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The present study reviews the literature of psychoneuroimmunology (PNI) essential in relationship between exposure to stress, health, and the immune system of ageing. The complex physical, psychological, neurobiological, social, and behavioral factor of immunosencence refers to aging. The clinical aspect of the hypothalamus-pituitary-adrenal (HPA) axis decreased cell activity of the elderly and its important correlation. The study of psychoneuroimmunology addresses the complexity of the immune system as individual's age, if overlooked within the elderly population by assumption that all elderly individuals experience depression as they age. The clinical consequence of immunosencence leaves the elderly susceptible to various diseases, infections, and psychological stress (Bauer, 2005). The relevance of studying the ageing population, particularly in the developed countries, is the percentage of elderly 60 years and older represents the larger population (Ongrádi & Kövesdi, 2010). Statistical evidence as suggested by Ongrádi & Kövesdi (2010) in a recent study indicates the increase of elderly population in 1950 to 2000 and increase of 10 %, to a projected increase of 21 % by 2050.
Since people are living much longer, exposures to environmental and psychosocial factors increase the susceptibility of infections and diseases. Therefore, the relevance of exposure to life circumstance albeit lifestyle, unhealthy habits, and mental health problems influences immunity, and well-being. Literature implies the positive and negative consequences of the immune systems functions as people age. Significant data suggest a closer look at the theory of psychoneuroimmunology and stress, which derived decade ago with Hans Selye as a promising era of philosophy promoting potential change in the scientific world.
In 1956 Hans Selye, popularized the concept of stress. Defining stress as "the nonspecific response of the body to any demand upon it" Seyle 1974, (as cited in Goldstein & Koplin, 2007, p.110). Thus, any response to a contributory agent or stressor regardless of the nature affects the immune system (Goldstein & Koplin 2007). Considering stress as state of threatened homeostasis, Selye went on to introduce the popular and still widely recognized today as the General Adaptation Syndrome (GAS). The GAS theory consists of three stages.
The first stage is the alarm reaction, the flight, or fight response when the body is able to release adrenaline to combat stress, and maintaining homeostasis. Second stage, the resistant or adaptation this occurs if stress continues. During this stage blood pressure increase due to secretion of prolonged hormones, typically the body uses more energy and blood pressure increases. In essence, overuse of the body's natural defense mechanism can lead to fatigue, poor concentration, lethargy, irritability, illness, disease affecting the person mentally, physically, total well being. Third stage exhaustion this phase is when the body's energy and immunity decreases resulting in emotional and physical exhaustion. This stage refers to the depletion of body's energy and stress tolerance is low, progressively the person might collapse from exhaustion. Persons suffering from chronic depression or anxiety might incur these symptoms during the final stage of the GAS (Holistic Online 1998/2007).
Selye, (1974) argued that accumulated stress over time leaves chemical scaring showing signs of aging. The association brought forth by Hans Seyle suggesting that depression and other disorders and diseases in the elderly due to a dysfunctional immune system are significant in terms of immune response. In the past several decades, researchers theorized the association of stress response and its influence from a physiological and psychological perspective thus diminishing health in general if stress cannot be resolved impairing the immune system typically involving ageing.
The immune response within the ageing population, who experiences various levels of stress throughout a lifetime or immediacy of events, plays an important role in health behavior. Evidence suggests the interconnectedness between physiological, psychological, and immune function during stress impacts homeostasis (Thornton & Anderson, 2006). According to Thornton & Anderson, (2006) the affects of stress within the central nervous system influences the hypothalamic-pituitary-adrenal (HPA axis) and the sympathetic-adrenalmedullary, (SAM) hormones released during stressful events can affect immune function (Thornton & Anderson, 2006). Sufficient evidence in literature implies as people age, the immune system becomes less effective based upon various lifestyle choices, or circumstances, natural processing of immune functions and responses.
