Research Paper
The Effects of Stress on Cellular Aging
While growing older is an unavoidable element of life, lifestyle has long been a contributing factor to the rate at which humans age. Although stress, in particular, is aging humans at an alarming rate, all the way down to the cellular level, it may be possible to slow the process through lifestyle changes.
Gerontologists at the National Institute on Aging (NIA), a division of the National Institute of Health (NIH), have been studying the process of aging since the NIA’s inception in 1974 (Biology of Aging, 2011). Examining the contributing factors that lead to the physical decline of humans, Gerontologists have brought the study down to the cellular level, where they seek to identify the effects of lifestyle and disease from the normal effects of the aging process (Biology of Aging, 2011).
The human genome is comprised of roughly 25,000 genes, which are composed of approximately 3 billion base pairs of DNA; over time, although DNA is equipped to repair damage, some damaged genetic material will cease to repair and remains within the genetic code (Biology of Aging, 2011). Scientists believe that this inability for the body to continue to repair sustained damage is a critical element of the aging process (Biology of Aging, 2011).
The telomere, from the Greek words telos, or “end” and meros, or “part,” is the protective cap of approximately 2000 repeating nucleotide sequences of TTAGGG located at the ends of chromosomes (Zhang, Hu, Li, X., Li, H., Smerin, Russell, and Ursano, 2014). Scientist Barbara McClintock discovered that without these structures, chromosomes would fuse, degrade, or recombine during mitosis and lead to chromosomal instability (Zhang et al., 2014). Over time, after each cellular division, the telomere shortens, unless counteracted by telomerase, the cellular enzyme responsible for adding telomeric DNA to the ends of the telomere (Epel et al. 2004).
In the absence of telomerase activity, as a result of the shortening, the cell will either enter senescence, or stop replicating; suffer apoptosis, or cell death; or continue to divide without protection, which can lead to potentially dangerous abnormalities (Biology of Aging, 2011). According to Harvard’s Masood Shammas (2011) “telomere length may therefore serve as a biological clock to determine the lifespan of a cell and an organism.”
In the human population, telomeres shorten at a rate of 24.8-27.7 base pairs per year, with studies showing that a “shorter than average telomere length for a specific age group, has been associated with increased incidence of age-related diseases and/or decreased life span” (Shammas, 2011). Along with age-related health conditions such as cardiovascular disease, diabetes, cancer and osteoporosis, elderly humans with shorter telomeres have a higher mortality rate that that of their peers with longer telomeres (Shammas, 2011). According to Shammas (2011), stress also increases the rate of telomere shortening. Glucocorticoid hormones released by the adrenal glands during periods of stress are known to reduce the amounts of antioxidant proteins and can increase oxidative damage to DNA, which can accelerate telomere shortening (Shammas, 2011).
While countless studies have shown a link between stress and poor health, a 2004 study conducted by Epel, Blackburn, Lin, Dhabhar, Adler, Morrow and Cawthon sought to find a direct link between stress and cellular aging. The study examined 58 healthy women, 19 of which served as the control group and were biological mothers of a healthy child; 39 were biological mothers of a chronically ill child, known as “caregivers” (Epel et al., 2004). Mean telomere length and telomerase activity were measured in the samples (Epel et al., 2004). The results of the study found that within the caregiver group, “the more years of caregiving, the shorter the mother’s telomeric length, the lower the telomerase activity, and the greater the oxidative stress, even after controlling for the mother’s age” (Epel et al., 2004). Citing the 2004 study by Epel et al., Shammas (2010) purported that “the difference in telomere length in [the] two groups of women was [the] equivalent to 10 years of life, indicating that the women under stress were at a risk for early onset of age-related health problems.”
