TNF-α-driven inflammation and mitochondrial dysfunction define the platelet hyperreactivity of aging.

ABSTRACT: Aging and chronic inflammation are independent risk factors for the development of atherothrombosis and cardiovascular disease. We hypothesized that aging-associated inflammation promotes the development of platelet hyperreactivity and increases thrombotic risk during aging. Functional platelet studies in aged-frail adults and old mice demonstrated that their platelets are hyperreactive and form larger thrombi. We identified tumor necrosis factor α (TNF-α) as the key aging-associated proinflammatory cytokine responsible for platelet hyperreactivity. We further showed that platelet hyperreactivity is neutralized by abrogating signaling through TNF-α receptors in vivo in a mouse model of aging. Analysis of the bone marrow compartments showed significant platelet-biased hematopoiesis in old m

SUBMITTER: Davizon-Castillo P 

PROVIDER: S-EPMC6716075 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature