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Characterization of the plasma proteomic profile of frailty phenotype

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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 aptamer-based 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 (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 non-frail 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.

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Data availability

Access to proteomic data is available upon review and subsequent approval of proposals submitted through the InCHIANTI study website (inchiantistudy.net).

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Funding

“The InCHIANTI study baseline” (1998–2000) was supported as a “targeted project” (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001–2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004–2010) were financed by the U.S. National Institute on Aging (Contract: N01-AG-5-0002);supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland.

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Author notes

  1. Kristina Landino and Toshiko Tanaka contributed equally to this work.

Authors and Affiliations

  1. Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, 21224, USA

    Kristina Landino, Toshiko Tanaka & Luigi Ferrucci

  2. National Institute on Aging, Intramural Research Program, Clinical Research Core, NIH, Baltimore, MD, 21224, USA

    Giovanna Fantoni

  3. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, 20892, USA

    Julián Candia

  4. Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy

    Stefania Bandinelli

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  1. Kristina Landino
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  2. Toshiko Tanaka
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  4. Julián Candia
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Correspondence to Toshiko Tanaka.

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Landino, K., Tanaka, T., Fantoni, G. et al. Characterization of the plasma proteomic profile of frailty phenotype. GeroScience 43, 1029–1037 (2021). https://doi.org/10.1007/s11357-020-00288-9

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