten my expected, or real, life-span?

People with similar worries – or, perhaps, just Woody Allen-style neuroses about their health – have begun to contact the company set up by Blasco. Requests have poured in from around the world since a headline writer at the Independent, perhaps misled by Life Length's ambiguous name, invited readers to find out about "The £400 test that tells you how long you'll live." The internet did the rest.

Originally set up to help researchers and the pharmaceutical, health food and cosmetics industries test the impact of their products on telomeres, the flood of individual requests has caught Blasco's still tiny company by surprise. But the test is available, as of this month, via doctors in Spain and Portugal and there are plans to make it easier to carry out in the UK and the US as soon as possible. It sees a potential gold-mine in testing of what it calls people's "biological age" – though it is by no means alone in the field. So what can Blasco tell me about my test?

"You actually have very good news," she says, pointing at a chart that looks as if it has been blasted by shotgun pellets. My telomeres – especially the more dangerous, shortest ones – are in better shape than would be normal for my age. The pellet points are individual results from those people who have been tested and introduced into this database so far, and the red dot representing my blood sample is on the better side of the two graphs Blasco shows me. One graph shows median telomere length, while the other shows how many crucially short telomere endings I have. In each case, a line on the graph shows the average result against age. The test on some 100,000 of my telomeres, compared with the other results on the admittedly small database being used by Life Length when this test was done in the summer, give me a "biological age" six years below my real age. With only 90 other men on the chart so far, all with different lifestyles and genetic backgrounds to mine, I should avoid feeling smug. Eventually, when there are thousands or more on the database, I might get a better idea of what results people more like me should expect. I have a reasonably healthy lifestyle, after all, and previous generations on both sides of my family have been long-lived.

However, according to a New York Times interview with 2009 Nobel prize-winner Carol Greider – whom Blasco trained under – individual telomere tests are not much use. "The science really isn't there to tell us what the consequences are of your telomere length," she said.

Blasco, obviously, disagrees. So does Elizabeth Blackburn, who shared the Nobel prize for telomere research with Greider and Jack Szostak, and has set up her own Telome Health company to start offering tests later this year.

Blasco compares the current state of telomere testing to the early days of cholesterol tests – and believes it should become common once the price drops and research is done to beef up databases, improve interpretation and create telomere-restoring treatments. "This is a different kind of marker. It is a new, molecular marker. Even though we measure telomere length in blood cells, it has been shown to be an indicator of the degree of telomere shortening in the whole organism," she says. "And we think it is very powerful, based on what we know from hard science." Even so, she is insistent that the test is not a magic measure of individual life length. "We don't tell anyone how long they will live.

"It is the doctor – and we want to do this with doctors – who will tell you what is known about the meaning of this measurement and what you can do and what you cannot do," says Blasco. In fact, the benefits of telomere science still lie mostly in the future. As with early cholesterol tests, a doctor is currently unable to tell you much about what those results mean – or what you can do about a bad result, beyond fairly obvious advice about looking after your health.

I notice that a few of the 90 men on my chart have apparently alarming results. Their telomeres indicate a "biological age" 20 years or more higher than their real age. This means that, at least statistically, they may be much closer to death than most people their age. One of these men comes from a family with a long history of early cancers, according to Life Length's CEO Stephen Matlin. He has offered those with worryingly high results a free second test after three months, to see whether anything has changed. My report also warns, however, that results may reflect temporary illness or ongoing medical treatments – effectively skewing them. And some results on the chart look plain bizarre. One tester, for example, appears to have – at least statistically – a biological age of around 120. Two people aged above 60, together with a clutch of 30-year-olds, have an estimated biological age below zero – presumably because their telomeres are in better shape than might be expected of the average baby. Life Length said this reflected the fact that little research had been done on the telomeres of the very young.

Individual testing, then, is still in nappies. Far more exciting are the possible future advances to come from telomere research, says Blasco. "One is telomerase activation, because of its potential to reverse ageing. And proving which diseases can benefit from telomerase activation, in order for this to be something druggable."

"Some of the new [research] papers appearing in top journals are to do with telomorase activation," she says. "That is one aspect. The other is that we are seeing a lot of epidemiological studies showing correlations between telomere length and certain diseases, and which habits are good or bad for telomere length."

She says the idea that telomeres can be "re-elongated" and, hence, that biological age can be reversed does not open the door to immortality – even if scientists have been able to extend a mouse's age by up to 40%. "That's a lot, but nobody has been able to make a mouse that is immortal," she says.

It does, however, throw up philosophical and ethical dilemmas. The US Food and Drug Administration (FDA), for example, refuses to approve drugs that are simply designed to prevent ageing. "Although I – and many more scientists – believe ageing is the cause of diseases, this is not perceived like that yet by the FDA," says Blasco. "But what is clear is that there are a number of diseases associated with ageing which are caused because our cells age."

