May 19 2011

How Long Will You Live?

A UK company plans to begin selling a blood test that purports to tell you how long you will live. This, of course, sets off an immediate red flag – how can one blood test determine something so complex as life expectancy? Such skepticism is probably justified.

The test, which will cost $700, measures the length of one’s telomeres. Telomeres are the caps at the ends of chromosomes, often compared to the aglets that cap the ends of shoelaces. The purpose of telomeres is to protect the ends of chromosomes during copying. The enzymes that copy each strand of DNA that makes up each chromosome cannot read to the very end of the string, so each time a chromosome is copied a bit of the end is left off. If needed genetic information went all the way to the end, then a bit of this information would be lost with each copying, causing problems. So each chromosome is capped with a non-coding bit of DNA, the telomere (a repeating sequence of TTAGGG in all vertebrates), and a bit of that is cropped off each copying cycle instead of useful genetic information.

Telomeres would then become shorter and shorter until the cell could no longer divide. However, there is an enzyme called telomerase that lengthens the telomeres, thereby maintaining them (called telomere homeostasis). (As an aside, there is also an alternative mechanism for the lengthening of telomeres.)  However still – telomerase is mostly active in fetuses and babies and then becomes progressively repressed in most adult tissues. Therefore, despite some ability to maintain telomere length, the length does tend to shorten as we age.

The reason for the suppression of telomerase is to reduce the risk of cancer – the same reason that we do not have unrestricted stem cells regenerating all of our tissues. We apparently evolved to live long enough to reproduce and raise our young to reproductive age, not to be immortal.

The question with regard to telomere length – what is the relationship to aging and disease? Length may be a cell marker for these things, but do shortened telomeres cause aging or are they just a result of aging. If the latter, then developing treatments to artificially lengthen telomeres will not necessary slow, stop, or reverse aging or disease.

The jury is still out on this question. But there is a lot of evidence to suggest that telomere length plays, at least partly, a causal role in aging and disease. It has been associated, for example, with risk of developing rheumatoid arthritis. Telomerase activity is also important in maintaining immortal cell lines in culture. But biology is complex, and we currently only have a partial picture.

Therefore the notion that telomere length has a relationship to longevity is not crazy. It is legitimate, if preliminary, science. It is an exciting area of research, and while I doubt it will lead to a cure for aging, it may lead to important treatments in the future.

But what about the notion of a blood test for telomere length to determine how long you will live? This is not based upon science, and in fact is a misreading of the existing science. The idea behind this blood test confuses longevity or lifespan with life expectancy. The former is the potential length of one’s life, and is plausibly related to telomere length – although this has yet to be established.

However, how long someone will live is more closely tied to their life expectancy (a statistical statement about how long someone will actually live), and this has to do with numerous factors. For example, the life expectancy of a soldier on the front lines of a deadly war is a lot shorter than would be indicated by any health measure. But even if we leave the risk of accident or injury aside, and just consider medical issues, there are many factors such as diet, exercise, smoking, alcohol use, sleep, body mass index, cholesterol level, and other factors that have nothing to do with telomere length that have a demonstrable effect on life expectancy.

Simply measuring telomere length has an unclear relationship to lifespan, and even if it did have a predictive relationship it does not consider all the important factors that influence life expectancy, which is what people really want to know anyway. In short – this blood test will not tell you how long you will live.

I also have not even considered the generic issues that must be considered for any such test: what is its predictive value, and with what sensitivity and specificity? It will take years to sort out these questions (since we are dealing with how long people will live, which by definitions takes many years of follow up to determine). The best we can do in the short term is retrospective studies, and these are plagued with uncontrolled variables.

There is the further question of what an individual can do with this information. In medical decision making the rule of thumb is never to order a test unless you know exactly what you will do with the results. Otherwise you risk getting abnormal result that you cannot act upon, or do not know how to act upon. If someone orders this test  – what will they do with the results, no matter what it shows. If they have longer telomeres than average for their age, is this license to be reckless with their health? If they are shorter than average what can they do about that? You might say they can improve their lifestyle, but they should do that anyway.

It seems the only outcome of such a test is to instill either unnecessary anxiety or a false sense of security. The fact that this test is being offered by a private company direct to the consumer is a disturbing trend that I have written about before. Some companies seek to jump the gun on the science, and take preliminary scientific knowledge to market filled with hype and false promise. But it sounds very sciencey. It is likely to either be worthless (and therefore a scam) or, at worst, a health menace.

There aren’t really any effective regulations targeting this problem (and as usual, one can debate the relative risks and benefits of such regulation), so for now it’s buyer beware.

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