A 2011 study by Entringer, Epel, Kumsta, Lin, Hellhammer, Blackburn, Wüst and Wadhwa further established that exposure to intrauterine stress was linked to shorter telomere length in adulthood. Noting that animal studies have reported intrauterine stressors as a contributing factor to shorter telomere length in a variety of tissues, Entringer et al. (2011) state that among preschool-age children, those who were born low birth weight had shorter leukocyte telomere length (LTL) than children of normal birth weight of the same age. In their study, Entringer et al. (2011) observed young adults whose mothers experienced high stress, or a negative life event, during pregnancy with young adults whose mothers did not experience any negative life events during pregnancy. The findings showed the LTL of adults in the stress group was 178 base pairs shorter, on average, than that of the control group (Entringer et al., 2011). This data suggests that the shortage of base pairs translates to the equivalent of 3.5 years of life expectancy relative to the control (Entringer et al., 2011).
Post-traumatic stress disorder (PTSD) is an anxiety disorder that can manifest following exposure to severe traumatic stress (Zhang et al., 2014). PTSD has been found to be associated with “dysregulation of bodily systems that have been linked with biological aging” due to sustained activation of the biological stress response (Zhang et al., 2014). Those suffering from the disorder were observed to have comparatively shorter LTL than that of control subjects (Zhang et al., 2014). A possible explanation for the shortening may lie in inflammation, a byproduct of increased sympathetic nervous system activation, which leads to increased cell turnover; the resulting oxidative stress then damages telomeric DNA and leaves the subject vulnerable to accelerated LTL shortening (Zhang et al., 2014).
Rapid telomere shortening has also been observed among individuals suffering from psychosocial stress and depression; the median telomere length for individuals suffering from long-term depression was 281 base pairs shorter than the control, accounting for 7 years of accelerated cellular aging (Zhang et al., 2014). This finding could also explain the increased morbidity for major depressive orders (MDD), in which “subjects had significantly shortened LTL compared to controls, with an estimated acceleration of biological cell aging of over 10 years” (Zhang et al. 2014).
While chronic stress has been shown to shorten telomere length and accelerate the aging process, a 2010 study by Puterman, Lin, Blackburn, O'Donovan, Adler and Epel maintained that not everyone under stress possessed definitively short telomeres; the findings suggest that the effects of stress can be minimized by physical activity. In contrast to the shortened telomeres of the chronically stressed, physical activity is linked with longer telomeres; the differences were observed in a national sample of identical twins as well as a comparison between athletes and a sedentary population (Puterman et al., 2010). The study found that “above around 40 minutes of vigorous physical activity over 3 days, stress is no longer associated with short telomeres” (Puterman et al., 2010).
The explanation for the benefit of exercise appears to lie with telomerase; physical activity increases telomerase activity, allowing for a slower degradation of the protective ends (Puterman et al., 2010). Puterman et al. (2010) also suggest that “exercise might also buffer telomere shortening through affecting the balance between oxidative stress and antioxidants.”
In conclusion, while science has not yet discovered a “fountain of youth,” or a way to stop the process of aging, scientists have identified significant contributing factors such as stress and exercise, which have the ability to respectively speed up or slow down the rate of aging among a population. The secret to a longer life may literally be a walk in the park. **
Gerontologists at the National Institute on Aging (NIA), a division of the National Institute of Health (NIH), have been studying the process of aging since the NIA’s inception in 1974 (Biology of Aging, 2011). Examining the contributing factors that lead to the physical decline of humans, Gerontologists have brought the study down to the cellular level, where they seek to identify the effects of lifestyle and disease from the normal effects of the aging process (Biology of Aging, 2011).
The human genome is comprised of roughly 25,000 genes, which are composed of approximately 3 billion base pairs of DNA; over time, although DNA is equipped to repair damage, some damaged genetic material will cease to repair and remains within the genetic code (Biology of Aging, 2011). Scientists believe that this inability for the body to continue to repair sustained damage is a critical element of the aging process (Biology of Aging, 2011).
The telomere, from the Greek words telos, or “end” and meros, or “part,” is the protective cap of approximately 2000 repeating nucleotide sequences of TTAGGG located at the ends of chromosomes (Zhang, Hu, Li, X., Li, H., Smerin, Russell, and Ursano, 2014). Scientist Barbara McClintock discovered that without these structures, chromosomes would fuse, degrade, or recombine during mitosis and lead to chromosomal instability (Zhang et al., 2014). Over time, after each cellular division, the telomere shortens, unless counteracted by telomerase, the cellular enzyme responsible for adding telomeric DNA to the ends of the telomere (Epel et al. 2004).
