Proteome and functional decline as platelets age in the circulation

Allan, Harriet E, Hayman, Melissa A, Marcone, Simone, Chan, Melissa V, Edin, Matthew L, Maffucci, Tania, Joshi, Abhishek, Menke, Laura, Crescente, Marilena ORCID: https://orcid.org/0000-0003-3164-512X, Mayr, Manuel, Zeldin, Darryl C, Armstrong, Paul C and Warner, Timothy D (2021) Proteome and functional decline as platelets age in the circulation. Journal of Thrombosis and Haemostasis, 19 (12). pp. 3095-3112. ISSN 1538-7933

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Abstract

Background: Platelets circulate in the blood of healthy individuals for approximately 7–10 days regulated by finely balanced processes of production and destruction. As platelets are anucleate we reasoned that their protein composition would change as they age and that this change would be linked to alterations in structure and function. Objective: To isolate platelets of different ages from healthy individuals to test the hypothesis that changes in protein content cause alterations in platelet structure and function. Methods: Platelets were separated according to thiazole orange fluorescence intensity as a surrogate indicator of mRNA content and so a marker of platelet age and then subjected to proteomics, imaging, and functional assays to produce an in-depth analysis of platelet composition and function. Results: Total protein content was 45 ± 5% lower in old platelets compared to young platelets. Predictive proteomic pathway analysis identified associations with 28 biological processes, notably higher hemostasis in young platelets whilst apoptosis and senescence were higher in old platelets. Further studies confirmed platelet ageing was linked to a decrease in cytoskeletal protein and associated capability to spread and adhere, a reduction in mitochondria number, and lower calcium dynamics and granule secretion. Conclusions: Our findings demonstrate changes in protein content are linked to alterations in function as platelets age. This work delineates physical and functional changes in platelets as they age and serves as a base to examine differences associated with altered mean age of platelet populations in conditions such as immune thrombocytopenia and diabetes.