It is common knowledge in our increasingly fast-paced and stressful society that chronic stress is injurious to a person’s health, but how our psychological stress really translates into physiological consequences is still a growing area of research. The study “Does cellular aging relate to patterns of allostasis? An examination of basal and stress reactive HPA axis activity and telomere length”, published in Physiology and Behavior, explores the link between psychology and biology by studying how the psychological stress that a person experiences relates to the shortening of telomeres .
Telomeres are DNA-protein complexes that serve as protective caps at the ends of an organism’s chromosomes. Every time a cell divides by mitosis, its DNA gets shorter and shorter at its ends. This occurs because short RNA molecules that assist in the replication of DNA bind to the ends of the DNA, so that the ends are prevented from being replicated . Telomeres located at the ends of chromosomes thus degrade instead of the crucial genes on the DNA strands. When telomeres become too short, the cell can no longer divide and becomes inactive or dies. In this way, telomere length is both a marker and a mechanism of aging; it serves as a clock for a cell’s lifespan and, when shortened, is associated with cellular aging, cancer, heart disease, as well as infectious diseases .
These deleterious effects on telomeres can be slowed down or reversed by a person’s lifestyle choices. Exercising, a healthy diet, and reducing psychological stress all protect a person from telomere shortening . Furthermore, cells also contain a crucial enzyme called telomerase, which maintains and protects telomeres from eroding. In addition to its protective effects, telomerase can also elongate telomeric DNA to counteract the shortening of telomeres .
When a person experiences psychological stress, the hypothalamic-pituitary-adrenocortical (HPA) axis of their brain is activated. The HPA axis produces cortisol, which is released into the blood. The quantity of cortisol that is secreted is used as an indicator of stress reactivity, with higher stress reactivity indicated by higher levels of salivary cortisol. Studies have found that high cortisol levels lower the amount of telomerase in cells. It also reduces the maintenance of telomeres, suggesting a correlation between stress and shorter telomere length .
This study uses telomere length as a representation of allostatic load. Allostatic load is the wear and tear on a person’s body that grows when an individual is exposed to chronic stress. The “allostatic load model” that is described in this research is the idea that many patterns of altered responses to stress (HPA axis dysregulation) contribute to allostatic load. The researchers hypothesize that chronic stress may influence the regulation of the HPA axis, affecting levels of cortisol secretions, contributing to allostatic load and leading to impaired telomere maintenance .
The study recruited 23 post-menopausal women, 14 of whom were caregivers for dementia partners, and 9 of who were not caregivers but who were of similar age and body mass index (BMI). The researchers first isolated subjects’ peripheral blood mononuclear cells (PBMCs) in order to measure their telomere lengths. For the next three days, the participants were instructed to provide three saliva samples per day at waking, 30 minutes after waking, and at bedtime, which were used measure the amount of cortisol secreted and quantify their diurnal cortisol rhythm. The participants also provided a 12 hour overnight urine sample on the last night of saliva sampling. A week later, they completed the laboratory stress session, where they were subjected to the modified Trier Social Stress Test that would elicit psychological stress and cortisol responses. Several saliva samples were taken throughout this session.
In examining the results of the study, the researchers observed the relationship between telomere length and the following factors: cortisol response to acute stress, diurnal cortisol slope, cortisol awakening response, and nocturnal free cortisol. The cortisol response to acute stress was measured by salivary cortisol levels after the subjects were exposed to the Trier Social Stress Test. The researchers found that greater cortisol response to acute stress was related to shorter telomeres after controlling for age, BMI, and caregiver status . The researchers also measured diurnal cortisol slopes. Normal slopes depict steadily decreasing levels of cortisol throughout the day (cortisol levels are normally highest in the morning and the lowest between midnight and 4 a.m.). The researchers discovered that flatter diurnal cortisol slopes were associated with shorter telomere length, suggesting that flatter diurnal cortisol slopes–where cortisol levels decrease less throughout the day–may be a sign of expedited cellular aging .
The researchers also measured cortisol awakening response by subtracting the wakeup cortisol value from the wakeup value at 30 minutes after waking. Their results demonstrated that the cortisol awakening response was not associated with telomere length. On the other hand, when they measured nocturnal free cortisol levels from 12 hour overnight samples, they observed that greater total overnight free cortisol levels were associated with shorter telomere length. Overnight cortisol indicates how well one’s system can regulate and recover from the demands of the day. In normal functioning, limbic-hippocampal and other neural networks inhibit the release of cortisol nocturnally, but immediately after acute stress and in those who experience chronic stress, there is a lack of cortisol inhibition. The results from the participants demonstrated that cortisol levels did not decrease at night, as they do in normal individuals .
Through these experiments, the researchers concluded that there are strong correlations between levels of cortisol and shortened telomere length, showing an important link between stress and early aging . These results are consistent with the growing number of studies on telomeres, a few of which have found shortening telomere length present even in children. A study published a year later in Molecular Psychiatry compared children who grew up in a Romanian orphanage with children who were placed in foster homes; overall, they found that children who spent a longer time in institutionalized care had significantly shorter telomere length by middle childhood than children who were in foster care . In addition, a study published in 2010 found that adults who experienced childhood stress had shorter telomeres as well .
This research gives an explanation for a pervasive phenomenon in our everyday lives: how busy, stressful lives compromise our health and wellbeing. Through telomere shortening, stress can indeed write itself onto one’s genetic code and lead to disease and health problems in the future, further underscoring the importance of managing stress in one’s everyday life.
References: AJ Tomiyama, A O’Donovan, J Lin, E Puterman, A Lazaro, J Chan, FS Dhabhar, O Wolkowitz, C Kirschbaum, E Blackburn, E Epel. 2012. “Does cellular aging relate to patterns of allostasis? An examination of basal and stress reactive HPA axis activity and telomere length.” Physiology & Behavior 106(1):40-5.  Lee J. Siegel, “Are Telomeres the Key to Aging and Cancer?” University of Utah Health Sciences. Accessed December 9, 2013. http://learn.genetics.utah.edu/content/chromosomes/telomeres  Elizabeth Fernandez. “Lifestyle Changes May Lengthen Telomeres, A Measure of Cell Aging,” UCSF News. Accessed May 9, 2014. https://www.ucsf.edu/news/2013/09/108886/lifestyle-changes-may-lengthen-telomeres-measure-cell-aging  SS Drury, K Theall, MM Gleason, AT Smyke, I De Vivo, JY Wong, NA Fox, CH Zeanah, CA Nelson. 2012. “Telomere length and early severe social deprivation: linking early adversity and cellular aging.” Molecular Psychiatry 17(7): 719-727  L Kananen, I Surakka, S Pirkola, J Suvisaari, J Lönnqvist, L Peltonen, S Ripatti, I Hovatta. 2010. “Childhood Adversities Are Associated with Shorter Telomere Length at Adult Age both in Individuals with an Anxiety Disorder and Controls.” PLoS ONE 5(5): e10826.
Image References: Retrieved December 9, 2013 from: Wikipedia. http://upload.wikimedia.org/wikipedia/commons/6/6a/Telomere.png  Forrest Tennant. “How to Use Adrenocorticotropin as a Biomarker in Pain Management.” 2012. Practical Pain Management. Accessed December 22, 2014. http://www.practicalpainmanagement.com/resources/diagnostic-tests/how-use-adrenocorticotropin-biomarker-pain-management
Srividya Murthy is a junior at George Washington University majoring in Biophysics and minoring in Journalism and Mass Communication. Follow The Triple Helix Online on Twitter and join us on Facebook.