Impact of Stress on Immunosenescence

The immune system defends the body against several internal (such as defective cells) and external (such as bacteria and viruses) threats by eliminating pathogens. It consists of two linked mechanisms called innate and adaptive immunity. Natural killer (NK) cells, phagocytes, and complements are just a few examples of the cells and different proteins in the innate branch of the immune system, which act as the body’s first line of defense against infection. These cells and proteins are the first to mount a defense against infections due to their nonspecificity. They also stimulate the immune system’s adaptive branch through cytokine interaction. The adaptive system takes more time to react to threats because it generates antigen-specific immunity [1].

Figure 1: Body’s protection by the immune system [1].

This system reacts to the initial antigen exposure by forming lymphocytes with a high level of specificity and “memory” for the challenge, enabling a subset of lymphocytes to react more quickly if the pathogen resurfaces. Antigen-presenting cells and lymphocytes are the two main cell types that make up the adaptive branch. T lymphocytes, which are in charge of destroying infected cells in response to an antigen, and B lymphocytes, which are responsible for producing large quantities of antibodies in response to an antigen, are the two main lymphocyte populations. Increases in one branch can reduce the effectiveness of the other because the innate and adaptive branches cooperate [1,2].

What Is Immunosenescence?

Immune function decreases naturally as people age [3,4]. This process of aging is known as immunosenescence [2]. Disease and further senescence are caused by immunosenescence [5]. Immunosenescence plays a significant role in age-related health issues like cancer and cardiovascular disease, as well as a diminished ability of the aged to respond to immunizations [5]. However, not all immune systems deteriorate with time [2,6,7]. Stress also causes a decrease in immunological function [3,4,7]. Worse, researchers indicate that the impacts of stress and aging interact. Age-related immunological deterioration is frequently more pronounced in older adults than in younger adults, and psychological stress can both imitate and exacerbate the effects of aging. Additionally, traumatic events that occur very early in life might change how the immune and neurological systems respond. We discuss the different effects of stress on immune function by means of research [4].

Figure 2: Immunosenescence Process [2].

Stress is a condition that is compatible with psychic tension led by a variety of internal and external stimuli, resulting in a homeostatic imbalance in body functions and neurological dysfunction in the nervous system [6,8]. Social and psychological stressors are an indivisible part of daily life and can have a profound impact on one’s life [4,8].

Figure 3: The Stress Response Cycle [3].

During their lifespan, people are exposed to a variety of stressors, with effects that develop at various rates due to differences in stress exposure, stress-buffering, stress reaction, stress duration (recovery), and restorative mechanisms [3,6].

“Allostasis” refers to the body’s capacity to adapt and sustain homeostasis in the face of stimuli. The body is protected against internal and external stress during allostasis via the autonomic nervous system, hypothalamus-pituitary-adrenal axis, cardiovascular, metabolic, and immune systems. Under the influence of the stressor, the following alterations were seen in the biological syndrome of stress known as the “General Adaptation Syndrome”: stomach bleeding ulcers, enlargement of the adrenal cortex, atrophy in the thymus and other lymphoid tissues and duodenum [6].

The three phases of this syndrome were later found:

  • Alarm Phase: The body’s defense mechanisms are mobilized, and the central nervous system (CNS) is activated. The sympathetic nervous system and the pituitary gland are stimulated by the stressor [6].
  • Resistance or Adaptation Phase: Cortisol, norepinephrine (NE), and epinephrine (E) are secreted in high amounts during this phase [6].
  • Exhaustion Phase: If the adaptation fails and the stress persists, the immune system is suppressed, the compensatory mechanisms are damaged, and heart, kidney, and other diseases may begin to appear [6] .
Figure 4: The Three Phases of Selye’s General Adaption Syndrome [4].

The Impact Of Stress On Immunosenescence

Psychological stressors cause the immune system to undergo several changes, and the severity of these changes varies depending on how long the stressor has been present. Short-term stressors cause minor changes in the immune system, whereas longer-term stressors (chronic) cause more significant changes. The immune system prepares itself for potential pathogen exposure in response to an acute challenge, which results in an elevation of some innate immunity components and a decrease in lymphocyte proliferation. The organism is protected from impending danger by these brief modifications in the regulation, which downregulate an hour after the threat has passed [1,4,9].

However, more significant alterations in immunological indicators occur with increasing stressor duration, including decreased B-lymphocyte concentrations, weakened vaccination responses, slower wound healing, and decreased NK cell activity [1,3,4,6].

The stress response’s adaptability starts to decrease as stressors become more persistent (chronic). Beginning with a decrease in adaptive immunity, an increase in inflammatory markers including proinflammatory cytokines and CRP, and a decrease in various facets of innate immunity, changes start to emerge that are comparable to those seen with age [1,4].

Figure 5: Effect of Stressor on Immune Functioning [5].

But Is Stress That Effective On The Immune System?

Data from the Health and Retirement Study, a sizable, nationally representative sample of U.S. persons over 50, was observed to understand better why people of the same chronological age can have varied immunological ages. Participants in the HRS are questioned by researchers about a variety of stressors, such as stressful life events, major lifetime trauma, and chronic stress [5].

Also, HRS researchers have begun collecting blood from a sample of participants and counting the quantity of several immune cell types, including white blood cells. These cells are crucial to the immune system’s defenses against bacteria, viruses, and other foreign invaders. This is the first time a comprehensive nationwide survey has gathered such in-depth data on immune cells [5].

