Understanding factors influencing the aging process is central to reducing morbidity, an increasingly important goal in light of our rapidly aging population. Psychological stress is thought to accelerate biological aging. We found support for this hypothesis using the telomere length/telomerase maintenance system as an index of cell aging in vivo. Leukocyte telomere length (TL), the length of the DNA caps at the ends of chromosomes, shortens with age and predicts mortality. Telomerase is the cellular enzyme that lengthens and protects telomeres. Our preliminary data suggest that chronic psychological stress is associated with cell aging (PBMC TL shortening and decreases in telomerase activity) in two samples of caregivers, and further, prospective increases in stress are associated with decreases in TL over just one year. In vitro research has shown that TL is shortened most in specific cytolytic cells (CD8+CD28- T cells), especially from older donors, which is significant in that CD8+CD28- T cells secrete more proinflammatory cytokines and are a hallmark of immunosenescence. Thus, we will examine prospectively whether chronic stress precedes decreases in telomerase and TL in these cells, as well as in peripheral blood mononuclear cells (PBMCs), in older women. We will investigate putative biochemical mediators of this relationship, focusing on stress hormones and insulin resistance. In our pilot study, we also found that acute psychological stress, in contrast to chronic stress, is associated with acute increases in PBMC telomerase activity (""""""""telomerase reactivity""""""""). The magnitude of this increase was greater in caregivers than in controls. These are novel findings requiring replication with a larger sample. They raise the possibility that exaggerated initial telomerase responses to acute stress may signal unsuccessful attempts at telomere maintenance in chronically stressed individuals. To accomplish these aims, we will examine cell aging in a sample of 150 healthy postmenopausal women, aged 50-75, comparing chronically stressed caregivers (n = 75), to low stress controls (n = 75), matched on age, body fat, ethnicity, and education. We will test for stress-related differences in telomerase and TL in PBMCs, CD8 T cells (CD28+ and CD28-), CD4 T cells, and B cells, at baseline and 2 years later (Aim 1). Secondly, we will examine whether telomerase reactivity after acute lab stress predicts changes in TL over 2 years (Aim 2). Lastly, we will test in vitro whether T cells from high stress caregivers have impaired functional immune responses (greater proinflammatory cytokine response to stimulation, impaired cytotoxic function), and if these differences are mediated by lower basal telomerase and shorter telomeres (Aim 3). Together, these aims will provide a clearer picture of stress-induced immune senescence, elucidating the roles of telomeres and telomerase. Since shorter telomeres predict future disease and earlier mortality, understanding the risk factors for accelerated telomere shortening may facilitate interventions aimed at forestalling such outcomes.

Public Health Relevance

Psychological stress increases risk of disease, and this study examines a potential biological pathway to help explain how. Shorter telomere length (the protective caps at the end of chromosomes) in immune cells, a marker of cell aging, predicts disease and early death. This study tests whether chronic stress accelerates immune cell telomere shortening, and the potential intermediate mechanisms, and could lead to biological targets for protective psychological or pharmacological interventions to mitigate the health risks associated with stress.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Spotts, Erica L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code
Mason, Ashley E; Schleicher, Samantha; Coccia, Michael et al. (2018) Chronic Stress and Impulsive Risk-Taking Predict Increases in Visceral Fat over 18 Months. Obesity (Silver Spring) 26:869-876
Da Paz, Nikko S; Siegel, Bryna; Coccia, Michael A et al. (2018) Acceptance or Despair? Maternal Adjustment to Having a Child Diagnosed with Autism. J Autism Dev Disord 48:1971-1981
Felder, Jennifer N; Epel, Elissa S; Coccia, Michael et al. (2018) Effects of daily maladaptive coping on nightly sleep in mothers. Psychol Health 33:144-157
Mason, Ashley E; Adler, Jonathan M; Puterman, Eli et al. (2018) Stress resilience: Narrative identity may buffer the longitudinal effects of chronic caregiving stress on mental health and telomere shortening. Brain Behav Immun :
Picard, Martin; Prather, Aric A; Puterman, Eli et al. (2018) A Mitochondrial Health Index Sensitive to Mood and Caregiving Stress. Biol Psychiatry 84:9-17
Prather, Aric A; Epel, Elissa S; Portela Parra, Eduardo et al. (2018) Associations between chronic caregiving stress and T cell markers implicated in immunosenescence. Brain Behav Immun 73:546-549
Cabeza de Baca, Tomás; Epel, Elissa S; Robles, Theodore F et al. (2017) Sexual intimacy in couples is associated with longer telomere length. Psychoneuroendocrinology 81:46-51
Aschbacher, Kirstin; Milush, Jeffrey M; Gilbert, Amanda et al. (2017) Chronic stress is associated with reduced circulating hematopoietic progenitor cell number: A maternal caregiving model. Brain Behav Immun 59:245-252
Hagan, Melissa J; Bush, Nicole; Mendes, Wendy Berry et al. (2017) Associations between childhood adversity and daily suppression and avoidance in response to stress in adulthood: can neurobiological sensitivity help explain this relationship? Anxiety Stress Coping 30:163-175
Catalino, Lahnna I; Arenander, Justine; Epel, Elissa et al. (2017) Trait acceptance predicts fewer daily negative emotions through less stressor-related rumination. Emotion 17:1181-1186

Showing the most recent 10 out of 24 publications