Emanuele Marzetti1, Anna Picca2, Federico Marini3, Alessandra Biancolillo3, Hélio José Coelho-Junior4, Jacopo Gervasoni5, Maurizio Bossola5, Matteo Cesari6, Graziano Onder5, Francesco Landi5, Roberto Bernabei7, Riccardo Calvani5. 1. Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy. 2. Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address: anna.picca1@gmail.com. 3. Department of Chemistry, Sapienza Università di Roma, Rome, Italy. 4. Università Cattolica del Sacro Cuore, Rome, Italy; Applied Kinesiology Laboratory-LCA, School of Physical Education, Universidade Estadual de Campinas, Campinas, SP, Brazil. 5. Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy. 6. Department of Clinical Sciences and Community Health, Università di Milano, Milan, Italy; Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 7. Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address: roberto.bernabei@unicatt.it.
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.
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.
Authors: Hélio José Coelho-Júnior; Marco Carlos Uchida; Anna Picca; Roberto Bernabei; Francesco Landi; Riccardo Calvani; Matteo Cesari; Emanuele Marzetti Journal: Aging Clin Exp Res Date: 2021-02-15 Impact factor: 3.636