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.

Mindfulness‐based cancer recovery and supportive‐expressive therapy maintain telomere length relative to controls in distressed breast cancer survivors

“…Given the increasingly well-documented association between TL and cancer initiation 46 and survival, 47 this finding adds to the literature supporting the potential for stress-reducing interventions to impact important disease-regulating processes and ultimately disease outcome. 48 Inconsistent with other findings, 23,28 we did not observe any associations between changes in stress or mood scores over the course of the interventions and concomitant changes in TL. This could be due to the short time span of the interventions, and the use of different measures of stress and mood than previous researchers, in a different population (patients with breast cancer vs cervical cancer 23 and healthy individuals 28 ).…”

“…48 Inconsistent with other findings, 23,28 we did not observe any associations between changes in stress or mood scores over the course of the interventions and concomitant changes in TL. This could be due to the short time span of the interventions, and the use of different measures of stress and mood than previous researchers, in a different population (patients with breast cancer vs cervical cancer 23 and healthy individuals 28 ).…”

“…20,22 Telomere biology represents another provocative potential pathway that may link psychosocial influences with cancer progression. 23 One report of associations between decreases in distress levels and increased TL over a 4-month period in survivors of cervical cancer is to our knowledge the only current evidence of associations between TL and stress in individuals with cancer. 23 Intervention studies have now examined the effects of psychosocial programs on telomerase activity and TL.…”

“…23 One report of associations between decreases in distress levels and increased TL over a 4-month period in survivors of cervical cancer is to our knowledge the only current evidence of associations between TL and stress in individuals with cancer. 23 Intervention studies have now examined the effects of psychosocial programs on telomerase activity and TL. An uncontrolled study by Ornish et al reported lifestyle changes including a low-fat diet, exercise, and stress reduction in patients with low-risk prostate cancer were significantly associated with increases in telomerase activity, which was significantly associated with decreases in low-density lipoprotein, cholesterol, and psychological distress.…”

Looking Forward to 2013—Saluting the Exceptional Year in 2012

“…In the October 2012 issue of the journal, the Edward Nelson group reported their provocative study within a randomized clinical trial showing that interventions reducing psychosocial distress can lengthen telomeres in peripheral blood mononuclear cells; longer telomere length has been associated in other studies with younger age and reduced heart disease and cancer (23). This new study builds on exciting work of Nobel Laureate Elizabeth Blackburn and Elisa Epel that is summarized in a related Minireview in the same issue of the journal (24).…”