Merck (2010) suggests some of the following aspects of ageing response within the immune system, decreased capabilities of distinguishing between the self from non-self antibodies increasing autoimmune disorders. Macrophages which tend to destroy bacteria, cancer cells, and other antigens activation slow down with age. T-cell activation also responds less quickly to antigen as do the production of white blood cells in terms of responding to new antigens, in other words they lose responding memory (Merck, 2010). Physiologically suggesting decreases in antibodies attaching less to antigen as aging occurs indicating why depression, and diseases such as pneumonia, influenza, and other diseases such as cancer and infections occur in the older population due to less protein productivity (Merck, 2010). In other words, the immunological changes lend to a different aspect of immunosenescence from a psychological stress and hormonal stress pathology (Bauer, 2005). The susceptibility for adults over 65 years of age correlates to suppression of the immune system resulting from chronic stress over time (Robles, Glaser, & Kiecolt-Glaser, 2005). Considering one of the key components regulating response to infections and or injuries, is cytokines, which aid in reducing or increasing inflammation (Robles et al., 2005). The importance of understanding the mechanism of cytokines responses typically with the elderly population is their capabilities of responding to either anti-inflammatory or pro-inflammatory (Robles et al., 2005). According to Robles et al., (2005) pro-inflammatory involves various responses in order to regulate inflammation, brain activity, which affects of the endocrine system, behaviors and HPA axis by producing glucocorticoid hormones which properties consists of anti-inflammatory cytokines. Evidence shows the physiological changes within the immune system derived from the normal process of ageing and the efficacy of understanding the body's mechanism require psychological and psychosocial understanding.
The interaction between causation of disease, infection, along with psychosocial factors, stress, behaviors, and suggesting homeostasis is paramount to the ageing individual in terms of physical and emotional health. For that matter, the interaction between the immune system, endocrine, and nervous system and the body's reaction to stressing and or unhealthy habits does not suggest this occurs only in elderly phase of life. Behaviors, which elicit negative responses of immunity including psychosocial stressors, occur over a lifetime. Thus, the manner in which physiological and psychological perspectives indicates a collaborative entity (mind/body) in terms of ageing, health, and immune responses to invasive pathogens.
Pathogens and Ageing
Previous literature argues the implication of the immune system and susceptibility of disease is more frequent in aged populations. Accumulating evidence of the connection between the ageing processes of the immune system, immunosenescence, of older individuals and developing various diseases. For example, Pletz, Duda, Kappos, & Steck (2003) argues the causation of developing diseases is due to neural tissue-specific B and T cells, which tend to decreased central tolerance, and increased proinflammatory environment due to cytokine shifts and higher functional capacity of innate immune cells (Pletz, Duda, Kappos, & Steck, 2003).
Bauer, (2005) posits the involvement of the neuroendocrine aspect of immunosenescence considering cortisol/DHEA noted to have significant changes in the aged population. This research goes on to suggest the theory of ageing and association with psycho neuroendocrine process. Meaning psychological, behavioral, and stress factors of healthy ageing may influence and modulate changes in the immune system (Bauer, 2005). According to Maier & Watkins (2000), the brain and immune system function as one entity, therefore activation of immune cells cytokines, releasing information from blood and neural routes eliciting changes in neural activity (Maier & Watkins, 2000). Suggesting changes in cognition, mood, stress, and depression, in other words a shift in cytokines indicates not only a physiological response but also a psychological response typically noted in research to alter various functions of the immune system (Maier & Watkins, 2000). Ongrádi & Kövesdi (2010), who reported the severity and impact of diseases, argues the ageing immune system in relationship to bacteria, viruses, and disease as a challenge to the health care system and greatly influences ones quality of life. For example, the statistical rate of mortality increases with age for people over 65 in comparison to persons in their 20's - 40's specifically in the areas of pneumonia, influenza, and cancer. Ongrádi & Kövesdi (2010) goes on to argue the main factor of increases of infectious diseases in the elderly population is the "diminished or exhausted function of the immune system" (Ongrádi & Kövesdi, p.1, 2010). A physiological factor that influences ageing are immune responses to cellular mechanisms such as NK cells, macrophages, and neutrophil which is the largest fraction of white blood cells and the first line of defense against pathogens (Ongrádi & Kövesdi, 2010).