The ability of T cells in the immune system to fight infections declines with age. By examining the information from 5,744 HRS participants who gave blood and responded to stress survey questions, it was discovered that those who reported feeling more stress had a lower percentage of “naive” T cells, which are young cells required to battle foreign invaders and the immune system hasn’t come across before. Additionally, they have a higher percentage of “late differentiated” T cells, which are older cells that are no longer able to fight intruders and instead create proteins that can increase inflammation. A person’s immune system is more advanced if they have a low percentage of more recent T cells and a high percentage of older T cells [4,5].

The relationship between stress and accelerated immunosenescence, however, wasn’t as strong after taking into account a bad diet and insufficient exercise. This implies that enhancing these healthy habits can reduce the risks related to stress [3,5].

The relationship between stress and immune cell ageing was also reduced if we considered the possibility of exposure to cytomegalovirus, a common and mostly asymptomatic virus that has been shown to accelerate immunosenescence. Researchers have identified that stress can induce CMV to flare up even though the virus generally remains dormant in the body. This forces the immune system to devote more resources to fighting the reactivated virus [5].

Sustained infection control can deplete naive T cell reserves and produce more worn-out T cells, which circulate throughout the body and lead to chronic inflammation, a major risk factor for age-related disease. The connection between stress and accelerated immunosenescence is clarified by this study [5].

Immunosenescence differs from individual to individual. Stress and ageing are two factors contributing to this difference. Understanding how stress contributes to immunosenescence can help explain why various diseases and vaccinations elicit diverse immune system reactions [5]. Immune systems that are younger are better able to overcome diseases and produce protective immunity from vaccines. As a result, the solutions that might be created can both serve to improve people’s quality of life and lessen the load on hospitals [1].

More research is required to determine whether stress reduction or lifestyle changes (diet and exercise) can help immunosenescence as well as to comprehend the interactions between stress and latent pathogens like the cytomegalovirus that result in disease and death. In order to lessen the immunosenescence effects of stress, the researchers suggested that universal CMV vaccination could be a reasonably easy and potentially effective treatment [5].

References:

  1. Jennifer R. Piazza, David M. Almeida, Natalia O. Dmitrieva, Laura C. Klein, Frontiers in the Use of Biomarkers of Health in Research on Stress and Aging, The Journals of Gerontology: Series B, Volume 65B, Issue 5, September 2010, Pages 513–525, https://doi.org/10.1093/geronb/gbq049
  2. Mois ́es E. Bauer,aCristina M. Moriguchi Jeckel,band Clarice Luzc. (2009, February 9). The role of stress factors during aging of the immune system. Retrieved July 2, 2022, from https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2008.03966.x
  3. Louise C. Hawkley, John T. Cacioppo,Stress and the aging immune system,Brain, Behavior, and Immunity,Volume 18, Issue 2,2004,Pages 114-119,ISSN 0889-1591, https://doi.org/10.1016/j.bbi.2003.09.005. (https://www.sciencedirect.com/science/article/pii/S0889159103001466)
  4. Graham, J. E., Christian, L. M., & Kiecolt-Glaser, J. K. (2006). Stress, age, and immune function: toward a lifespan approach. Journal of behavioral medicine29(4), 389–400. https://doi.org/10.1007/s10865-006-9057-4
  5. Leane Perim Rodrigues, Vitória Rodrigues Teixeira, Thuany Alencar-Silva, Bianca Simonassi-Paiva, Rinaldo Wellerson Pereira, Robert Pogue, Juliana Lott Carvalho,Hallmarks of aging and immunosenescence: Connecting the dots, Cytokine & Growth Factor Reviews,Volume 59,2021,Pages 9-21,ISSN 1359-6101, https://doi.org/10.1016/j.cytogfr.2021.01.006. (https://www.sciencedirect.com/science/article/pii/S135961012100006X)
  6. Kocatürk, P. A. (2000). STRESE CEVAP. Ankara Üniversitesi Tıp Fakültesi Mecmuası , 53 (1) , . DOI: 10.1501/Tipfak_0000000421
  7. Eric Klopack Postdoctoral Researcher in Gerontology. (2022, June 15). Social stress can speed up immune system aging – new research. The Conversation. Retrieved July 2, 2022, from https://theconversation.com/social-stress-can-speed-up-immune-system-aging-new-research-184905
  8. Selye, H. (1956). What is stress. Metabolism5(5), 525-530.
  9. Bauer, M. E. (2005). Stress, glucocorticoids, and ageing of the immune system. Stress8(1), 69-83.

Visual References:

  1. https://www.everydayhealth.com/healthy-living/all-about-immunity-and-the-immune-system/
  2. Leane Perim Rodrigues, Vitória Rodrigues Teixeira, Thuany Alencar-Silva, Bianca Simonassi-Paiva, Rinaldo Wellerson Pereira, Robert Pogue, Juliana Lott Carvalho,Hallmarks of aging and immunosenescence: Connecting the dots, Cytokine & Growth Factor Reviews,Volume 59,2021,Pages 9-21,ISSN 1359-6101, https://doi.org/10.1016/j.cytogfr.2021.01.006. (https://www.sciencedirect.com/science/article/pii/S135961012100006X)
  3. https://psychcentral.com/stress/the-stress-response-cycle#How-to-complete-the-stress-cycle
  4. Stress, Lifestyle, and Health – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/The-three-stages-of-Selyes-general-adaptation-syndrome-are-shown-in-this-graph_fig18_291348598
  5. https://www.simplypsychology.org/stress-immune.html

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