Infectious and Inflammatory Disease Risk in the Elderly
In a review published in Immunology and Allergy Clinics of North America Kathi Heffner from the Department of Psychiatry, University of Rochester Medical Center, Rochester, New York outlines recent data suggesting that immunosenescence, endocrinosenescence and age-related dysregulation of stress response systems are closely intertwined.
Aging is accompanied by immunosenescence. Immunosenescence refers to the dysfunction and gradual deterioration of the immune system associated with aging. This overall change in immunity contributes to the increased susceptibility of the elderly to infectious disease, cancer and pathological conditions relating to inflammation (e.g. cardiovascular disease and possibly Alzheimer’s disease) and to the poor outcome of vaccination. Immunosenescence is also implicated in chronic, low level inflammation that is linked to a host of chronic, age-related diseases, including rheumatoid arthritis, atherosclerosis, osteoporosis, and type-2 diabetes.
Psychological stress has similar costs: chronic stress, such as ongoing interpersonal strain or caregiving for a spouse with dementia, has many of the same dysregulating effects on inflammatory processes as seen with aging.
The natural age advancement is also accompanied by the aging and remodeling of the endocrine system – endocrinosenescence, and this process is closely related to immunosenescence, due to the immunomodulating properties of endocrine hormones. To add further complexity, aging and endocrinosenescence also affect the activity of the stress system in terms of stress hormones output, responsiveness and sensitivity of target tissues.
For older adults, physiological activation in response to stressors is transposed upon age-related dysregulation of stress response systems. Importantly, neuroendocrine function, like immune function, is altered with both aging and chronic stress. Accordingly, aging and stress-related neuroendocrine dysregulation may combine to further disrupt immune function, increasing risk for or exacerbating inflammatory disease in older adults.
In the Immunology and Allergy Clinics of North America review Dr. Heffner also highlights evidence indicating potentially additive or synergistic effects of immunosenescence and stress on immune and inflammatory dysregulation in older adults, further increasing disease risk.
The author of this review discusses that immunosenescence is characterized by two, inter-related changes in immunity. The first is related to chronic activation of the innate and inflammatory responses, characterized by increasing levels and impaired synthesis of pro-inflammatory cytokines and particularly interleukin-6 (IL-6). Indeed, IL-6 is a potent predictor of mortality in older adults, and IL-6 and other pro-inflammatory mediators have been implicated in the development of a host of inflammatory diseases, including cardiovascular disease, type 2 diabetes, osteoporosis, and arthritis.
The second is associated with an impaired T helper (Th)1/Th2 balance, and most likely a shift towards Th2 responses, marked by increases in IL-10 secretion and expression. This shift is linked to increased risk for or exacerbation of atopic allergy, allergic rhinitis, asthma, autoimmunity and chronic infection in susceptible individuals. Notably, chronic stress, like age, is associated with increases in circulating levels of pro-inflammatory cytokines, as well as a shift toward Th2 responses.
Dr. Heffner argues that age-related changes of sympathetic nervous systems activity and cortisol, DHEA, and adreno-medullary hormones’ output may be causally linked to changes of pro- and anti-inflammatory cytokine production, and regulation of Th1 and Th2 responses.
The sympathetic nervous system (SNS) shows changes with age, with increased overall tonic activity at rest, primarily indexed by norepinephrine (NE) output at neuroeffector junctions. Higher basal circulating levels of NE have also been observed in older compared to younger men. In contrast, epinephrine (EP) output by the adrenal medulla under resting conditions was shown to decline with age. However, age-related reductions in EP clearance from circulation can obscure interpretations about EP output by the adrenal medulla when measuring circulating catecholamine levels.
In addition, NE spillover from neuroeffector junctions into circulation increases with age; thus it is unclear whether circulating levels of NE are more a function of spillover or age-related changes in NE output by the adrenal medulla. In sum, relatively little is known about the effects of age on sympathoadrenal activity during stress, but evidence suggests there may be age-related differences in adrenal output and clearance of catecholamines. The health implications of these age-related changes remain to be determined.
All the above-mentioned changes may contribute to the increased susceptibility of the elderly to infectious disease and pathological conditions relating to inflammation during immunosenescence.
The author concludes that developmental changes in the interplay of stress hormones and immunity should be considered to fully understand the implications of neuroendocrine stress responses for infectious/inflammatory disease risk in the elderly.
SOURCE: Immunol Allergy Clin North Am 2011, 31:95.
