Perceived stress and telomere length: A systematic review, meta-analysis, and methodologic considerations for advancing the field

Abstract

Importance: Psychological stress contributes to numerous diseases and may do so in part through damage to telomeres, protective non-coding segments on the ends of chromosomes.

Objective: We conducted a systematic review and meta-analysis to determine the association between self-reported, perceived psychological stress (PS) and telomere length (TL).

Data sources: We searched 3 databases (PubMed, PsycInfo, and Scopus), completed manual searches of published and unpublished studies, and contacted all study authors to obtain potentially relevant data.

Study selection: Two independent reviewers assessed studies for original research measuring (but not necessarily reporting the correlation between) PS and TL in human subjects. 23 studies met inclusion criteria; 22 (totaling 8948 subjects) could be meta-analyzed.

Data extraction and synthesis: We assessed study quality using modified MINORS criteria. Since not all included studies reported PS-TL correlations, we obtained them via direct calculation from author-provided data (7 studies), contact with authors (14 studies), or extraction from the published article (1 study).

Main outcomes and measures: We conducted random-effects meta-analysis on our primary outcome, the age-adjusted PS-TL correlation. We investigated potential confounders and moderators (sex, life stress exposure, and PS measure validation) via post hoc subset analyses and meta-regression.

Results: Increased PS was associated with a very small decrease in TL (n=8724 total; r=-0.06; 95% CI: -0.10, -0.008; p=0.01; α=0.025), adjusting for age. This relationship was similar between sexes and within studies using validated measures of PS, and marginally (nonsignificantly) stronger among samples recruited for stress exposure (r=-0.13; vs. general samples: b=-0.11; 95% CI: -0.27, 0.01; p=0.05; α=0.013). Publication bias may exist; correcting for its effects attenuated the relationship.

Conclusions and relevance: Our analysis finds a very small, statistically significant relationship between increased PS (as measured over the past month) and decreased TL that may reflect publication bias, although fully parsing the effects of publication bias from other sample-size correlates is challenging, as discussed. The association may be stronger with known major stressors and is similar in magnitude to that noted between obesity and TL. All included studies used single measures of short-term stress; the literature suggests long-term chronic stress may have a larger cumulative effect. Future research should assess for potential confounders and use longitudinal, multidimensional models of stress.

Keywords: Cellular damage; Meta-analysis; Stress; Telomere.

Fig 1. The Stress Triad and Telomere Maintenance

Chronic major stressor exposures can lead to chronically high levels of perceived stress and subsequent stress arousal. In turn, chronic stress arousal is hypothesized to proximally impact telomere maintenance. To the extent that perceived stress over the month reflects a chronic state, and is related to stress arousal, there may be a relationship between perception and telomere length.

Fig 2

Fig 2A: Forest Plots of Unadjusted Correlation between Perceived Stress and Telomere Length Fig 2B: Forest Plot of Age-Adjusted Correlation between Perceived Stress and Telomere Length n.p. = not published. Fig 2A displays the unadjusted correlation. Fig 2B displays the age-adjusted correlation. Studies are displayed in descending order of weight (inverse variance). The pooled confidence interval is corrected for multiplicity between the 2 a priori endpoints.

Fig 2

Fig 2A: Forest Plots of Unadjusted Correlation between Perceived Stress and Telomere Length Fig 2B: Forest Plot of Age-Adjusted Correlation between Perceived Stress and Telomere Length n.p. = not published. Fig 2A displays the unadjusted correlation. Fig 2B displays the age-adjusted correlation. Studies are displayed in descending order of weight (inverse variance). The pooled confidence interval is corrected for multiplicity between the 2 a priori endpoints.

Figure 3. Pooled Point Estimates from A Priori, Subset, and Moderation Analyses

For consistency, estimates from meta-regressive models are presented as fitted values rather than coefficients and represent the estimated PS-TL correlation for the relevant group. Thus, plotted confidence intervals correspond to testing for a nonzero correlation within the group of interest rather than a comparison of effect sizes across groups. Bracketed p-values correspond to meta-regressive tests of differences across groups.