title: High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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)].
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Diane M
authors: DM
authors: Longo
authors: Brent
authors: B
authors: Louie
authors: Jason
authors: J
authors: Ptacek
authors: Greg
authors: G
authors: Friedland
authors: Erik
authors: E
authors: Evensen
authors: Santosh
authors: S
authors: Putta
authors: Michelle
authors: M
authors: Atallah
authors: David
authors: D
authors: Spellmeyer
authors: Ena
authors: E
authors: Wang
authors: Zoltan
authors: Z
authors: Pos
authors: Francesco M
authors: FM
authors: Marincola
authors: Andrea
authors: A
authors: Schaeffer
authors: Suzanne
authors: S
authors: Lukac
authors: Radha
authors: R
authors: Railkar
authors: Chan R
authors: CR
authors: Beals
authors: Alessandra
authors: A
authors: Cesano
authors: Leonidas N
authors: LN
authors: Carayannopoulos
authors: Nodality, South San Francisco, CA 94080, USA. rachael.hawtin@nodality.com.
authors: Rachael E
authors: RE
authors: Hawtin
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D015331:Cohort Studies; D064368:Healthy Volunteers; D006801:Humans; D015398:Signal Transduction