Is that glass half-empty, or half-full? Be careful – your answer may result in telomere shortening!

We all know people, be they friends, family or colleagues, who seem to have a permanently downbeat view of life. Worryingly for them, research over the last few years has indicated that a negative outlook for the future has been associated with both faster progression of age-related disease, and earlier mortality. Furthermore, telomere attrition occurs with age, and being at the wrong end of the telomere length distribution at any given age is associated with increased risk of a number of diseases, including cardiovascular disease.

So it should come as no surprise to learn that chronic psychological stress has been associated with accelerated telomere shortening in circulating white blood cells. The problem arises in trying to provide a biological mechanism that links this form of stress to increased telomere loss. To address this, a group including the telomere/stress heavyweights Epel and Blackburn noted that both acute and chronic stress have been associated with increased interleukin-6 (an inflammatory cytokine), and repeated bouts of inflammation are associated with telomere shortening. Thus the authors set out to link stress (in this study the measure was optimism vs. pessimism) to telomere shortening via IL-6 in a cohort of post-menopausal women:

Pessimism correlates with leukocyte telomere shortness and elevated interleukin-6 in post-menopausal women.

The combination of less positive and more negative expectations for the future (i.e., lower optimism and higher pessimism) increases risk for disease and early mortality. We tested the possibility that expectancies might influence health outcomes by altering the rate of biological aging, specifically of the immune system (immunosenescence). However, no studies to date have examined associations between optimism or pessimism and indicators of immunosenescence such as leukocyte telomere length (TL) and interleukin-6 (IL-6) levels. We investigated whether dispositional tendencies towards optimism and pessimism were associated with TL and IL-6 in a sample of 36 healthy post-menopausal women. Multiple regression analyses where optimism and pessimism were entered simultaneously, and chronological age and caregiver status was controlled, indicated that pessimism was independently associated with shorter TL (beta=-.68, p=.001) and higher IL-6 concentrations (beta=.50, p=.02). In contrast, optimism was not independently associated with either measure of immunosenescence. These findings suggest that dispositional pessimism may increase IL-6 and accelerate rate of telomere shortening. Mechanistic causal relationships between these parameters need to be investigated.

As with the previous Epel/Blackburn paper (showing that “intrusive thoughts” impact on telomere length), the psychological measures (optimism, pessimism and perceived stress) were all based on questionnaires. As a molecular biologist who is accustomed to running standardized assays I will always have a little trouble when the data comes from a subject assigning a score to a comment such as, “If something can go wrong for me, it will”. I worry that there is such a subjective element to this type of study, but appreciate that in psychology there is little alternative.

This relatively small study of 36 post-menopausal women comprised 81% white subjects. Given the recent observations that ethnicity impacts on telomere length, it would have been sensible to include subjects from a single ethnic group to reduce the number of confounding variables. (There is no mention of any impact of ethnicity on telomere length, or if it was even considered as a confounder.)

There is also evidence that telomere attrition rates may differ in pre- vs. post-menopausal woman, a phenomenon that may be related to telomerase stimulation by estrogen. Therefore, it is pleasing to see that all subjects were post-menopausal (the authors have previously correlated perceived stress in post-menopausal women with shorter telomeres, but stress that this study is a different cohort).

The study reported a significant, negative association between IL-6 and telomere length, although the authors clearly state that this is not proof of causality: it may be that it is the critical shortening of telomeres that triggers inflammation rather that the other way around. Of the psychological measures optimism was not associated with either telomere length or IL-6, while pessimism is associated with both. This observation feels slightly counter-intuitive; is reduced pessimism not the same as increased optimism? If so, one would expect that if pessimism associates with shorter telomeres then surely optimism would associate with longer telomeres? Clearly this is not the case. As in the previous Epel/Blackburn study, higher levels of perceived stress were also associated with shorter telomeres, leading to the conclusion that “exposure to psychological stressors in pessimists could contribute to to chronic low-level increases in circulating pro-inflammatory cytokines…contributing to telomere shortening”. While this was a small study, it does add weight to the hypothesis that an individual’s psychological disposition is a contributing factor to poor health outcomes.

Cause for further concern for our downbeat friends is that an individual’s score on optimism and pessimism measures generally remain stable across time (important to note that this was not assessed in the present study, but has been replicated in earlier studies). Unfortunately for the happy folk out there, optimism again fails to associate with “better” health outcomes — so we may as well all take the middle-ground on this one.

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