Characterization of the plasma proteomic profile of frailty phenotype
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ORIGINAL ARTICLE
Characterization of the plasma proteomic profile of frailty phenotype Kristina Landino & Toshiko Tanaka & Giovanna Fantoni & Julián Candia & Stefania Bandinelli & Luigi Ferrucci
Received: 5 August 2020 / Accepted: 14 October 2020 # This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract Frailty is a risk factor for poor health outcomes in older adults. The aim of this study was to identify plasma proteomic biomarkers of frailty in 752 men and women older than 65 years of age from the InCHIANTI study. One thousand three hundred one plasma proteins were measured using an aptamerbased assay. Associations of each protein with frailty status were assessed using logistic regression and four proteins creatine kinase M-type (CKM), B-type (CKB), C-X-C motif chemokine ligand 13 (CXCL13), and thrombospondin 2 (THBS2) were associated with frailty status. Two proteins, cyclin-dependent kinase 5
Kristina Landino and Toshiko Tanaka contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11357-020-00288-9) contains supplementary material, which is available to authorized users. K. Landino : T. Tanaka (*) : L. Ferrucci Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA e-mail: [email protected] G. Fantoni National Institute on Aging, Intramural Research Program, Clinical Research Core, NIH, Baltimore, MD 21224, USA J. Candia Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA S. Bandinelli Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy
(CDK5/CDK5R1) and interleukin 1 alpha (IL1A), were associated with worsening of frailty status over time in volunteers free of frailty at baseline. Using partial least squares discriminant analysis (PLS-DA), data of 1301 proteins was able to discriminate between frail and nonfrail with a 2% error rate. The proteins with greater discriminatory ability represented the inflammation, blood coagulation, and cell growth pathways. The utility of these proteins as biomarkers of frailty should be further explored. Keywords Proteomics . Aging . Frailty . Inflammation
Introduction Frailty is a geriatric syndrome that results from functional declines in multiple biological and physiological systems and that manifests itself as a vulnerable state characterized by sharp decline in health and functional status in response to minor stressors [1]. Several operational definitions of frailty have been proposed, including one by Fried and colleagues based on five criteria: poor grip strength, poor walking ability, unintentional weight loss, exhaustion, and low physical ability [2]. The presence of three or more of these criteria was defined as frailty and having one or two of these criteria was defined as “pre-frailty.” Fried and collaborators demonstrated that the prevalence of both pre-frailty and frailty increases with ag
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