Platelet response to influenza vaccination reflects effects of aging

Abstract

Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity. However, how age and geriatric conditions such as frailty influence platelet function during an immune response remains unclear. We assessed the platelet transcriptome at baseline and following influenza vaccination in Younger (age 21–35) and Older (age ≥65) adults (including community‐dwelling individuals who were largely non‐frail and skilled nursing facility (SNF)‐resident adults who nearly all met criteria for frailty). Prior to vaccination, we observed an age‐associated increase in the expression of platelet activation and mitochondrial RNAs and decrease in RNAs encoding proteins mediating translation. Age‐associated differences were also identified in post‐vaccination response trajectories over 28 days. Using tensor decomposition analysis, we found increasing RNA expression of genes in platelet activation pathways in young participants, but decreasing levels in (SNF)‐resident adults. Translation RNA trajectories were inversely correlated with these activation pathways. Enhanced platelet activation was found in community‐dwelling older adults at the protein level, compared to young individuals both prior to and post‐vaccination; whereas SNF residents showed decreased platelet activation compared to community‐dwelling older adults that could reflect the influence of decreased translation RNA expression. Our results reveal alterations in the platelet transcriptome and activation responses that may contribute to age‐associated chronic inflammation and the increased incidence of thrombotic and pro‐inflammatory diseases in older adults.

Abstract

Platelets mediate innate immune responses as well as thrombosis. We found an age‐associated increase in platelet activation RNAs, further increased in skilled nursing facility (enriched for frailty) vs. community‐dwelling (largely non‐frail) older adults. Tensor decomposition analysis revealed distinct trajectories of platelet activation following high‐dose influenza vaccine. Our results implicate platelets, which are anucleate and lack nuclear transcription, in age‐related chronic inflammation.