IGFBP7 promotes cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, and Igfbp7 deficiency or inhibition attenuates cardiac dysfunction in a pressure overload mouse HF model, suggesting that therapeutic targeting of IGFBP7 might be promising for the treatment of HF. Here, IGF1R is linked to hydrops fetalis.