Subjects: Japanese population, glucocorticoid receptor, fear conditioning, cortical thickness, childhood maltreatment, youth, interleukin-6, mismatch hypothesis, prospective cohort, longitudinal course, retrieval, capsaicin, animal model, early life stress, trauma, brain development, genes, adolescents, social behavior, pregnancy, neuropeptide Y, Prenatal stress, mRNA, vulnerability, avoidance, mineralocorticoid, CRHR1, cortisol, CRHR2, safety learning, glucocorticoid regulation synaptic plasticity, IL-6, gene expression, hormone levels, dose–response, treatment, cumulative stress exposure, trait negative affect, sleep, teleomere biology, stress response, cardiovascular risk, Cushing syndrome, sensitization, resilience, novel treatments, resiliency, anxiety disorders, prognosis, ADHD, context processing, major depressive disorder, prospective study, mortality, aging, immunoprotection, glucocorticoid regulation, communion, military, emotional memories, FKBP-5, stress inoculation, reconsolidation blockade, HPA axis, child abuse, traumatization, cognitive disorder, depressive, systemic drugs, corticotropin-releasing factor (CRF), stress regulation, substance use, anxiety, monkeys, chronic inflammatory disease, metastatic breast cancer, 48 IU, memory, PTSD, methlylation, psychotic depression, learning, mice, amniotic fluid, declarative memory, CRF-R1, Fatty acid amide hydrolase, animal study, psychobiological stress reactivity, neurobiology, morbidity, pre-pulse inhibition, intranasal oxytocin, MHPG, pain, genetic model, C-reactive protein, immune cells, newborn, salivary cortisone, 2-arachidonoylglycerol, DNA methylation, maternal life course history, classical conditioning, early life separation, HPA-axis, diurnal rhythm, cancer, endocannabinoids, positron emission tomography, GR antagonists, lipids, salivary cortisol, mifepristone, FKBP5, psychophysiological risk, fMRI, cortisol/cortisone ratio, primate, 24 IU, autobiographical memory, emotional memory, children, TSST, cytokines, gestational weight, progesterone blockade, social bonding, social support, oxytocin, behavioral adaptation, Gulf War veterans, suicide, leptin, posttraumatic stress disorder, early life trauma, early psychosis, CB1 receptor, post-traumatic stress disorder, traumatic stress, gender, exercise, gene environment interaction, trauma susceptibility, BclI, BDNF, inflammation, chronic multisymptom illness, dose-response, placental CRH, violence, stress, PTSD, socioeconomic position, agency, early programming, oxidation, health, birthweight, transgenerational effects, emotion, signaling pathways, SNP, temperament, early adversity, stressful life events, BMI, executive function, cortisone, fear extinction, teleomere erosion, Supplement 1, 2012, cognitive testing, childhood trauma, glucocorticoid receptors, obesity, brain imaging, survival, patients, exposure therapy, MDD, biomarker, maternal care, startle, childhood stress, arthritis, methylation, metabolism, panic disorder, endocannabinoid, veterans, susceptibility, teleomere length, memory consolidation, prefrontal cortex, hair, attachment, CRH, glucocorticoids, dexamethasone, autoimmune disorders, corticotropin-releasing hormone, Glucocorticoid, cognition, hippocampus, allostatic load, therapy, saliva, fear responses, anadamide, depression, cumulative stress, prolonged exposure, CB2 receptor, psychiatric disorders
Rationale/statement of the problem Chronic stressors across the life course predict accelerated pathogenesis of diseases of aging and early mortality. Telomere length, the DNA-based biomarker indicating cellular aging, is a mechanism of disease development, and shortens in a dose response fashion by duration and severity of life stressor exposures. Telomere length provides an important window in understanding a life span model of the accumulation of stress on aging. Self-reported perceived chronic stress and exposure to stressful life experiences during childhood and adulthood are related to short telomeres. While the expectation that the accumulation of life stress leads to cellular senescence, most studies indicate cross-sectional associations between life stressors and telomere length. Findings suggesting longitudinal associations between life stressors and telomere shortening are best represented in studies associating self-reported early childhood traumatic experiences with short telomeres in adulthood. Adults reporting moderate-to-severe childhood maltreatment and stressful experiences, such as divorce and parental separation, are more likely to have significantly shorter telomeres than those reporting no childhood maltreatment. To date, only one study has prospectively demonstrated associations between traumatic experiences and telomere shortening. Five-year-old children exposed to two or more traumatic stressors, including maternal domestic violence, frequent bullying victimization and physical maltreatment by an adult, have shorter telomeres at age 10 compared with children exposed to less or no violent stressors. No studies, however, indicate prospective effects of adulthood stressors on telomere shortening over time. Perhaps, as we suggest elsewhere, chronic stressor effects on biological pathways are rarely main effects, but rather an intricate interplay between life adversity and resiliency factors. Our work, and that of others, is increasing our understanding of how psychological stress resilience, social connections, and lifestyle may moderate relationships between life stressors and health. Here, we present evidence from two studies that support our proposed model that behavioral and psychosocial resiliency can buffer the effects of stress on telomere length, both cross-sectionally and prospectively. Cross-sectionally, we tested whether multisystem resiliency – defined as a composite of healthy emotion regulation, strong social connections, and being physically active – mitigates previously demonstrated associations between concurrent depression diagnosis and telomere length. We found support for this model, which will be presented. In a second study we examined how a lifestyle composite might buffer stress-induced telomere shortening prospectively. Methods Two hundred sixty-one non-smoking women between the ages of 50 and 65 were recruited for a prospective study on telomere length change over the course of the year. Leukocyte telomere length (LTL) was assayed at baseline and 12-month follow-up. Perceived stress, typical dietary practices, sleep quality, and exercise levels were self-reported at baseline, 4 months, 8 months, and 12 month follow-up. Seventeen questions about life events that may have occurred in the previous year were asked at follow-up, including events such as divorce, death of a family member, and job loss. Health events were not included as they may confound effects of stressors on telomere biology. Women with histories of cancer, who were premenopausal, or did not have complete self-report data were excluded from these analyses, leaving a final sample of 196 women. Results Results indicated that perceived stress at baseline, perceived stress accumulated over the year, or accumulation of stressors over the year were unrelated to 12-month LTL, covarying baseline telomere length, age, BMI, and income level. However, findings do suggest significant interactions between markers of stress and a healthy lifestyle over the year composed of healthy dietary practices, sleep quality, and exercising. For those at one standard deviation below mean healthy lifestyle, baseline perceived stress (b=−8.51, SE=4.05, p=.04) and accumulation of life stressors over the year (b=−34.51, SE=15.21, p=.02), were significantly associated with shorter LTL at follow-up, covarying baseline telomere length, age, BMI, and income level. On the contrary, at one standard deviation above the mean of healthy lifestyle, stress markers were unrelated to telomere shortening over the year. Conclusion In summary, healthy lifestyle factors and psychosocial resiliency may interrupt a cascade of harmful effects that accelerate cellular aging, diminishing the impact that chronic psychological or objective life stress has on health. From conception to death, we are exposed to stressors. And while stressors may shape the manifestation of resiliency factors, leading to an interrelated cluster, our work suggests that psychosocial resources and lifestyle factors can add up to multisystem resiliency, providing increasing cellular buffering from life stress. Without attending to such interactions, stress effects are often masked and missed.