Wednesday, July 18, 2012

Stress and Telomere Length—Do You Believe this Study?

Healthy skepticism is an important part of science. One of the biggest differences between scientists and intelligent design creationists, for example, is that the creationists are rarely skeptical of anything they read in the scientific literature. If it appears to support their agenda, then it goes right onto the blogs without any discussion of whether it might be true or not.

Scientists, on the other hand, are often very skeptical of work that appears in the scientific literature. They treat most papers as tentative results that need to be confirmed. The most obvious flawed papers will be refuted by further work, as in the recent arsenic in DNA paper or earlier work on cold fusion. Usually, flawed papers will just be ignored and they will die a quiet death.

Not all scientists agree when healthy skepticism is appropriate. The junk DNA controversy is a good example of when scientists differ in their evaluations of the difference between good science and bad science. Proponents of junk DNA are skeptical about papers claiming that most DNA has a function even though the science in the paper seems sound. Opponents of junk DNA, on the other hand, treat such papers as real data and they are skeptical of papers that support junk DNA.

The point is not that individual scientists are always appropriately skeptical. The point is that science as a way of knowing works collectively and in the long run healthy skepticism is crucial to advancing knowledge.

How do you explain healthy skepticism to students? It's relatively easy to assign a paper to undergraduates and have them write up a summary for subsequent discussion. Sometimes you pick a paper that you know is probably wrong but it's extremely rare that the students will recognize this on their own. You can explain why you are suspicious and skeptical but what it really boils down to is experience. Mature scientists just have a "instinct" for what's right and what's not. I think it depends on whether the conclusions differ from your current model of how things should work. (Different scientists have different models.)

Experience can't be taught. That's one of the reasons why I'm a bit skeptical about having undergraduates delve into the primary literature.

Here's an example of a paper I just read (Ahola et al., 2012). There doesn't seem to be anything wrong with the science but I just don't believe the suggestion is true. I can't really tell you why. What do the rest of you think? Should scientists be skeptical of this work?
Work-Related Exhaustion and Telomere Length: A Population-Based Study

Psychological stress is suggested to accelerate the rate of biological aging. We investigated whether work-related exhaustion, an indicator of prolonged work stress, is associated with accelerated biological aging, as indicated by shorter leukocyte telomeres, that is, the DNA-protein complexes that cap chromosomal ends in cells.

We used data from a representative sample of the Finnish working-age population, the Health 2000 Study. Our sample consisted of 2911 men and women aged 30–64. Work-related exhaustion was assessed using the Maslach Burnout Inventory - General Survey. We determined relative leukocyte telomere length using a quantitative real-time polymerase chain reaction (PCR) -based method.

After adjustment for age and sex, individuals with severe exhaustion had leukocyte telomeres on average 0.043 relative units shorter (standard error of the mean 0.016) than those with no exhaustion (p = 0.009). The association between exhaustion and relative telomere length remained significant after additional adjustment for marital and socioeconomic status, smoking, body mass index, and morbidities (adjusted difference 0.044 relative units, standard error of the mean 0.017, p = 0.008).

These data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging. This hypothesis awaits confirmation in a prospective study measuring changes in relative telomere length over time.

[Hat Tip: Mike the Mad Biologist]

Ahola, K., Sirén, I., Kivimäki, M., Ripatti, S., Aromaa, A., et al. (2012) Work-Related Exhaustion and Telomere Length: A Population-Based Study. PLoS ONE 7(7): e40186. [doi:10.1371/journal.pone.0040186]


  1. Their results may have a degree of validity to them, given the cell types used. I doubt this finding would be true in non-hematopoietic tissues.

    The production and lifespan of immune cells is controlled, in part, by the HPA axis. Among the hormones produced by the HPA axis are those produced in response to stress. These hormones can reduce the half-life of leukocytes (which is one reason why chronic stress often results in sickness - you have fewer and poorer-functioning leukocytes).

    In response to this, the bone marrow does increase the production of immune cells - especially of neutrophils and monocytes (which combined comprise about 80% of the circulating leukocytes in a human). This requires more cell division of the stem cells, which in theory means the stem cells* (and thus the resulting neuts/mono's) may have shorter telomeres.

    I doubt many other cells in the body would react similarly. Moreover, I'm not even sure this possibility is true for immune cells - AFAIK, hematopoietic stem cells express telomerase, and therefore shouldn't experience much telomere shortening - even under conditions of increased hematopoiesis.

    1. That was my first thought as well. They are measuring an immune system phenomenon (and one that's fairly well known, at that), not biological aging.

    2. Yes, my take on it would be that "biological age" is an almost meaningless concept, and that telomere length is but one part of it (but yes, may be linked to stress in some cell types). To draw a more general conclusion that stress = aging? Nah.

