Telomere length as a biomarker of stress and aging

One of the more noodle-baking results I heard last year was the surprising report that psychological stress correlates inversely with telomere length in peripheral blood cells, at least in one sex of a twitchy, intractable model system (H. sapiens). From Epel et al. (second author is telomere grand dame Liz Blackburn):

… Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases.

I once watched Dr. Blackburn fielding post-talk questions at a Buck Institute symposium. (She later told me, with a hint of exasperation, that she gets asked the same questions over and over again at conferences when she talks about this work, sometimes by the same people who asked same questions at the conference immediately prior).

One of the questions (that had been asked by the same person before) boiled down to a spluttering, “But how can that be?” followed by a very reasonable mechanism that might explain the data: the relative abundance of subpopulations of leukocytes with different telomere lengths could change in response to stress. Liz’s response was to equally reasonably point out that the experiments were done properly, the phenomenon is real, but the mechanism is admittedly still up for grabs — and to argue that any mechanism would be interesting to know about, whether it’s the effect of stress on subpopulation growth rates, telomerase expression, division rate in a precursor cell compartment, or something else altogether.

We’re somewhat closer to understanding something about the molecular mechanisms. From another Epel et al. (same Epel, different al., with Blackburn in the senior position this time):

… Here we examine whether telomere length and telomerase in leukocytes are associated with physiological signs of stress arousal and CVD risk factors in 62 healthy women. Low telomerase activity in leukocytes was associated with exaggerated autonomic reactivity to acute mental stress and elevated nocturnal epinephrine. Further, low telomerase activity was associated with the major risk factors for CVD … Telomere length was related only to elevated stress hormones (catecholamines and cortisol). Thus, we propose that low leukocyte telomerase constitutes an early marker of CVD risk, possibly preceding shortened telomeres, that results in part from chronic stress arousal. …

So increased stress seems to correlate with depressed telomerase activity in the leukocytes, keeping in mind (1) all cautions about not inferring correlation with causality, and (2) the fact that any number of variables not studied might also be varying at the same time, including the relative proportions of leukocyte subpopulations, vide supra.

Since these two seminal papers were published, the idea of telomerase activity and telomere length as markers or proxies for illness (or the risk of illness) has been gaining broad traction. Two sympathetic reviews and one primary paper on a related subject came out this week:

  • Abraham Aviv argues in favor of using telomerase as “an index of `somatic fitness,’ a concept that breaks down the artificial boundary between aging and diseases of aging”;
  • Brümmendorf and Balabanov discuss telomere length as a readily measurable endpoint that might help identify and distinguish disease states such as chronic leukemia and bone marrow failure; and
  • Harris et al. describe an (admittedly modest) inverse correlation between cognitive ability and telomere length at age 79.

One of my fantasies (and I think it should be the fantasy of every biogerontologist) is to be able to walk up to a human subject with my handy futuristic and minimally invasive device, and make a measurement to determine how old they are. I don’t mean their chronological age, but rather how old they are really — let’s call it “physiological age”, a value that would (in the fantasy) be more powerfully predictive of risk for age-related disease and decline. Intuitionally and anecdotally we know that different people simply age at different rates, but at the moment it’s painfully hard to quantify what we mean by that.

I don’t necessarily think telomere measurements are a magic biomarker bullet, but these results make me wonder whether they might end up being an important button on the tricorder part of the toolkit.

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9 comments

  1. This would be a valuable test for anyone over say 50, to determine rate of aging and potential for many different diseases that stress the immune cells. I think it could be commercialized, and will be before long.

  2. As a scientist involved in telomerase and telemore length related work I find this article to be thought provoking. The ‘aglets’ may reveal many more things in the years to come.

  3. And where does a stressed out/cortisol loaded woman go for a telomere length test? Any research that this effect is reversible? Thanks for the news, by the way — I am intrigued.
    Z.

  4. Ok, This is all good but where do we get our telomere’s test at?
    What lab?
    Phone number please!
    http://www.23andme.com test sort of for this.
    I’ve been looking and only found
    nuerologist or peditritions can test.
    I want to test mine. I have chronic stress
    with chronic cancer/illness.
    I would be willing to be a doctor’s genypig!
    Are there any studies out there?

  5. Man, I did my senior research project on the effects of catecholamines on telomerase and telomere length 10 years ago (theoretical). At the time, the only responses I got from academia were “why on earth would you think those are related?” Sweet vindication!!!

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