As we age: Does slippage of quality control in the immune system lead to collateral damage?

Müller, Ludmila; Pawelec, Graham

doi:10.1016/j.arr.2015.01.005

Cited by 47 publications

(21 citation statements)

References 93 publications

(105 reference statements)

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“…These interactions are present at the various levels of organization -at the local, as well as at the whole organism level -by sharing a common language of a wide range of cytokines, receptor molecules, hormones, neuropeptides, metabolic and neurotrophic factors allowing crosscommunication (38,39). Particularly in the process of aging, this reciprocal cross-talk may under certain circumstances permit augmentation of maladaptive inflammatory loops, which could disturb homeostasis and contribute to the age-related functional alterations or even to pathological conditions (2,40,41). Several analytical techniques to investigate these interactions have been established so far, but our understanding of the interplay between different factors in such interrelated processes is still in its infancy.…”

Section: Discussionmentioning

confidence: 99%

Network Topology Dynamics of Circulating Biomarkers and Cognitive Performance in Older Cytomegalovirus-seropositive or -seronegative Men and Women

Benedetto

Müller

Rauskolb

et al. 2019

Preprint

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Background: Cytokines are signaling molecules operating within complex cascade patterns and having exceptional modulatory functions. They impact various physiological processes such as neuroendocrine and metabolic interactions, neurotrophins' metabolism, neuroplasticity, and may affect behavior and cognition. In our previous study, we found that sex and Cytomegalovirus (CMV)-serostatus may modulate levels of circulating pro-and antiinflammatory cytokines, metabolic factors, immune cells, and cognitive performance, as well as associations between them. Results: In the present study, we used a graph-theoretical approach to investigate the network topology dynamics of 22 circulating biomarkers and 11 measures of cognitive performance in 161 older participants recruited to undergo a six-months training intervention. For network construction, we applied coefficient of determination (R 2 ) that was calculated for all possible pairs of variables (N = 33) in four groups (CMVmen and women; CMV + men and women). Network topology has been evaluated by clustering coefficient (CC) and characteristic path length (CPL) as well as local (Elocal) and global (Eglobal) efficiency, showing the degree of network segregation (CC and Elocal) and integration (CPL and Eglobal). We found that networks under consideration showed small-world networks properties with more random characteristics. Mean CC, as well as local and global efficiency were highest and CPL shortest in CMVmales (having lowest inflammatory status and highest cognitive performance). CMVand CMV + females did not show any significant differences. Modularity analyses showed that the networks exhibit in all cases highly differentiated modular organization (with Q-value ranged between 0.397 and 0.453). Conclusions: In this work, we found that segregation and integration properties of the network were notably stronger in the group with balanced inflammatory status. We were also able to confirm our previous findings that CMV-infection and sex modulate multiple circulating biomarkers and cognitive performance and that balanced inflammatory and metabolic status in elderly contributes to better cognitive functioning. Thus, network analyses provide a useful strategy for visualization and quantitative description of multiple interactions between various circulating pro-and anti-inflammatory biomarkers, hormones, neurotrophic and metabolic factors, immune cells, and measures of cognitive performance and can be in general applied for analyzing interactions between different physiological systems.

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Section: Discussionmentioning

confidence: 99%

Network Topology Dynamics of Circulating Biomarkers and Cognitive Performance in Older Cytomegalovirus-seropositive or -seronegative Men and Women

Benedetto

Müller

Rauskolb

et al. 2019

Preprint

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“…Ageing is associated with the up-regulation of the inflammatory responses caused by chronic antigenic stress and dysregulation of cytokine secretion, increased serum levels of pro-inflammatory cytokines, e.g. IL-1, IL-6 and TNF, increased level of C reactive protein and soluble cytokine receptors [13][14][15][16][17]. The ageing process is also accompanied by chronic oxidative stress which can cause serious damage of cells, counteracted by the endogenous defense system consisted of enzymatic antioxidants, i.e.…”

Section: Introductionmentioning

confidence: 99%

NKT-like cells reveal higher than T lymphocytes expression of cellular protective proteins HSP70 and SOD2 and comparably increased expression of SIRT1 in the oldest seniors

Kaszubowska

Foerster

Kwiatkowski

et al. 2019

Folia Histochem Cytobiol.

