Cross-platform proteomics signatures of extreme old age.

Autor: Reed ER; Data Intensive Study Center, Tufts University, Boston, MA, USA., Chandler KB; Center for Biomedical Mass Spectrometry, Department of Biochemistry and Cell Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Department of Cellular and Molecular Medicine, Florida International University, Miami, FL, USA., Lopez P; Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA., Costello CE; Center for Biomedical Mass Spectrometry, Department of Biochemistry and Cell Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Andersen SL; Geriatric Section, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA, USA., Perls TT; Geriatric Section, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA, USA., Li M; Division of Computational Biomedicine, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Bae H; Biostatistics Program, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA., Soerensen M; Department of Public Health, University of Southern Denmark, Odense, Denmark., Monti S; Division of Computational Biomedicine, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA., Sebastiani P; Data Intensive Study Center, Tufts University, Boston, MA, USA. psebastiani@tuftsmedicalcenter.org.; Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA. psebastiani@tuftsmedicalcenter.org.; Department of Medicine, School of Medicine, Tufts University, Boston, MA, USA. psebastiani@tuftsmedicalcenter.org.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2024 Jul 25. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1007/s11357-024-01286-x
Abstrakt: In previous work, we used a SomaLogic platform targeting approximately 5000 proteins to generate a serum protein signature of centenarians that we validated in independent studies that used the same technology. We set here to validate and possibly expand the results by profiling the serum proteome of a subset of individuals included in the original study using liquid chromatography tandem mass spectrometry (LC-MS/MS). Following pre-processing, the LC-MS/MS data provided quantification of 398 proteins, with only 266 proteins shared by both platforms. At 1% FDR statistical significance threshold, the analysis of LC-MS/MS data detected 44 proteins associated with extreme old age, including 23 of the original analysis. To identify proteins for which associations between expression and extreme-old age were conserved across platforms, we performed inter-study conservation testing of the 266 proteins quantified by both platforms using a method that accounts for the correlation between the results. From these tests, a total of 80 proteins reached 5% FDR statistical significance, and 26 of these proteins had concordant pattern of gene expression in whole blood generated in an independent set. This signature of 80 proteins points to blood coagulation, IGF signaling, extracellular matrix (ECM) organization, and complement cascade as important pathways whose protein level changes provide evidence for age-related adjustments that distinguish centenarians from younger individuals. The comparison with blood transcriptomics also highlights a possible role for neutrophil degranulation in aging.
(© 2024. The Author(s), under exclusive licence to American Aging Association.)
Databáze: MEDLINE
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