Innate Cell Activity and Immunosenescence
Literature indicates the role of cell dysfunction of the immune system of ageing persons. For example, Natural killer Cells (NK) play a significant role within the immune system as a defense against infections, diseases, and tumor growth (Gomez, Nomelini, Faunce, & Kovacs, 2008). NK cells cytotoxicity preservation appears in healthy ageing; however, in unhealthy ageing reports of decreased proliferation rates indicate a higher incident of infections and diseases (as cited by, Mariani et al., 2001) and decline in cytotoxicity ability of NK cells. Although studies indicate modest impairment in aged individuals in terms of capabilities of producing IFNy and proliferation in response to IL-2, suggesting further studies necessitate clarification of age-related NK function (Gomez et al., 2008). Other vital cell activity of the immune system is Macrophages, which, originates in the hematopoietic cells of bone marrow once they enter the blood, and monocyte continue to differentiate as macrophages migrating into tissue (Gomez et al., 2008). The function of macrophages involves phagocytosis of antigens microorganisms killing and invading tumors (as cited by Underhill and Ozinsky, 2002). Considering all the physiological functions of immune cell activity and immunosenescence Bauer, Jeckel, & Luz (2009) argues ample evidence shows a relationship between ageing chronic stress and immune system. Moreover, Bauer, Jeckel, & Luz (2009) reported healthy ageing associated with dehydroepiandrosterone (DHEA) and emotional distress increasing cortisol.
The impaired DHEA secretion collectively with the increase of cortisol results in an enhanced exposure of lymphoid cells to harmful glucocorticoid actions (Bauer, Jeckel, & Luz, 2009). Recognizing that ageing is a slow and eminent process, the involvement of the innate cell activity influences several cellular activities with in the body's response to stress, psychosocial events, physical and mental well-being. It is important to understand another factor aside from immunosenescence is the changes within the endocrine system. Decreases in hormone levels such as growth hormone (GH), sex hormones, and dehydroepiandrosterone (DHEA) contributing factors of ageing (Bauer, Jeckel, & Luz, 2009). Previously stated there evidence suggesting that ageing is associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis increasing production of cortisol (Robles et al., 2005). Cortisol and dehydroepiandrosterone (DHEA) function as noted by de Bruin, Vieira, Rocha, & Viana, (2002) suggests a relationship to ageing and cognitive function, which regulates mood and behavior activities sometimes due to prolonged stress from a clinical perspective dysregulation of the immune system. Considering disruption of homeostasis within the elderly population influenced not only from a physiological viewpoint, yet from a psychological viewpoint.
Psychological Implications of Ageing, Stress, and Immunity
More and more scientific evidence suggesting a correlation between physiological and psychological factors in terms of immunosenescence although literature suggests controversy exists. Bauer, Jackel, & Luz (2009) argues psychological distress might be an important aspect of immunosenescence since numerous psychological and behavioral changes in cognition, sleep disturbances and major depression are associated with ageing (Bauer et al., 2009). In previous research (Bauer et al., 2009) observed frail and health elderly finding an association of increased levels of pro-inflammatory cytokines indicating possible further immunological diseases. Observing healthy elderly (Bauer et al., 2009) found a significant association with psychological distress; healthy elderly appeared more stressed, and anxious. The data collection of this research indicated HPA axis showed significant activation, along with increased cortisol, levels as noted in major depression or during chronic stress (Bauer et al., 2009).
Stress described as changes in the environment albeit external or internal disrupting homeostasis originally introduced by Walter Cannon in 1929 (as cited in Leonard & Myint, 2009). The coexistence between the immune, endocrine, and neurotransmitters and influence on behaviors is the premise of psychoneuroimmunology, actually an old theory currently seeking attention.