Age Increases Platelet Aggregation and Alters the Platelet Transcriptome in Healthy Adults

Introduction: Age is the strongest risk factor for cardiovascular diseases (CVD). Platelets contribute to CVD pathogenesis and may mediate, in part, the association between age and CVD. In this study, we investigated the impact of aging on platelet activity responses and the platelet transcriptome. Hypothesis: Increasing age is associated with increased platelet aggregation and altered transcriptome. Method: Adults ≥ 18 years without CVD, off aspirin or NSAIDS were stratified by age tertiles. Platelet activity was measured by flow cytometry and light transmission aggregometry in response to submaximal agonist stimulation with ADP, AA, collagen, and epinephrine. The association between age and platelet variables were adjusted for sex, race/ethnicity, BMI, hypertension, and diabetes. Differentially expressed transcripts by age were identified using the limma package, adjusted for sex and race/ethnicity. Results: Among 151 participants, median age was 52 years (IQR 38 to 61), 87 (58%) were female, 75 (50%) were non-White, and 27 (18%) were Hispanic. There was no association between platelet count and size with age. There was a significant association between platelet aggregation in response to multiple agonists and age in both unadjusted and adjusted analyses ( Table ). Using a general linear model, we identified 199 platelet transcripts significantly affected by age (P <0.01, 119-positively, 80-negatively). Gene set enrichment analysis demonstrated upregulation of platelet activity pathways (platelet alpha granule [NES = 2.09, q = 0.0008], platelet activation [NES = 1.90, q = 0.002), and platelet aggregation [NES = 1.77, q = 0.03]) with increasing age. Conclusion: Age is independently associated with platelet aggregation in response to submaximal agonist stimulation, a finding supported by the enrichment of platelet activation pathways in the transcriptome. Future studies are needed to elucidate the mechanisms by which age increases platelet aggregation.