Immunodeficiency of the Elderly

Saltzman, Robin; Peterson, Phillip K.

doi:10.1093/clinids/9.6.1127

Cited by 186 publications

(84 citation statements)

References 105 publications

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“…Aging is associated with progressive decline in immune functions, [35][36][37][38] which is assigned in part to increased apoptosis. [27][28][29][39][40][41][42][43][44][45][46][47] During aging there is an increased production of proinflammatory cytokines, including TNF-a.…”

Section: Discussionmentioning

confidence: 99%

Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans

Gupta

Kim

et al. 2005

Cell Death Differ

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In human aging, lymphocytes display increased sensitivity to tumor necrosis factor-a (TNF-a)-induced apoptosis. TNF-a induces both survival and apoptotic signals. The survival signal is mediated by the activation of NF-jB. Although a role of certain proapoptotic molecules in aging has been reported, a role of altered NF-jB signaling pathway has not been explored in detail. In this study, we have compared TNF-ainduced activation of NF-jB, phosphorylation of IjBa, and the expression of IKKb between lymphocytes from young and aged humans. Furthermore, we have explored a role of IKKb in increased susceptibility of lymphocytes from aged humans to TNF-a-induced apoptosis. Lymphocytes from aged humans displayed decreased activation of NF-jB, reduced phosphorylation of IjBa, and decreased expression of IKKb. In addition, overexpression of IKKb in lymphocytes from aged humans normalized TNF-a-induced apoptosis to the level of young subjects. These data suggest a deficiency of NF-jB signaling pathway and a role of IKKb, at least in part, for increased sensitivity of lymphocytes from aged humans to TNF-a-induced apoptosis.

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Section: Discussionmentioning

confidence: 99%

Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans

Gupta

Kim

et al. 2005

Cell Death Differ

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“…Elderly patients are susceptible to septic shock and their prognoses are thereby apparently worse than that of young patients [1][2][3][4][5]. The mechanisms of such vulnerability to infections in the elderly have been ascribed to a breakdown in the anatomic barriers, underlying illnesses, or the declining capacity of the immune system [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…These cells may be closely involved in the agerelated host immune response by their high potential to produce IFN-c [24,25]. LPS-induced lethal shock, the most severe type of endotoxemia, frequently occurs in the elderly [1][2][3][4][5]. We previously demonstrated that NK1 + T cells and their IFN-c production might be involved in the mouse generalized Shwartzman reaction induced by IL-12 and subsequent LPS challenge [21].…”

Section: Introductionmentioning

confidence: 99%

Critical role of the liver CD8⁺ CD122⁺ T cells in the generalized Shwartzman reaction of mice

et al. 2005

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We examined the role of mouse CD8+ CD122+ T cells, which increase in number with age, in the generalized Shwartzman reaction. This reaction was induced by IL‐12 priming and subsequent LPS challenge (after 24 h) in mice of various ages (4–50 weeks of age). Although most young mice (4 or 6 weeks of age) survived, mortality essentially increased with increasing age of the mice, and all mice of 20 weeks of age or older died within 48 h. Serum TNF‐α levels after LPS challenge also increased age dependently. The neutralization of either IL‐12‐induced IFN‐γ or LPS‐induced TNF‐α improved the survival of middle‐aged (25‐week‐old) mice. Both IFN‐γ production after IL‐12 priming and TNF‐α production from the liver mononuclear cells after LPS challenge were also prominent in the middle‐aged mice. CD8+CD122+ T cells cultured with IL‐12 produced a much larger amount of IFN‐γ than CD8+CD122– T cells. Although the depletion of NK/NK T cells did not decrease the IFN‐γ or TNF‐α production in the Shwartzman reaction of the middle‐aged mice, an additional depletion of CD8+CD122+ T cells did decrease such production and also improved mouse survival. Furthermore, young mice transferred with CD8+CD122+ T cells from aged B6 nude mice showed an enhanced Shwartzman reaction.

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“…Some researchers have suggested that a decrease in immune function predictably accompanies the aging process (63), and many preclinical and observational studies have demonstrated that micronutrient supplementation can enhance immune function, which is strongly related to cancer risk and the process of cancer development (64,65). Therefore, elderly people could improve their immune function by supplementing multiple micronutrients, and mortality and morbidity could be reduced.…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis: Low-Dose Intake of Vitamin E Combined with Other Vitamins or Minerals May Decrease All-Cause Mortality

Jiang

Pan

et al. 2014

J Nutr Sci Vitaminol

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The aging of the population is one of most common phenomena in many countries, especially developed countries. With advancing age, people are more likely to develop CVD (cardiovascular disease) and cancer, the two leading causes of death. Free oxygen radicals increase levels of lipid peroxidation and damage DNA and other subcellular structures, contributing to the development of CVD and cancer (1-3). Therefore, extensive preclinical and observational studies have been conducted to evaluate the preventive effects of antioxidant vitamins and minerals against oxidative stress and oxidative injury-related chronic diseases (4-6).Vitamin E is well-known as the most important lipid soluble antioxidant (7). In animal models, a-tocopherol, the active form of antioxidant vitamin E, has been associated with reductions in atherosclerotic lesions, smooth muscle cell proliferation and platelet adherence and aggregation (8-10). On the other hand, it has been widely demonstrated that vitamin E and certain other agents such as vitamin C (ascorbic acid), b-carotene and selenium cooperatively reduce oxidative stress (5, 6, 11, 12). The antioxidant effects of vitamin E can be strengthened by vitamin C (5), b-carotene and selenium (11, 13), and vitamin E can play a biochemical role that is analogous to the role of zinc in stabilizing membrane structure and reducing peroxidative damage (14). Vitamin E acts as the primary antioxidant and the resulting vitamin E radical then reacts with vitamin C to regenerate vitamin E (15).However, meta-analyses evaluating the antioxidant effect of vitamin E have reported a disappointing effect on survival (16)(17)(18)(19)(20). Among these meta-studies, the most recent and systematic study was reported 9 y ago and demonstrated that low-dose vitamin E slightly but non-significantly decreased the mortality but high-dose vitamin E increased mortality (18). High dosage of vitamin E intake has been revealed to contribute to many clinical disorders (21), which is consistent with the increased mortality for high-dose vitamin E. Otherwise, another meta-study on vitamin E, which used the same inclusion criteria as Miller et al. (18) but adopted a different meta-analytic method, also got a disappointing result (22, 23). Such an effect could obscure the effect of vitamin E in studies without considering the dosage, which is seen in several reports (16, 17, 19, 20 Neither vitamin E intake alone nor combined with other agents is associated with a reduction in all-cause mortality. But a low dose (,400 IU/d) of vitamin E combined with other agents is correlated with a reduction in all-cause mortality, and vitamin E intake combined with other agents is correlated with a reduction in the mortality rate among individuals without probable or confirmed diseases.

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Immunodeficiency of the Elderly

Cited by 186 publications

References 105 publications

Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans

Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans

Critical role of the liver CD8⁺ CD122⁺ T cells in the generalized Shwartzman reaction of mice

Meta-Analysis: Low-Dose Intake of Vitamin E Combined with Other Vitamins or Minerals May Decrease All-Cause Mortality

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Immunodeficiency of the Elderly

Cited by 186 publications

References 105 publications

Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans

Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans

Critical role of the liver CD8+ CD122+ T cells in the generalized Shwartzman reaction of mice

Meta-Analysis: Low-Dose Intake of Vitamin E Combined with Other Vitamins or Minerals May Decrease All-Cause Mortality

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Critical role of the liver CD8⁺ CD122⁺ T cells in the generalized Shwartzman reaction of mice