Accelerated telomere shortening in response to life stress

Abstract

Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets "under the skin" remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress--both perceived stress and chronicity of stress--is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. 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.

Fig. 1.

Scatter plots of chronicity of stress by telomere length in caregivers and perceived stress scores by telomere length. (A) The zero-order correlation between chronicity of caregiving and mean telomere length, r,is –0.445 (P <0.01) and, adjusting for the mother's age, it remains significant (r =–0.40, P <0.01). To test whether the age of the child accounts for this relationship independently of caregiving, correlations between the age of the child and the mean telomere length were calculated in each group. The age of the child is related to shorter telomeres in the caregiver group (r =–0.45, P < 0.01) but not the control group (r = +0.22, P value not significant). These findings demonstrate that the relationship between chronicity of caregiving and mean telomere length is not simply due to either the mother's or child's older age. (B) Zero-order correlation across the sample is r = –0.31 (P < 0.01, n = 57). When the correlation is adjusted for age, BMI, smoking, and vitamin use, the correlation remained significant (r =–0.27, P < 0.05). In both the control (blue diamond) and high-stress (red circle) groups, the higher the stress level ranking, the lower the telomere length (controls, r =–0.34; caregivers, r =–0.36; adjusted for age). When the one particularly high-stress control subject is eliminated, there is still an association among the lower stress controls, showing that those with the lowest stress have the longest mean telomere length (r = –0.27).

Fig. 2.

Telomere length and telomerase activity levels in extreme high- and low-stress groups. (A) Average telomere length and SE are shown. The high-stress group had shorter telomeres even after controlling for age and BMI [F(1, 27) = 12.8, P < 0.001]. (B) Average telomerase activity and SE are shown. The high-stress group had lower telomerase activity even after controlling for age and BMI [F(1, 27) = 3.1, P < 0.05]. Because values for telomerase activity were not normally distributed, the values were converted to follow a normal distribution by using a natural logarithm transformation. All statistical analyses were performed on the transformed variable. The raw (unadjusted) levels of telomerase are presented throughout because these values are more meaningful than transformed values.