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High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

ABSTRACT: Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors.In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25-40 yrs)].Associations between age and 9 immune signaling responses identified in the previously published 60 donor cohort were confirmed in the current study. Furthermore, within the current study cohort, 48 additional immune signaling responses differed significantly between young and elderly donors. These associations spanned all profiled modulators and immune cell subsets.These results demonstrate that SCNP, a systems-based approach, can capture the complexity of the cellular mechanisms underlying immunological aging. Further, the confirmation of age associations in an independent donor cohort supports the use of SCNP as a tool for identifying reproducible predictive biomarkers in areas such as vaccine response and response to cancer immunotherapies.

SUBMITTER: Longo DM

PROVIDER: S-EPMC4229969 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

Longo Diane M DM Louie Brent B Ptacek Jason J Friedland Greg G Evensen Erik E Putta Santosh S Atallah Michelle M Spellmeyer David D Wang Ena E Pos Zoltan Z Marincola Francesco M FM Schaeffer Andrea A Lukac Suzanne S Railkar Radha R Beals Chan R CR Cesano Alessandra A Carayannopoulos Leonidas N LN Hawtin Rachael E RE

Journal of translational medicine 20140621

<h4>Background</h4>Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors.<h4>Methods</h4>In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an i ...[more]

PMID: 24952610

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Project description:IntroductionSuccessful inhibition of distracting emotions is important for preserving well-being and daily functioning. There is conflicting evidence regarding the impact of healthy aging on emotional inhibition, and possible age-related alterations in the neuronal underpinnings of emotional interference processing are unexplored.MethodsThirty younger (mean age 26 years; 15 women) and 30 older (mean age 71 years; 13 women) healthy adults performed a face-word emotional Stroop task while undergoing functional magnetic resonance imaging of the brain. A resting-state scan was acquired for calculating the amplitude of low-frequency fluctuations as an estimate of vascular reactivity. Comparisons of brain activation during the task were assessed in a whole-brain, voxel-wise analysis, contrasting congruent, and incongruent conditions. The canonical regions of the frontoparietal, salience, dorsal attention, and default mode networks were used as seed regions for assessing functional connectivity within and between large-scale brain networks. Task performance was evaluated using response accuracy and response time.ResultsThe older adults had longer response times and lower task accuracy than the younger adults, but the emotional interference effect was not significantly different between the groups. Whole-brain analysis revealed no significant age-related differences in brain activation patterns. Rescaling the data for estimated variability in vascular reactivity did not affect the results. In older adults, there was relatively stronger functional connectivity with the default mode network, the sensorimotor network, and the dorsal attention network for the frontoparietal and salience network seeds during the task. Conversely, younger adults had relatively stronger connections within and between the frontoparietal and salience networks.ConclusionIn this first fMRI study of emotional Stroop interference in older and younger adults, we found that the emotional interference effect was unchanged in healthy aging and replicated the finding from non-emotional task studies that older adults have greater between-network and less within-network connectivity compared to younger adults.

Dataset Information

High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

Publications

High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

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