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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Atherosclerotic cardiovascular disease (ASCVD) is an inflammatory disease characterized by extensive arterial wall matrix protein degradation. Cysteine protease cathepsins play a pivotal role in extracellular matrix (ECM) remodeling and have been implicated in the development and progression of atherosclerosis-based cardiovascular diseases. An imbalance in expression between cathepsins (such as cathepsins S, K, L, C) and their inhibitor cystatin C may favor proteolysis of ECM in the pathogenesis of cardiovascular disease such as atherosclerosis, aneurysm formation, restenosis, and neovascularization. New insights into cathepsin functions have been made possible by the generation of knock-out mice and by the application of specific inhibitors. Inflammatory cytokines regulate the expression and activities of cathepsins in cultured vascular cells and macrophages. In addition, evaluations of the possibility of cathepsins as a diagnostic tool revealed that the circulating levels of cathepsin S, K, and L, and their endogenous inhibitor cystatin C could be promising biomarkers in the diagnosis of coronary artery disease, aneurysm, adiposity, peripheral arterial disease, and coronary artery calcification. In this review, we summarize the available information regarding the mechanistic contributions of cathepsins to ASCVD.