Activating telomerase to counter that, she says, might help prevent major illnesses and allow drugs to be approved by the FDA. If drugs are found to activate telomerase and prevent, say, Parkinson's disease, Alzheimer's disease or some cardiovascular problems then the inevitable result will be not just a healthier life, but also a longer one.

Blackburn agrees that the idea that the new tests can tell you your life length is silly, but she insists that the evidence connecting telomere length and disease risk is becoming clearer.

"We and other groups are seeing clear statistical links between telomere shortness and risk for a variety of diseases that are becoming very common, such as cardiovascular disease, diabetes and certain cancers," she told the nature.com website in August. "We have also looked at chronic psychological stress, including depression and post-traumatic stress disorder, and more and more we see associations with telomere shortness. There are even links with education – in one study telomere shortness was related to not finishing school. We're seeing the data unfolding in front of us. A lot of them are not published yet."

So what has telomere testing done for me? Not a lot, frankly, though I might have reacted differently had I been dangerously off the chart. Nor am I a woman in her 30s, who might like to know how fast the biological clock that may eventually limit fertility is ticking.

I am tempted to repeat the test again, mainly out of a competitive desire to get better, but only if (as on this occasion, when Life Length waived the $500 fee) I can get it for free. Far more interesting, however, has been the glimpse of the future – when telomere testing, and popping pills to repair the tips of our chromosomes, may allow us to live both longer and healthier. I am persuaded, too, that the aim should be to make sure we live our years out in good health. So why all the rushing about? Time, perhaps, to take things more calmly.

Comments: bloodandbone As a molecular biologist I need to point out that telomere science is not in its infancy, it is reasonably well understood. It is not the basis of cellular aging, although it does contribute in some ways to the aging phenotype. Over-expression of telomerase will not make you live forever, it will give you cancer:

www.pnas.org/content/99/12/8191.full

Aging is a pleiotropic phenomenon, not a pre-programmed timing mechanism, and because we don't understand a lot of the underlying cell biology we really don't know how to control it .... other than caloric restriction (lay off the burgers).

Tom Kirkwood has written some insightful reviews on aging e.g.

www.sciencedirect.com/sci...cle/pii/S0092867405001017

This is not difficult science.

This story could have been written ten years ago, I learnt all this as an undergraduate in 2000, except that no-one had tried to make money out of it at that stage (as far as I know). Recommend? (139)

frglee Isn't there's a clock you can buy that after you feed in all your details,estimates how long you have left ?[maybe using acturail tables?] You activate it and then it starts ticking backwards to zero hour. I can't imagine why anyone would want that on their mantlepiece. Sounds horribly morbid to me. But no doubt insurance companies are aching to het hold of this test....

frglee i dont know if there is a clock to buy but there is a website that does the same thing www.deathclock.com/

richard57 The U.S. company that owns many patents on Telomeres is called Geron and are based in Menlo Park ,Ca. check out their website...very interesting.

imipak I can see how that might extend the life of biotech companies, but I don't see how that would extend the life of anything else.

@bloodandbone: The study of genetics didn't stop with Crick and Watson. It didn't even stop when the human genome was sequenced. All that happened was that we discovered that genes interact a lot more than we expected, didn't always code to what we expected, and were controlled by the environment (starting with that of the grandmother and continuing to the present) via the inheritable portions of the epigenome. And, of course, the epigenome was itself a total shock to geneticists. Of course, it got worse when genetic tests started showing that heteroplasmy wasn't uncommon.

Telemeres are "old hat", sure, but since it's impossible to measure them across all cells, it's impossible to know how they vary across cells. Telemeres are indeed linked to the aging process, but the exact relationship is unclear. The aging process also appears to be genetic, but the genes purportedly involved have never been found (as far as I know).

In short, genetics (as with most other sciences) is riddled with claims of almost complete understanding, followed by the discovery that what had been known was merely a crude approximation of a very small part.

These groups that purport to measure telemere length can do no such thing for you as a person, they can only measure a very small number of cells. The assumption that these cells are representative is just that, and there is absolutely no basis at this time for making that assumption.

Taking the median length, the mean, or just the shortest, is then a gross simplification of what little is known about aging and the role telemeres play in it. The usefulness of the number(s) produced is anyone's guess at this time precisely because the science of everything else is so much in flux.

And that's the key point. Cells are all about extremely complex interactions, they are NOT about single properties. The notion of isolated, compartmentalized bits has been so utterly and ruthlessly destroyed beyond all imagining that anything you may have learned about telemeres is AUTOMATICALLY false.

We know more than we did in the 1990s, only much of that knowledge has told us that we actually know less now than what we thought we knew back then. Recommend? (11)

imip

@RedShowDave: Take a squint at the 1000Genome project or the 23AndMe website. Those are fairly complex.

