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Stressful experiences have long been considered risk factors for early onset of age-related disease and premature death, yet scientific research on the contribution of social life stress and discrimination to the development of accelerated immune aging is limited. Some recent findings, however, may have important implications for healthy longevity.

Published in PNAS, a new study assesses the association between social stress and immunophenotypes for the first time in a national sample of older adults.¹ In the study, Klopack et al analyzed data from 5,744 adults over the age of 50 who had answered questions about stress and provided blood samples as part of the Health and Retirement Study—a large, nationally representative study of Americans aged 50 and older. Their goal was to determine the link between T cell populations and five categories of stressors: everyday discrimination, stressful life events, lifetime discrimination, life trauma, and chronic social stress. They found that exposure to social stress and discrimination was associated with T cell distributions indicative of accelerated immune aging.¹

Specifically, the researchers evaluated the percentages of both CD4+ cells, which aid in directing immune responses, and CD8+ T cells, which attack pathogens.¹ Specifically, life trauma and chronic stress were associated with a lower percentage of CD4⁺ naïve T cells; accelerated immune age phenotype in CD4⁺ T cells may be particularly indicative of aging immunity. Everyday discrimination, lifetime discrimination, and chronic stress were associated with a greater percentage of terminally differentiated CD8⁺ T cells. This finding is consistent with the possibility that thymic involution may be accelerated by social stress via chronic activation of the hypothalamic-pituitary-adrenal axis, which can accelerate thymic involution and thereby reduce naïve T cell development.¹

Both high lifetime discrimination and chronic stress were also associated with a lower overall ratio of CD4+ cells to CD8+ cells—an indication of immune aging.¹ These effects were all independent of chronological age, sex, and race/ethnicity. Lifetime discrimination and chronic stress were associated with a greater percentage of terminally differentiated CD4+ T cells, regardless of controls. In this study, participants reported facing different types of discrimination, including on the basis of gender and race, but most commonly for their age.¹

Growing evidence suggests that social stress and discrimination is an important stressor associated with psychological distress, chronic low-grade inflammation, and cardiovascular health.² Studies continue to link stress with immune dysregulation and a number of autoimmune and atopic diseases such as inflammatory bowel disease, allergy, atopic dermatitis, and celiac disease.^3,4 Some evidence suggests that stressful events may induce sympathetic nervous system and endocrine changes, among other biological responses, and that these changes can ultimately impair immune function.⁵

Clinical Considerations

Widespread stress is a public health issue that affects underserved populations disproportionately.⁶ Low-income women with histories of trauma are a particularly vulnerable and underserved subgroup, in part due to other cumulative and enduring life stressors such as poverty and racial discrimination, which often compound the psychological and physiological burden of traumatic experiences.⁷ However, many modifiable lifestyle factors that ameliorate stress are easily accessible, including dietary patterns focused on anti-inflammatory foods that may contribute to a more robust immune system through reducing inflammation and oxidative stress.^8,9 Accessibility and consumption of varied and healthy foods also influences gut microbiome function, a key regulator of immune system homeostasis.

As well, a variety of other lifestyle-based treatments have the potential to improve the stress response by inducing relaxation (a state of decreased sympathetic nervous system activity that opposes the stress response), including meditation, yoga, progressive muscle relaxation, guided imagery, and biofeedback.¹⁰ Mindfulness-based stress reduction or mindfulness-based cognitive therapy may also be beneficial; studies suggest decreased anxiety, improved mood, relief of psychological distress, and strengthened well-being.¹⁰

Meeting a patient where they are and recognizing the social conditions that contribute to their stress are important parts of a patient-empowered collaborative relationship. These considerations help to provide the most effective personalized interventions that support optimal immune health. By learning to identify stressors like discrimination and address the underlying causes of stress, you’ll not only help your patients return to health but also teach them how to modify their lifestyle when times of anxiety resurface.

References

1. Klopack ET, Crimmins EM, Cole SW, Seeman TE, Carrol JE. Social stressors associated with age-related T lymphocyte percentages in older US adults: evidence from the US Health and Retirement Study. Proc Natl Acad Sci U S A. 2022;119(25):e2202780119. doi:1073/pnas.2202780119
2. Saban KL, Mathews HL, Bryant FB, et al. Perceived discrimination is associated with the inflammatory response to acute laboratory stress in women at risk for cardiovascular disease. Brain Behav Immun. 2018;73:625-632. doi:1016/j.bbi.2018.07.010
3. Carlsson E, Frostell A, Ludvigsson J, Faresjö M. Psychological stress in children may alter the immune response. J Immunol.2014;192(5):2071-2081. doi:4049/jimmunol.1301713
4. Morey JN, Boggero IA, Scott AB, Segerstrom SC. Current directions in stress and human immune function. Curr Opin Psychol. 2015;5:13-17. doi:1016/j.copsyc.2015.03.007
5. Tizenberg BN, Brenner LA, Lowry CA, et al. Biological and psychological factors determining neuropsychiatric outcomes in COVID-19. Curr Psychiatry Rep. 2021;23(10):68. doi:1007/s11920-021-01275-3
6. Gallup 2019 Global Emotions Report. Published 2019. Accessed July 19, 2022. https://www.gallup.com/analytics/248906/gallup-global-emotions-report-2019.aspx
7. Dutton MA, Bermudez D, Matas A, Majid H, Myers NL. Mindfulness-based stress reduction for low-income, predominantly African American women with PTSD and a history of intimate partner violence. Cogn Behav Pract. 2013;20(1):23-32. doi:1016/j.cbpra.2011.08.003
8. Iddir M, Brito A, Dingeo G, et al. Strengthening the immune system and reducing inflammation and oxidative stress through diet and nutrition: considerations during the COVID-19 crisis. Nutrients. 2020;12(6):1562. doi:3390/nu12061562
9. Childs CE, Calder PC, Miles EA. Diet and immune function. Nutrients. 2019;11(8):1933. doi:3390/nu11081933
10.  Franke HA. Toxic stress: effects, prevention, and treatment. Children (Basel). 2014;1(3):390-402. doi:3390/children1030390