Longitudinal change in telomere length and the chronic stress response in a randomized pilot biobehavioral clinical study: implications for cancer prevention

Abstract

Shortened telomere length is associated with increased cancer incidence and mortality. Populations experiencing chronic stress have accelerated telomere shortening. In this exploratory study, we examined associations between longitudinal changes in patient reported outcomes (PRO) of psychologic distress and peripheral blood mononuclear cell (PBMC) telomere length to test the hypothesis that modulation of the chronic stress response would also modulate telomere dynamics. Archived PBMC specimens (N = 22) were analyzed from a completed and reported randomized, longitudinal trial that showed a psychosocial telephone counseling intervention improved quality of life (QOL) and modulated stress-associated biomarkers in cervical cancer survivors. PROs and biospecimens were collected at baseline and 4 months postenrollment. Telomere length of archived PBMCs was evaluated using the flow-FISH assay. Longitudinal changes in psychologic distress, measured by the Brief Symptom Inventory-18, were significantly associated with increased telomere length within the CD14(+) (monocyte) population (r = -0.46, P = 0.043); a similar trend was observed for the CD14(-) population. Longitudinal changes in telomere length of the CD14(-) subset, primarily T lymphocytes, were associated with longitudinal increases in the naive T-cell population (r = 0.49, P = 0.052). Alterations in the chronic stress response were associated with modulation of telomere length in PBMCs, with evidence for mobilization of "younger" cells from progenitor populations. These data provide preliminary support for the (i) capacity to modulate the chronic stress response and the associated accelerated telomere shortening, (ii) inclusion of telomere length in the biobehavioral paradigm, and (iii) potential link between the chronic stress response and biologic mechanisms responsible for genomic integrity and carcinogenesis.

Figures

Figure 1

Longitudinal association of chronic stress response and QOL. Correlation plot of association between longitudinal changes in BSI-18 global scores and FACT-Cx scores (N = 22), showing that decreased distress (an improved stress response) is associated with improved QOL. Data points reflect longitudinal change from baseline to T2, Pearson correlation coefficient, r = −0.47, P = 0.032, 2-sided analysis; plot features least-squares regression line.

Figure 2

Longitudinal change in telomere length MFI index of CD14+ and CD14− subsets. Data points were obtained from subtracting the baseline telomere length MFI index from the T2 telomere length MFI index of CD14+ and CD14− subsets.

Figure 3

Baseline and longitudinal change in telomere length are associated in CD14+ and CD14− subsets. A, correlation plot of baseline and longitudinal change in telomere length MFI Index of CD14+ subsets (N = 22), showing that shorter telomeres at baseline were more likely to increase at T2, Pearson correlation coefficient, r = −0.62, P = 0.003, 2-sided analysis; plot features least-squares regression line. B, correlation plot of baseline and longitudinal change in telomere length MFI index of CD14− subsets (N = 22), showing that shorter telomeres at baseline were more likely to increase at T2, Pearson correlation coefficient, r = −0.85, P < 0.001, 2-sided analysis; plot features least-squares regression line.

Figure 4

Longitudinal association of chronic stress response and telomere index of CD14+ and CD14− subsets. A, correlation plot of longitudinal changes in BSI-18 global raw scores and telomere length MFI index of CD14+ subsets (N = 22), showing that decreased distress was associated with increased telomere length. Data points reflect longitudinal change from baseline to T2, Pearson correlation coefficient, r = −0.46, P 0.043, 2-sided analysis; plot features least-squares regression line. B, correlation plot of longitudinal changes in BSI-18 global raw scores and telomere length MFI index of CD14− subsets (N = 22), showing that decreased distress was associated with increased telomere length. Data points reflect longitudinal change from baseline to T2, Pearson correlation coefficient, r = 0.36, P = 0.1, 2-sided analysis; plot features least-squares regression line. These analyses were controlled for age and baseline telomere length.

Figure 5

Longitudinal association of telomere index of CD14+ and CD14− subsets and percentage change in CD45RA+ naive T cells. A, correlation plot of longitudinal changes in telomere length MFI Index of CD14+ subsets and percentage change of CD45RA+ naive T cells (N = 17), showing that increased telomere length in CD14+ subsets was not associated with increased percentage of CD45RA+ naive T cells. Data points reflect longitudinal change from baseline to T2, Pearson correlation coefficient, r = 0.09, P = 0.731, 2-sided analysis; plot features least-squares regression line. B, plot of longitudinal changes in telomere length correlation MFI index of CD14− subsets and percentage change of CD45RA+ naive T cells (N = 17), showing that increased telomere length in CD14− subsets was associated with increased percentage of CD45RA+ naive T cells. Data points reflect longitudinal change from baseline to T2, Pearson correlation coefficient, r = 0.49, P = 0.052, 2-sided analysis; plot features least-squares regression line. These analyses were controlled for age and baseline telomere length.

Figure 6

Baseline telomere length of CD14+ and CD14− subsets and longitudinal percentage change in CD45RA+ naive T cells. A, correlation plot of baseline telomere index of CD14+ subsets and longitudinal percentage change in CD45RA+ naive T cells (N = 17), showing that telomere length of CD14+ subsets at baseline were not associated with percentage of CD45RA+ naive T cells at T2. Pearson correlation coefficient, r = 0.07, P = 0.811, 2-sided analysis; plot features least-squares regression line. B, correlation plot of baseline telomere index of CD14− subsets and longitudinal percentage change in CD45RA+ naive T cells (N = 17), showing that shorter telomere length of CD14− subsets at baseline was associated with a larger percentage of CD45RA+ naive T cells at T2. Pearson correlation coefficient, r = −0.44, P = 0.088, 2-sided analysis; plot features least-squares regression line.