Inflammatory signatures in older persons with physical frailty and sarcopenia: The frailty “cytokinome” at its core

Emanuele Marzetti, Anna Picca, Federico Marini, Alessandra Biancolillo, Hélio José Coelho-Junior, Jacopo Gervasoni, Maurizio Bossola, Matteo Cesari, Graziano Onder, Francesco Landi, Roberto Bernabei, Riccardo Calvani

Research output: Contribution to journalArticle

Abstract

Background: The construct of physical frailty and sarcopenia (PF&S) identifies an age-related pre-disability condition defined by reduced physical performance and low muscle mass. Whether PF&S is characterized by perturbations of the cytokine network is presently unclear. Furthermore, the existence of gender-specific inflammatory profiles of PF&S is unknown. This study was designed to explore the association between a large panel of inflammatory biomolecules and PF&S in older adults through a multivariate statistical approach. Gender-specific inflammatory patterns were also explored. Methods: One-hundred community-dwellers aged 70 years and older with PF&S and 100 non-sarcopenic, non-frail controls (nonPF&S) were enrolled. A panel of 30 circulating inflammatory biomarkers was assayed. Partial least squares discriminant analysis (PLS-DA) was employed to explore the relationship between inflammatory molecules and PF&S. Separate PLS-DA models were built for the whole sample and the two genders. Double cross-validation procedures were used to validate the predictive ability of PLS-DA models. Results: The optimal complexity of the PLS-DA model built on the whole sample was found to be four latent variables. The proportion of correct classification was 75.6 ± 1.3% (82.3 ± 1.6% for enrollees with PF&S and 68.7 ± 2.5% for nonPF&S controls). The inflammatory profile of people with PF&S was defined by higher levels of P-selectin, C-reactive protein (CRP), and interferon γ-induced protein 10. NonPF&S participants were characterized by higher levels of myeloperoxidase (MPO), interleukin (IL) 8, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α, platelet-derived growth factor (PDGF) BB. Gender-specific PLS-DA allowed identifying a “core” inflammatory signature of PF&S, composed by higher levels of CRP, and lower concentrations of MPO, IL8, MCP-1, and PDGF-BB, with peculiar patterns of relationships for men and women. Conclusions: A core inflammatory profile was identified in people with PF&S with a gender-specific signature. The dissection of the PF&S “cytokinome” will provide novel insights into the role played by inflammation in the disabling cascade and allow designing personalized treatment strategies.

Original languageEnglish
Pages (from-to)129-138
Number of pages10
JournalExperimental Gerontology
Volume122
DOIs
Publication statusPublished - Jul 15 2019

Keywords

  • Aging
  • Biomarkers
  • Cytokines
  • Inflammaging
  • Multi-block partial least squares - discriminant analysis
  • Physical performance

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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