  2. It took me forever to read papers when I started grad school, and I often (always?) missed key points. But my classes taught me how to read papers. Not by "teaching" in the sense of my profs telling us how to read papers, though they tried to give us a few tips. But by making us read papers, and explain them. Followed by the prof pointing out all the stuff we'd missed. 4-5 papers a week for a couple of semesters helped enormously. And it taught me that the scientific method is no proof against Sturgeon's Law...

    I can't think of a strong reason not to extend such an approach to undergraduate classes. Obviously there's a certain amount of background knowledge and familiarity with the jargon required, but I think a junior or senior level seminar class designed to immerse you in the literature could be great. Maybe fewer papers, but quantity is definitely a virtue here. And crap papers can teach you as much as good papers, so a mix is good.

    As for the paper: beware confounding variables. Or, when I'm feeling especially cantankerous: molecular epidemiology is bunk.

  3. Problem is, it's tough to explain to somebody without the same level of experience in a field why something is probably not true. In face, they could probably find a few papers that support the hypothesis that you're skeptical about.

    And these people probably have a lot of colleagues who aren't skeptical either. So the thing you don't believe ends up becoming fact for these people.

  4. Could be true for leukocytes, but leukocytes are destined for a very short lifespan in the periphery anyway. They should test hematopoietic stem cells, preferably in bone marrow or mobilized from bone marrow.

    1. Not necessarily a short lifespan; lymphocytes can live for years or decades, dividing very slowly in lymph nodes. But they divide rapidly when the immune system is stressed.

  5. Some of the authors were also involved in the paper "Alcohol dependence in relation to burnout among the Finnish working population" (Ahola et al. (2006) Addiction 101(10):1438-43
    Other people think ethanol influences telomere lengths: "Shortened telomeres in individuals with abuse in alcohol consumption" (Pavanello et al. (2011) Int J Cancer 129(4):983-92
    Thus, one may ask if the people suffering from burnout had problems with alcohol.

    At the same time you can find the following claims with a single MedLine search:

    Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study.

    Childhood trauma associated with short leukocyte telomere length in posttraumatic stress disorder.

    Investigation of telomere length and psychological stress in rape victims.

    The load of short telomeres is increased and associated with lifetime number of depressive episodes in bipolar II disorder.

    Telomere length and mental well-being in elderly men from the Netherlands and Greece.

    Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood.

    Childhood trauma associated with short leukocyte telomere length in posttraumatic stress disorder.

    Childhood adversity heightens the impact of later-life caregiving stress on telomere length and inflammation.

    Thus, people in the field really seem to beleave that telomere lengths reflects the psychological/mental status of a person.

    Strangely enough, the situation doesn't improve with thearapy because "differences in the applied therapy, the duration of illness, or the severity of depression do not seem to have any influence on telomere length."(Hartmann et al (2010): "Telomere length of patients with major depression is shortened but independent from therapy and severity of the disease." Depress Anxiety 27(12):1111-6

  6. I am a YEC creationist boy from Toronto.
    it was said in the thread "scientists" question everything in science journals etc etc. ID Creationists believe everything they read??
    The whole point to any creationist tribe is that we don't believe a great deal of conclusions in biology or geology etc etc.
    We are the sceptical movement of modern times!
    Not old time evolutionism.!

    Id or YEC exists in complete contrariness to the lingering thing called evolutionary biology or anything in nature that doesn't hint of a creator.
    The modern movement of creationism is sceptical , and quite punchy and growing, easily uses or rejects new ideas in publications and is a good judge.

    Evolutionists checking on spelling but missing whole themes is going to be the explanation in the future for why evolution or anything opposite to a creator took place.
    Watch folks!

    1. As usual, Booby Byers attempts to hijack a thread. His comment, such as it is, has nothing to do with the subject of the thread.

  7. Let's start with the following statement:

    These data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging.

    I am not convinced that telomere length is reliable indicator of the rate of biological ageing (usually defined as the increase in the age-specific mortality rate). Is there any study that shows that telomere length correlates well with this in humans? I doubt it.

  8. @Corneel,

    In mice, it does not correlate that well, either. One example...


    Telomere length and telomerase activity directly affect the replicative capacity of primary human cells. Some have suggested that telomere length influences organismal lifespan. We compared telomere length distributions in a number of inbred and outbred established mouse strains with those of strains recently derived from wild mice. Telomere length was considerably shorter in wild-derived strains than in the established strains. We found no correlation of telomere length with lifespan, even among closely related inbred mouse strains. Thus, while telomere length plays a role in cellular lifespan in cultured human cells, it is not a major factor in determining organismal lifespan.

    -The Other Jim