Identification of biomarkers for physical frailty and sarcopenia through a new multi-marker approach: results from the BIOSPHERE study
- 1 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in GeroScience
- Vol. 43 (2), 727-740
- https://doi.org/10.1007/s11357-020-00197-x
Abstract
Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The aim of the present study was to provide an initial selection of biomarkers for PF&S using a novel multivariate analytic strategy. Two-hundred community-dwellers, 100 with PF&S and 100 non-physically frail, non-sarcopenic (nonPF&S) controls aged 70 and older were enrolled as part of the BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons (BIOSPHERE) study. A panel of 74 serum analytes involved in inflammation, muscle growth and remodeling, neuromuscular junction damage, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel) analysis. Separate SO-CovSel models were constructed for the whole study population and for the two genders. The model with the best prediction ability obtained with the smallest number of variables was built using seven biomolecules. This model allowed correct classification of 80.6 ± 5.3% PF&S participants and 79.9 ± 5.1% nonPF&S controls. The PF&S biomarker profile was characterized by higher serum levels of asparagine, aspartic acid, and citrulline. Higher serum concentrations of platelet-derived growth factor BB, heat shock protein 72 (Hsp72), myeloperoxidase, and α-aminobutyric acid defined the profile of nonPF&S participants. Gender-specific SO-CovSel models identified a “core” biomarker profile of PF&S, characterized by higher serum levels of aspartic acid and Hsp72 and lower concentrations of macrophage inflammatory protein 1β, with peculiar signatures in men and women. SO-CovSel analysis allowed identifying a set of potential biomarkers for PF&S. The adoption of such an innovative multivariate approach could help address the complex pathophysiology of PF&S, translate biomarker discovery from bench to bedside, and unveil novel targets for interventions.Keywords
Funding Information
- Fondazione Roma (NCDs Call for Proposals 2013)
- Innovative Medicines Initiative (115621)
- Centro Studi Achille e Linda Lorenzon (N/A)
- Università Cattolica del Sacro Cuore (D3.2 2013, D3.2 2015)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (001)
This publication has 97 references indexed in Scilit:
- The Hallmarks of AgingCell, 2013
- Plasma heat shock protein 72 as a biomarker of sarcopenia in elderly peopleCell Stress and Chaperones, 2012
- Age-related changes in serum amino acids concentrations in healthy individualscclm, 2012
- Effects of leucine and citrulline versus non-essential amino acids on muscle protein synthesis in fasted rat: a common activation pathway?Amino Acids, 2011
- Systems biology of ageing and longevityPhilosophical Transactions B, 2011
- Circulating Fibroblast Growth Factor-21 Is Elevated in Impaired Glucose Tolerance and Type 2 Diabetes and Correlates With Muscle and Hepatic Insulin ResistanceDiabetes Care, 2009
- CC family chemokines directly regulate myoblast responses to skeletal muscle injuryJournal Of Physiology-London, 2008
- Role of platelet-derived growth factors in physiology and medicineGenes & Development, 2008
- HSP72 protects against obesity-induced insulin resistanceProceedings of the National Academy of Sciences of the United States of America, 2008
- Serum amino acid concentrations in aging men and womenAmino Acids, 2003