HuR coordinates systemic aging through platelet infiltration.

Here, we uncover a central role of platelets in systemic aging. In aged mice, the levels of platelet-secreted pro-inflammatory factors (PSPF) increased greatly in the serum and platelets, leading to a diffuse increase of platelet infiltration in brain, liver, lung, kidney, and aortic root.

The RNA-binding protein HuR/ELAVL1, a major regulator of RNA metabolism, promoted the production of PSPF in platelets. Platelet-specific deletion of HuR reduced the expression of PSPF in platelets, alleviated platelet infiltration in brain, liver, lung, kidney, and aortic root, and delayed systemic aging. By using single-nucleus sequencing, platelet-specific HuR ablation was found to alleviate p53 and pro-inflammatory signaling pathways in liver, lung, and brain tissues in aged mice.