The evolving role of platelets in aging and cancer progression

Platelets, once considered solely for their roles in hemostasis and thrombosis, are now recognized as pivotal players in the aging process and cancer progression. Aging reprograms the platelet compartment at multiple levels, including reduced counts, structural alterations, shifts in transcriptomic and proteomic profiles, fostering a hyperactive and pro-inflammatory state termed thromboinflammation. Platelets not only contribute to age-related cardiovascular and inflammatory disorders but also are involved in tumorigenesis. In the circulation, platelets bind to circulating tumor cells and form a physical barrier that protects them from immune destruction. Within the tumor microenvironment, platelets subsequently facilitate cancer progression by orchestrating angiogenesis, enhancing metastatic dissemination, and suppressing anti-tumor immunity. Platelets also give rise to tumor-educated platelets (TEPs) that carry diagnostic molecular signatures. This review systematically delineates the dynamic functions of platelets in aging and in cancer, with a brief discussion on the potential link between aged platelets and cancer progression. We also discuss the potential value and future directions of platelet-targeted therapeutic strategies in the prevention and treatment of age-related cancers.