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Introduction. NKT-like cells are "non-classical", "CD1d-independent" NKT cells which represent highly differentiated, conventional T lymphocytes coexpressing several NK (natural killer) associated receptors. They are effector lymphocytes of both innate and adaptive immunity and simultaneously regulatory cells of the adaptive immune system. They reveal large granular lymphocyte morphology and can mediate both MHC-restricted and MHC-unrestricted cytotoxicity, secrete many cytokines and modulate Th1 immune responses. The aim of our study was to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in NKT-like cells compared to T lymphocytes during ageing. Material and methods. The study involved three groups of participants: the oldest seniors (n = 25; aged over 85; mean age 88 ± 0.5 ys), the old (n = 30; aged under 85; mean age 76 ± 0.9 ys) and the young (n = 32; mean age 21 ± 0.3 ys). Whole blood samples were analyzed by flow cytometry to assess NKT-like (CD3+CD56+) and T (CD3+) cell populations. Results. The group of the oldest seniors differed from the other age groups by much higher percentage of both NKT-like cells and T lymphocytes expressing SIRT1, HSP70 and SOD2. The expression of these proteins correlated positively with the age of the participants. Interestingly, the significantly higher expression of the studied protective proteins; i.e. HSP70 and SOD2 was found in CD3+CD56+ cells compared to CD3+ lymphocytes and this phenomenon concerned all the studied age groups. These differences were not significant regarding the expression of SIRT1; however, the same tendency was noticeable. Conclusions. The analysis of CD3+ and CD3+CD56+ lymphocytes showed the increase in the number of NKT-like cells and decreased number of T cells in the process of ageing. The increased expression of cellular protective proteins SIRT1, HSP70 and SOD2 in NKT-like and T-lymphocytes of the oldest seniors seems to correspond to longevity and the observed correlations may suggest the involvement of these proteins in establishing cellular homeostasis specific for healthy ageing. Furthermore, the higher expression of the protective proteins in NKT-like cells compared to T lymphocytes may indicate their particular role in the interplay between innate and adaptive immunity responses during the process of ageing.

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“…LTL correlates with several aging-related syndromes [ 7 ]. An increasing low-grade chronic inflammatory status, reflected by an altered plasma level of multiple inflammatory mediators [ 8 – 10 ], is another hallmark of aging. Levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) continuously rise with age, and have been associated with several aging-related syndromes [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

The impact of adjuvant chemotherapy in older breast cancer patients on clinical and biological aging parameters

et al. 2016

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PurposeThis prospective observational study aimed to evaluate the impact of adjuvant chemotherapy on biological and clinical markers of aging and frailty.MethodsWomen ≥ 70 years old with early breast cancer were enrolled after surgery and assigned to a chemotherapy (Docetaxel and Cyclophosphamide) group (CTG, n=57) or control group (CG, n=52) depending on their planned adjuvant treatment. Full geriatric assessment (GA) and Quality of Life (QoL) were evaluated at inclusion (T0), after 3 months (T1) and at 1 year (T2). Blood samples were collected to measure leukocyte telomere length (LTL), levels of interleukin-6 (IL-6) and other circulating markers potentially informative for aging and frailty: Interleukin-10 (IL-10), Tumor Necrosis Factor Alpha (TNF-α), Insulin-like Growth Factor 1 (IGF-1), Monocyte Chemotactic Protein 1 (MCP-1) and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES).ResultsLTL decreased significantly but comparably in both groups, whereas IL-6 was unchanged at T2. However, IL-10, TNF-α, IGF-1 and MCP-1 suggested a minor biological aging effect of chemotherapy. Clinical frailty and QoL decreased at T1 in the CTG, but recovered at T2, while remaining stable in the CG.ConclusionChemotherapy (TC) is unlikely to amplify clinical aging or induce frailty at 1 year. Accordingly, there is no impact on the most established aging biomarkers (LTL, IL-6).

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As we age: Does slippage of quality control in the immune system lead to collateral damage?

Cited by 47 publications

References 93 publications

Network Topology Dynamics of Circulating Biomarkers and Cognitive Performance in Older Cytomegalovirus-seropositive or -seronegative Men and Women

Network Topology Dynamics of Circulating Biomarkers and Cognitive Performance in Older Cytomegalovirus-seropositive or -seronegative Men and Women

NKT-like cells reveal higher than T lymphocytes expression of cellular protective proteins HSP70 and SOD2 and comparably increased expression of SIRT1 in the oldest seniors

The impact of adjuvant chemotherapy in older breast cancer patients on clinical and biological aging parameters

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