Objective   Our study aimed to assess the effects of Growth and differentiation factor 11 (GDF11) on the function of endothelial progenitor cells in middle-age individuals (EPCs-MA) isolated from mouse bone marrow and to explore the mechanistic relationship between GDF11 and age-related ALP impairment.   Methods   Bone marrow-derived EPCs were isolated, culture and GDF11 treatment. In vivo, the mice model of myocardial ischemia (MI) was induced by permanent ligation of the left anterior descending coronary artery (LAD) and mice were randomly divided into MI group and EPCs transplantation group (EPCs-Y, EPCs-MA, EPCs-MA/GDF11). The positive effect of GDF11 treatment of EPCs-MA on MI was verified by echocardiography and the average ratio of fibrotic area to left ventricular (LV) area. In vitro, the effect of GDF11 on ameliorating EPCs aging by promoting autophagy was confirmed by transwell assay, immunofluorescence staining, characterization of EPCs ultrastructure through transmission electron microscope (TEM), lysosome imaging and Western blot.   Result   Our findings demonstrate that GDF11 enhances the migration capacity of EPCs-MA and improves recovery of impaired cardiac function after myocardial infarction (MI) in mice, with EPCs isolated from young mice (EPCs-Y) as controls. Moreover, GDF11 restored functional phenotypes of EPCs-MA to levels akin to EPCs-Y, promoting the expression of CD31, endogenous NO synthase, and the restoration of von Willebrand factor (vWF) and CDH5 expression patterns, as well as the formation of Weibel-Palade bodies—key organelles for storage and secretion in endothelial cells and EPCs. Furthermore, GDF11 significantly enhanced the autophagic clearance capability of EPCs-MA by promoting ALP.   Conclusions   Our results suggest that GDF11 ameliorates cardiac function impairment by restoring the activities of EPCs from aging mice through enhanced ALP. These findings suggest that GDF11 may hold therapeutic potential for improving aging-related conditions associated with declined autophagy.

Acute liver injury (ALI) is characterized by apoptosis, inflammation, and oxidative stress, and pathogenic mechanism of ALI is poorly understood. Apoptosis-stimulating of p53 protein 1 (ASPP1) is involved in environmental responses, tumor growth, and NF-_KB activity, which is of critical importance to ALI. However, the role of ASPP1 in ALI remains largely unexplored. The current study aimed to determine the role of ASPP1 in ALI induced by CCl4 and the underlying mechanism. ASPP1 expression was detected in wild type (WT) mice with ALI induced by CCl4. The function of ASPP1 in ALI induced by CCl4 was investigated using conventional knockout ASPP1 mice. ASPP1 expression significantly increased in ALI mice at 24 hours after CCl4 injection. Deletion of ASSP1 ameliorated apoptosis, inflammation, and necrosis in ALI relative to WT mice. In addition, deficiency of ASPP1 improved liver flood flow as well as ALT and AST levels. The levels of phosphorylated p65 and phosphorylated IκBα were lower in ASPP1-/- mice than in WT mice with ALI. These results implicate that deletion of ASPP1 may act via inhibition of the NF-кB pathway and protect mice from ALI, which may be a new potential therapeutic target for the treatment of ALI.