The impact of ageing on monocytes and macrophages

Maeyer, Roel P.H. De; Chambers, Emma S.

doi:10.1016/j.imlet.2020.12.003

Cited by 179 publications

(127 citation statements)

References 151 publications

(177 reference statements)

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“…It is also worth to mention that these basal changes explain why under specific stimulation such as by E. coli the stimulability of ROS production was less in all subject groups compared to HC, further decreasing the defense of the organism when specifically needed. This mirrors what is seen in aging and other age-related diseases [ 48 , 98 , 124 , 125 ]. The role of free radicals can thus be considered double; both to eliminate aggressors but also to pave the way by intracellular signalling to pro-inflammatory mediators promoting chronic neuroinflammation [ 141 ].…”

Section: Discussionsupporting

confidence: 67%

“…We found that the proportions of non-classical monocytes increased through the spectrum of AD from SMC to AD, while the intermediate monocyte subset increased only in MCI and AD patients at the expense of classical monocytes. The intermediate and non-classical monocytes seem to be more inflammatory [ 115 – 117 ] as has been shown also in other inflammatory diseases (e.g., heart failure [ 109 , 118 , 119 ]), as well as in aging per se [ 120 – 124 ], however this was not the case in studies where no change at the basal level was found [ 125 ]. This increased propensity to higher inflammatory phenotype has been attributed to the expression of CD16 by both intermediate and non-classical monocytes, which were suggested to resemble the senescent monocyte population with increased inflammatory potential due to their SASP state [ 122 – 124 ].…”

Section: Discussionmentioning

confidence: 97%

“…The intermediate and non-classical monocytes seem to be more inflammatory [ 115 – 117 ] as has been shown also in other inflammatory diseases (e.g., heart failure [ 109 , 118 , 119 ]), as well as in aging per se [ 120 – 124 ], however this was not the case in studies where no change at the basal level was found [ 125 ]. This increased propensity to higher inflammatory phenotype has been attributed to the expression of CD16 by both intermediate and non-classical monocytes, which were suggested to resemble the senescent monocyte population with increased inflammatory potential due to their SASP state [ 122 – 124 ]. The increase of these more inflammation-prone monocytes has been shown in reaction to Aβ in AD patients compared to MCI or healthy subjects [ 126 ], but this is the first time that this shift from less-inflammatory monocytes towards more proinflammatory cells among the resting, isolated human blood monocytes has been shown to occur through the spectrum of consecutive clinical stages of AD.…”

Section: Discussionmentioning

confidence: 97%

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Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Munawara

Catanzaro

et al. 2021

Immun Ageing

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Background Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. Objectives AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. Results We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. Conclusion Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

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Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Munawara

Catanzaro

et al. 2021

Immun Ageing

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“…Considered a primary hallmark of aging, telomere attrition causes the loss of chromosome protective structures as they gradually get shorter [2]. This shortening process has also been closely connected with inflammation [41,42].…”

Section: Telomere Attritionmentioning

confidence: 99%

Hallmarks of Aging in Macrophages: Consequences to Skin Inflammaging

Guimarães

Almeida

Santos

et al. 2021

Cells

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The skin is our largest organ and the outermost protective barrier. Its aging reflects both intrinsic and extrinsic processes resulting from the constant insults it is exposed to. Aging in the skin is accompanied by specific epigenetic modifications, accumulation of senescent cells, reduced cellular proliferation/tissue renewal, altered extracellular matrix, and a proinflammatory environment favoring undesirable conditions, including disease onset. Macrophages (Mφ) are the most abundant immune cell type in the skin and comprise a group of heterogeneous and plastic cells that are key for skin homeostasis and host defense. However, they have also been implicated in orchestrating chronic inflammation during aging. Since Mφ are related to innate and adaptive immunity, it is possible that age-modified skin Mφ promote adaptive immunity exacerbation and exhaustion, favoring the emergence of proinflammatory pathologies, such as skin cancer. In this review, we will highlight recent findings pertaining to the effects of aging hallmarks over Mφ, supporting the recognition of such cell types as a driving force in skin inflammaging and age-related diseases. We will also present recent research targeting Mφ as potential therapeutic interventions in inflammatory skin disorders and cancer.

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“…The immunosenescence is characterized by a progressive decrease in the effectiveness of the immune system associated with aging, increasing the susceptibility to infections in older adults due to the impaired innate and adaptive immune response [10]. For example, during aging occurs a dysfunctional antigen-presenting cell, reduced chemotaxis to inflammatory stimuli of natural killers, neutrophils [11,12], reduced activity in bacterial phagocytosis by monocytes and macrophages [12,13]. There is also a reduced antibody response to exogenous antigens and vaccines by B-cells [14].…”

Section: Introductionmentioning

confidence: 99%

A ligated intestinal loop mouse model protocol to study the interactions of Clostridioides difficile spores with the intestinal mucosa during aging

Castro-Córdova

Paredes-Sabja

2021

Preprint

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The interaction of the Clostridioides difficile spores with the intestinal mucosa contribute to the persistence and recurrence of the infection. Advanced age is one of the main risk factors to manifest C. difficile infection and recurrence. However, the interaction of C. difficile spores with the intestinal mucosa during aging has not been evaluated. In the present work, we provide a detailed protocol with all the critical information to perform an intestinal ligated loop. Using this technique in a mouse model, we evaluated C. difficile spore adherence and internalization to the ileum and colonic mucosa during aging. Consequently, our data suggest that spore internalization in the ileum and colonic mucosa is higher in elderly than in adults or young mice. Also, our data suggest that spore-adherence to the ileum and colonic mucosa decreases with aging.

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The impact of ageing on monocytes and macrophages

Cited by 179 publications

References 151 publications

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Hallmarks of Aging in Macrophages: Consequences to Skin Inflammaging

A ligated intestinal loop mouse model protocol to study the interactions of Clostridioides difficile spores with the intestinal mucosa during aging

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