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Plasma proteomic profile of frailty.

ABSTRACT: Frailty is a state of decreased physiological reserve and increased vulnerability to adverse outcomes in aging, and is characterized by dysregulation across various biological pathways. Frailty may manifest biologically as alteration in protein expression, possibly regulated at genetic, transcriptional and epigenetic levels. In this study, we examined the proteomic profile associated with frailty defined by an established cumulative frailty index (FI). Using the SomaScan® assay, 4265 proteins were measured in plasma, of which 55 were positively associated and 88 were negatively associated with the FI. The proteins most strongly associated with frailty were fatty acid-binding proteins, including fatty acid-binding protein (FABP) (p = 1.96 × 10-19 ) and FABPA (p = 8.10 × 10-16 ), leptin (p = 1.43 × 10-14 ), and ANTR2 (p = 7.95 × 10-20 ). Pathway analysis with the top 143 frailty-associated proteins revealed enrichment for proteins in pathways related to lipid metabolism, musculoskeletal development and function, cell-to-cell signaling and interaction, cellular assembly, and organization. Frailty prediction model constructed with elastic net regression utilizing 110 proteins demonstrated a correlation between predicted frailty and observed frailty (r = 0.57, p < 2.2 × 10-16 ). Predicted frailty was also more strongly correlated with chronological age (r = 0.54, p < 2.2 × 10-16 ) than observed frailty (r = 0.37, p = 1.2 × 10-15 ). This study identified novel proteins and pathways related to frailty that may offer improved frailty phenotyping and prediction.

SUBMITTER: Sathyan S

PROVIDER: S-EPMC7511877 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Plasma proteomic profile of frailty.

Sathyan Sanish S Ayers Emmeline E Gao Tina T Milman Sofiya S Barzilai Nir N Verghese Joe J

Aging cell 20200806 9

Frailty is a state of decreased physiological reserve and increased vulnerability to adverse outcomes in aging, and is characterized by dysregulation across various biological pathways. Frailty may manifest biologically as alteration in protein expression, possibly regulated at genetic, transcriptional and epigenetic levels. In this study, we examined the proteomic profile associated with frailty defined by an established cumulative frailty index (FI). Using the SomaScan<sup>®</sup> assay, 4265 ...[more]

PMID: 32762010

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Project description:Proteomic approaches have unique advantages in the identification of biological pathways that influence physical frailty, a multifactorial geriatric syndrome predictive of adverse health outcomes in older adults. To date, proteomic studies of frailty are scarce, and few evaluated prefrailty as a separate state or examined predictors of incident frailty. Using plasma proteins measured by 4955 SOMAmers in the Atherosclerosis Risk in Community study, we identified 134 and 179 proteins cross-sectionally associated with prefrailty and frailty, respectively, after Bonferroni correction (p < 1 × 10-5 ) among 3838 older adults aged ≥65 years, adjusting for demographic and physiologic factors and chronic diseases. Among them, 23 (17%) and 82 (46%) were replicated in the Cardiovascular Health Study using the same models (FDR p < 0.05). Notably, higher odds of prefrailty and frailty were observed with higher levels of growth differentiation factor 15 (GDF15; pprefrailty = 1 × 10-15 , pfrailty = 2 × 10-19 ), transgelin (TAGLN; pprefrailty = 2 × 10-12 , pfrailty = 6 × 10-22 ), and insulin-like growth factor-binding protein 2 (IGFBP2; pprefrailty = 5 × 10-15 , pfrailty = 1 × 10-15 ) and with a lower level of growth hormone receptor (GHR, pprefrailty = 3 × 10-16 , pfrailty = 2 × 10-18 ). Longitudinally, we identified 4 proteins associated with incident frailty (p < 1 × 10-5 ). Higher levels of triggering receptor expressed on myeloid cells 1 (TREM1), TAGLN, and heart and adipocyte fatty-acid binding proteins predicted incident frailty. Differentially regulated proteins were enriched in pathways and upstream regulators related to lipid metabolism, angiogenesis, inflammation, and cell senescence. Our findings provide a set of plasma proteins and biological mechanisms that were dysregulated in both the prodromal and the clinical stage of frailty, offering new insights into frailty etiology and targets for intervention.

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Plasma proteomic profile of frailty.

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Plasma proteomic profile of frailty.

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