The aging innate immune system

Gómez, Christian R.; Boehmer, Eric D.; Kovacs, Elizabeth J.

doi:10.1016/j.coi.2005.07.013

Cited by 275 publications

(171 citation statements)

References 29 publications

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“…In humans, ageing is associated with significant changes in the innate immune system including impairment of neutrophil and macrophage phagocytic activity, increased production of pro-inflammatory cytokines and reduced antibacterial defence [23].…”

Section: Discussionmentioning

confidence: 99%

Age-related loss of CpG methylation in the tumour necrosis factor promoter

et al. 2011

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Background: Dysregulated production of TNF has been implicated in the pathogenesis and severity of inflammatory rheumatic diseases, many of which show age-related increased incidence. Ageing is also associated with changes in the immune system including higher systemic levels of pro-inflammatory cytokines.Methylation of DNA is an important regulator of gene expression and changes with age.Objective: In this study we investigated whether the DNA methylation status of the TNF promoter changed with age in peripheral blood leukocytes and macrophages. Methods and results:Using pyrosequencing assays we detected age-related demethylation of CpG motifs (-304, -245 and -239) Conclusions: These data suggest a potential role of accrued changes in DNA methylation in the development of age-related inflammatory diseases, such as rheumatoid arthritis and polymyalgia rheumatica, in which TNF is a pivotal mediator.3

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Section: Discussionmentioning

confidence: 99%

Age-related loss of CpG methylation in the tumour necrosis factor promoter

et al. 2011

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“…Thus, both peripheral homeostasis and DP differences would be denoting a different interindividual maintenance of the naive T-cell pool. Another well-known age-related immune change is in the systemic inflammation status of the elderly (Gomez et al 2005;De Martinis et al 2006). Once we assessed the thymic functionality and its impact on peripheral T-cell pools, we decided to analyze the inflammation status of our cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the innate immune system, many altered functions and inflammation markers (Gomez et al 2005;De Martinis et al 2006) predicting frailty in the elderly have been reported. The failure in defenses against bacteria might indicate that the function of neutrophils is seriously impaired in the elderly (Lord et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Thymopoiesis in elderly human is associated with systemic inflammatory status

Ferrando‐Martínez

Franco

Hernández

et al. 2009

AGE

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Immunosenescence studies of age-related immune system damage focused on clinical lymphopenic situations or androgenic blockade have revealed new insights about adult human immune reconstitution. However, as far as we know, the extent of lymphopoiesis in the thymus of elderly humans remains unclear. To this effect, we have analyzed 65 adult human thymuses (from 36 to 81 years; median age 68.6 years) obtained from patients who underwent cardiac surgery. Our results show a correlation between CD4 + CD8 + double-positive (DP) cells and both the age (inverse) and percentage (direct) of peripheral naive T cells, indicating that the thymus is still able to affect the peripheral lymphocyte pool even in the elderly. We also found significant correlation between the degree of thymopoiesis and the inflammation markers, as shown by the inverse correlations between DP and the percentage of neutrophils and IL-6 levels and the percentage of peripheral lymphocytes. Furthermore, in a multivariate linear regression the percentage of DP and IL-7 levels, but not age, were independently associated with the percentage of neutrophils. In conclusion, the thymus maintains, even in the elderly, an active thymopoiesis that rejuvenates the peripheral naive T-cell pool. Moreover, age-related thymopoietic decay is associated with the peripheral inflammation markers.

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“…Moreover, both the function and integrity of epithelial barriers decrease with age (21). Such conditions are likely to lead to a highly proinflammatory environment in elderly donors and recipients, probably involving IL-17, which may play a role in the initiation of innate immune responses and ischemia reperfusion injury (22).…”

Section: Discussionmentioning

confidence: 99%