Monkeybiz: Although I – and many more scientists – believe ageing is the cause of diseases, Hmm. This seems to be a bit like saying that age is the cause of corrosion in a car. Does a car need to have a set of instructions to avoid corrosion? No, corrosion is an entropic process, which requires work to resist. So depending on how good the starting state of the car is will depend on how long it lasts. There is a good argument that it is physiological reserve, which is built up in childhood and teens to maximize reproductive fitness, that is important. After peak reproductive age (late teens early 20's) this reserve declines, and as such, so does the body's capacity to resist entropic effects. Some process can modify the rate of this process - for example - smoking (akin to washing your car in sea water), diet and exercise, but not reverse it. The Laws of Thermodynamics means that there is only ever one direction for this process, namely towards greater entropy. Once a certain level of entropy is achieved, organ malfunction emerges as a clinical sign or symptom.

The trouble with all such tests is that they are only really of use at a group level, if it indeed turns out that T length is relevant to longevity, and not subject to lengthening/shortening as a result of other intermittent variables (e.g. diet, exercise etc.). They are based on group probabilities, just like you can say there is a high chance someone will win the lottery. The trick is predicting who and when, and with which set of numbers. That's nigh impossible.

Tawny Answers such as this are so old school newtonian physics that assume that the only factors that determine when you will die are physical/material. People with the most unhealthy lifestyles, or voracious diseases can WILL themselves to live longer than any would think. Similarly, there is documented evidence of people dying because of thier beliefs (voodoo; santeria; doctor telling you, you have 6 months to live..)

The question should also be- what is the point of living? Is it just to live as long as possible? Would you rather have a relatively short but fulfilling life full of love. laughter etc, or a long, boring and fearful life of grey bleakness? I guess ideally, a long and fulfilling life...but worrying about how long you are going to live, isn't going to help achieve that...

If it makes you happy (and doesn't hurt anyone else) do what you like. Smoke, drink, eat whatever. But here is a little suggestion, try to do it peacefully and with awareness. Focus on enjoying that moment like there is no other. There might not be, but at least you will have lived that moment fully.

muscleguy @Bloodandbone Extreme caloric restriction does seem to lengthen life, on average. But the latest data suggests that it is not that these diets are low in calories that makes them work but that they are also low in protein. It supposedly works via IGF-1, the more protein you eat the higher your overall IGF-1 levels and we know high chronic IGF-1 does things like cause inflammation and that is bad for cancer, heart disease etc.

What we don't know is how that relates to those of us who exercise. When you are very active you need quite a lot of protein. So does that give me high IGF-1 or do I escape because I exercise? Or do all the elderly people on caloric restriction health nuts who are healthier because of that, not the caloric restriction? Doing this in humans is very much messier than in inbred mouse lines in cages in the mouse house.

I both look and feel younger than I am. I think I know lots of men my age (and younger) who look much older than me. But am I just prey to the positive bias fallacy?

Your point about lengthening telomeres and cancer is a good one but I expect the link won't be direct. Cancers only get going once the second hit that stops the damaged cells committing suicide, it is likely to be there that telomeres come in. You want the telomeres of the cancer cells to be short, if they are long then beating it will be tough (and the fight will shorten the telomeres on your healthy cells). So long telomeres are a good thing, unless you have nascent cancer cells AND the sort of immune system that doesn't get them all.

Germanlady Activating telomerase to counter that, she says, might help prevent major illnesses and allow drugs to be approved by the FDA

But as I understand it, such a test is able to tell the degenerativ state of the telomeres, but can not give an indication, what it is caused by (i.e. genetic or environmental factors) and what lethal disease will be the result. All it does, it gives you a statement, far less meaningful tthan traditional tests on your inner organs by means of your pulse, blood pressure and urine/fecal/blood tests. So it may cause anxieties, but can not provide answers of what can be done to improve your life expectations. Sounds unhealthy to me.

PJMolloy She says the idea that telomeres can be "re-elongated" and, hence, that biological age can be reversed does not open the door to immortality – even if scientists have been able to extend a mouse's age by up to 40%. "That's a lot, but nobody has been able to make a mouse that is immortal," she says.

Oh yeah? What about Mickey?

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#1. To: Tatarewicz (#0)

deathclock.com claims I'll croak at 94.

(No way I'll live that long.)

No way.

Break the Conventions - Keep the Commandments - G.K.Chesterson

Lod  posted on  2011-10-13   13:12:07 ET  Reply   Trace   Private Reply  


#2. To: Tatarewicz (#0)

no mention of body pH wrt the environment that our cells live in ?


"If you love wealth more than liberty, the tranquility of servitude better than the animating contest of freedom, depart from us in peace. We ask not your counsel nor your arms. Crouch down and lick the hand that feeds you. May your chains rest lightly upon you and may posterity forget that you were our countrymen.”—Samuel Adams

Rotara  posted on  2011-10-13   15:52:46 ET  Reply   Trace   Private Reply  


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