In the absence of telomerase activity, as a result of the shortening, the cell will either enter senescence, or stop replicating; suffer apoptosis, or cell death; or continue to divide without protection, which can lead to potentially dangerous abnormalities (Biology of Aging, 2011). According to Harvard’s Masood Shammas (2011) “telomere length may therefore serve as a biological clock to determine the lifespan of a cell and an organism.”
In the human population, telomeres shorten at a rate of 24.8-27.7 base pairs per year, with studies showing that a “shorter than average telomere length for a specific age group, has been associated with increased incidence of age-related diseases and/or decreased life span” (Shammas, 2011). Along with age-related health conditions such as cardiovascular disease, diabetes, cancer and osteoporosis, elderly humans with shorter telomeres have a higher mortality rate that that of their peers with longer telomeres (Shammas, 2011). According to Shammas (2011), stress also increases the rate of telomere shortening. Glucocorticoid hormones released by the adrenal glands during periods of stress are known to reduce the amounts of antioxidant proteins and can increase oxidative damage to DNA, which can accelerate telomere shortening (Shammas, 2011).
While countless studies have shown a link between stress and poor health, a 2004 study conducted by Epel, Blackburn, Lin, Dhabhar, Adler, Morrow and Cawthon sought to find a direct link between stress and cellular aging. The study examined 58 healthy women, 19 of which served as the control group and were biological mothers of a healthy child; 39 were biological mothers of a chronically ill child, known as “caregivers” (Epel et al., 2004). Mean telomere length and telomerase activity were measured in the samples (Epel et al., 2004). The results of the study found that within the caregiver group, “the more years of caregiving, the shorter the mother’s telomeric length, the lower the telomerase activity, and the greater the oxidative stress, even after controlling for the mother’s age” (Epel et al., 2004). Citing the 2004 study by Epel et al., Shammas (2010) purported that “the difference in telomere length in [the] two groups of women was [the] equivalent to 10 years of life, indicating that the women under stress were at a risk for early onset of age-related health problems.”
A 2011 study by Entringer, Epel, Kumsta, Lin, Hellhammer, Blackburn, Wüst and Wadhwa further established that exposure to intrauterine stress was linked to shorter telomere length in adulthood. Noting that animal studies have reported intrauterine stressors as a contributing factor to shorter telomere length in a variety of tissues, Entringer et al. (2011) state that among preschool-age children, those who were born low birth weight had shorter leukocyte telomere length (LTL) than children of normal birth weight of the same age. In their study, Entringer et al. (2011) observed young adults whose mothers experienced high stress, or a negative life event, during pregnancy with young adults whose mothers did not experience any negative life events during pregnancy. The findings showed the LTL of adults in the stress group was 178 base pairs shorter, on average, than that of the control group (Entringer et al., 2011). This data suggests that the shortage of base pairs translates to the equivalent of 3.5 years of life expectancy relative to the control (Entringer et al., 2011).
Post-traumatic stress disorder (PTSD) is an anxiety disorder that can manifest following exposure to severe traumatic stress (Zhang et al., 2014). PTSD has been found to be associated with “dysregulation of bodily systems that have been linked with biological aging” due to sustained activation of the biological stress response (Zhang et al., 2014). Those suffering from the disorder were observed to have comparatively shorter LTL than that of control subjects (Zhang et al., 2014). A possible explanation for the shortening may lie in inflammation, a byproduct of increased sympathetic nervous system activation, which leads to increased cell turnover; the resulting oxidative stress then damages telomeric DNA and leaves the subject vulnerable to accelerated LTL shortening (Zhang et al., 2014).
Rapid telomere shortening has also been observed among individuals suffering from psychosocial stress and depression; the median telomere length for individuals suffering from long-term depression was 281 base pairs shorter than the control, accounting for 7 years of accelerated cellular aging (Zhang et al., 2014). This finding could also explain the increased morbidity for major depressive orders (MDD), in which “subjects had significantly shortened LTL compared to controls, with an estimated acceleration of biological cell aging of over 10 years” (Zhang et al. 2014).
