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BackgroundExercise train (ET) stimulates muscle response in pathological conditions, including aging. The molecular mechanisms by which exercise improves impaired adiponectin/adiponectin receptor 1 (AdipoR1)‐related muscle actions associated with aging are poorly understood. Here we observed that in a senescence‐accelerated mouse prone 10 (SAMP10) model, long‐term ET modulated muscle‐regenerative actions.Methods25‐week‐old male SAMP10 mice were randomly assigned to the control and the ET (45 min/time, 3/week) groups for 4 months. Mice that were maintained in a sedentary condition served controls.ResultsET ameliorated aging‐related muscle changes in microstructure, mitochondria, and performance. The amounts of proteins or mRNAs for p‐AMPKα, p‐Akt, p‐ERK1/2, p‐mTOR, Bcl‐XL, p‐FoxO3, peroxisome proliferators‐activated receptor‐γ coactivator, adiponectin receptor1 (adpoR1), and cytochrome c oxidase‐IV, and the numbers of CD34+/integrin‐α7 + muscle stem cells (MuSCs) and proliferating cells in the muscles and bone‐marrow were enhanced by ET, whereas the levels of p‐GSK‐3α and gp91phox proteins and apoptotic cells were reduced by ET. The ET also resulted in increased levels of plasma adiponectin and the numbers of bone‐marrow (BM)‐derived circulating CD34+/integrin‐α7 + MuSCs and their functions. Integrin‐α7 + MuSCs of exercised mice had improved changes of those beneficial molecules. These ET‐mediated aged muscle benefits were diminished by adiponectin and AdipoR1 blocking as well as AMPK inhibition. Finally, recombinant mouse adiponectin enhanced AMPK and mTOR phosphorylations in BM‐derived integrin‐α7 + cells.ConclusionsThese findings suggest that ET can improve aging‐related impairments of BM‐derived MuSC regenerative capacity and muscle metabolic alterations via an AMPK‐dependent mechanism that is mediated by an adiponectin/AdipoR1 axis in SAMP10 mice.

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BackgroundExposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Given that dipeptidyl peptidase‐4 (DPP4) regulates several intracellular signaling pathways associated with the glucagon‐like peptide‐1 (GLP‐1) metabolism, we investigated the role of DPP4/GLP‐1 axis in vascular senescence and ischemia‐induced neovascularization in mice under chronic stress, with a special focus on adiponectin ‐mediated peroxisome proliferator activated receptor‐γ/its co‐activator 1α (PGC‐1α) activation.Methods and ResultsSeven‐week‐old mice subjected to restraint stress for 4 weeks underwent ischemic surgery and were kept under immobilization stress conditions. Mice that underwent ischemic surgery alone served as controls. We demonstrated that stress impaired the recovery of the ischemic/normal blood‐flow ratio throughout the follow‐up period and capillary formation. On postoperative day 4, stressed mice showed the following: increased levels of plasma and ischemic muscle DPP4 and decreased levels of GLP‐1 and adiponectin in plasma and phospho‐AMP‐activated protein kinase α (p‐AMPKα), vascular endothelial growth factor, peroxisome proliferator activated receptor‐γ, PGC‐1α, and Sirt1 proteins and insulin receptor 1 and glucose transporter 4 genes in the ischemic tissues, vessels, and/or adipose tissues and numbers of circulating endothelial CD31+/c‐Kit+ progenitor cells. Chronic stress accelerated aortic senescence and impaired aortic endothelial sprouting. DPP4 inhibition and GLP‐1 receptor activation improved these changes; these benefits were abrogated by adiponectin blocking and genetic depletion.ConclusionsThese results indicate that the DPP4/GLP‐1‐adiponectin axis is a novel therapeutic target for the treatment of vascular aging and cardiovascular disease under chronic stress conditions.