CTRP9 ameliorates cellular senescence via PGC1α/AMPK signaling in mesenchymal stem cells

Stroke is the second most common cause of death worldwide, and thus, it imposes great financial burdens on both individuals and society. Mesenchymal stem cell (MSC) therapy is a promising approach for ischemic brain injury. However, MSC treatment potential is progressively reduced with age, limiting their therapeutic efficacy for brain repair poststroke. C1q and tumor necrosis factorrelated protein 9 (CTRP9) is a novel cytoprotective cytokine with antioxidant effects, which is highly expressed in brain tissue. The present study tested the hypothesis that CTRP9 might act as an antisenescence factor to promote the rejuvenation of aged MSCs. MSCs were isolated from the bone marrow of young (8weeksold) and aged (18monthsold) male C57BL/6 mice. Cell proliferation was measured by Cell Counting Kit8 assay and cell viability was determined by MTT assay. Gene expression levels of interleukin (IL)6 and IL10 were evaluated with reverse transcriptionquantitative polymerase chain reaction, and secretion of vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, and insulinlike growth factor were measured by ELISA. The expression levels of proteins in the peroxisome proliferatoractivated receptor γcoactivator (PGC)1α/AMPactivated protein kinase (AMPK) signaling pathway were investigated with western blotting. Oxidative stress was evaluated by detecting mitochondrial membrane potential, reactive oxygen species, superoxide dismutase activity and malondialdehyde. MSCs isolated from aged mice exhibited reduced proliferation and viability, and impaired immunoregulatory and paracrine abilities, compared with MSCs from younger mice. CTRP9 had a significant antisenescence effect in aged MSCs by activating PGC1α/AMPK signaling and decreasing the oxidative response. Silencing either PGC1α or AMPK abolished the above effects of CTRP9. These results suggest that CTRP9 may have a critical role in cellular senescence by facilitating stem cell rejuvenation, and may therefore have the potential to enhance the efficacy of stem cell therapy.