While chronic stress has been shown to shorten telomere length and accelerate the aging process, a 2010 study by Puterman, Lin, Blackburn, O'Donovan, Adler and Epel maintained that not everyone under stress possessed definitively short telomeres; the findings suggest that the effects of stress can be minimized by physical activity. In contrast to the shortened telomeres of the chronically stressed, physical activity is linked with longer telomeres; the differences were observed in a national sample of identical twins as well as a comparison between athletes and a sedentary population (Puterman et al., 2010). The study found that “above around 40 minutes of vigorous physical activity over 3 days, stress is no longer associated with short telomeres” (Puterman et al., 2010).
The explanation for the benefit of exercise appears to lie with telomerase; physical activity increases telomerase activity, allowing for a slower degradation of the protective ends (Puterman et al., 2010). Puterman et al. (2010) also suggest that “exercise might also buffer telomere shortening through affecting the balance between oxidative stress and antioxidants.”
In conclusion, while science has not yet discovered a “fountain of youth,” or a way to stop the process of aging, scientists have identified significant contributing factors such as stress and exercise, which have the ability to respectively speed up or slow down the rate of aging among a population. The secret to a longer life may literally be a walk in the park. **
Works Cited
Biology of Aging. (2011, November). Retrieved from https://www.nia.nih.gov/health/publication/aging-under-microscope/what-aging
Entringer, S., Epel, E. S., Kumsta, R., Lin, J., Hellhammer, D. H., Blackburn, E. H., Wüst, S., & Wadhwa, P. D. (2011, June 03). Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proceedings of the National Academy of Sciences, 108(33). doi:10.1073/pnas.1107759108
Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2004, September 28). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences, 101(49), 17312-17315. doi:10.1073/pnas.0407162101
Puterman E., Lin J., Blackburn E., O'Donovan A., Adler N., & Epel E. (2010, May 26). The Power of Exercise: Buffering the Effect of Chronic Stress on Telomere Length. PLoS ONE 5(5): e10837. doi:10.1371/journal.pone.0010837
Shammas, M. A. (2011). Telomeres, lifestyle, cancer, and aging. Current Opinion in Clinical Nutrition and Metabolic Care, 14(1), 28–34. http://doi.org/10.1097/MCO.0b013e32834121b1
Zhang, L., Hu, X., Li, X., Li, H., Smerin, S., Russell, D., & Ursano, R. J. (2014). Telomere length – A cellular aging marker for depression and Post-traumatic Stress Disorder. Medical Hypotheses, 83182-185. doi:10.1016/j.mehy.2014.04.033
Entringer, S., Epel, E. S., Kumsta, R., Lin, J., Hellhammer, D. H., Blackburn, E. H., Wüst, S., & Wadhwa, P. D. (2011, June 03). Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proceedings of the National Academy of Sciences, 108(33). doi:10.1073/pnas.1107759108
Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2004, September 28). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences, 101(49), 17312-17315. doi:10.1073/pnas.0407162101
Puterman E., Lin J., Blackburn E., O'Donovan A., Adler N., & Epel E. (2010, May 26). The Power of Exercise: Buffering the Effect of Chronic Stress on Telomere Length. PLoS ONE 5(5): e10837. doi:10.1371/journal.pone.0010837
Shammas, M. A. (2011). Telomeres, lifestyle, cancer, and aging. Current Opinion in Clinical Nutrition and Metabolic Care, 14(1), 28–34. http://doi.org/10.1097/MCO.0b013e32834121b1
Zhang, L., Hu, X., Li, X., Li, H., Smerin, S., Russell, D., & Ursano, R. J. (2014). Telomere length – A cellular aging marker for depression and Post-traumatic Stress Disorder. Medical Hypotheses, 83182-185. doi:10.1016/j.mehy.2014.04.033
** Disclaimer: I HATE "in conclusion" paragraphs, but my instructor required it.