Platelet response to influenza vaccination reflects effects of aging

Author:

Konstorum Anna1ORCID,Mohanty Subhasis2,Zhao Yujiao3,Melillo Anthony1,Vander Wyk Brent4,Nelson Allison2,Tsang Sui4,Blevins Tamara P.5,Belshe Robert B.5,Chawla Daniel G.6,Rondina Matthew T.78,Gill Thomas M.4,Montgomery Ruth R.3,Allore Heather G.4,Kleinstein Steven H.16,Shaw Albert C.2

Affiliation:

1. Department of Pathology Yale School of Medicine New Haven Connecticut USA

2. Department of Internal Medicine, Section of Infectious Diseases Yale School of Medicine New Haven Connecticut USA

3. Section of Rheumatology, Department of Internal Medicine Yale School of Medicine New Haven Connecticut USA

4. Department of Internal Medicine, Section of Geriatrics and Program on Aging Yale School of Medicine New Haven Connecticut USA

5. Division of Infectious Diseases, Department of Medicine Saint Louis University School of Medicine St. Louis Missouri USA

6. Program in Computational Biology and Bioinformatics Yale University New Haven Connecticut USA

7. Departments of Internal Medicine and Pathology, and the Molecular Medicine Program University of Utah Health Salt Lake City Utah USA

8. Department of Medicine and the GRECC George E. Wahlen VAMC Salt Lake City Utah USA

Abstract

AbstractPlatelets 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.

Funder

National Institute of Allergy and Infectious Diseases

National Institute on Aging

Publisher

Wiley

Subject

Cell Biology,Aging

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