Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 model

Abstract

Background Young bone marrow transplantation (YBMT) has been shown to stimulate vascular regeneration in pathological conditions, including ageing. Here, we investigated the benefits and mechanisms of the preventive effects of YBMT on loss of muscle mass and function in a senescence‐associated mouse prone 10 (SAMP10) model, with a special focus on the role of growth differentiation factor 11 (GDF‐11). Methods Nine‐week‐old male SAMP10 mice were randomly assigned to a non‐YBMT group (n = 6) and a YBMT group (n = 7) that received the bone marrow of 8‐week‐old C57BL/6 mice. Results Compared to the non‐YBMT mice, the YBMT mice showed the following significant increases (all P < 0.05 in 6–7 mice): endurance capacity (>61.3%); grip strength (>37.9%), percentage of slow myosin heavy chain fibres (>14.9–15.9%). The YBMT also increased the amounts of proteins or mRNAs for insulin receptor substrate 1, p‐Akt, p‐extracellular signal‐regulated protein kinase1/2, p‐mammalian target of rapamycin, Bcl‐2, peroxisom proliferator‐activated receptor‐γ coactivator (PGC‐1α), plus cytochrome c oxidase IV and the numbers of proliferating cells (n = 5–7, P < 0.05) and CD34+/integrin‐α7+ muscle stem cells (n = 5–6, P < 0.05). The YMBT significantly decreased the levels of gp91phox, caspase‐9 proteins and apoptotic cells (n = 5–7, P < 0.05) in both muscles; these beneficial changes were diminished by the blocking of GDF‐11 (n = 5–6, P < 0.05). An administration of mouse recombinant GDF‐11 improved the YBMT‐mediated muscle benefits (n = 5–6, P < 0.05). Cell therapy with young bone marrow from green fluorescent protein (GFP) transgenic mice exhibited GFP+ myofibres in aged muscle tissues. Conclusions These findings suggest that YBMT can prevent muscle wasting and dysfunction by mitigating apoptosis and proliferation via a modulation of GDF‐11 signalling and mitochondrial dysfunction in SAMP10 mice.

Exercise Promotes Tissue Regeneration: Mechanisms Involved and Therapeutic Scope

“…Swimming training was shown to improve angiogenesis, increase the EPC number, and enhance EPC homing to the hindlimb ischemic sites in old mice [ 77 ]. Bone marrow transplantation can stimulate vascular regeneration and subsequently prevent muscle wasting in aged mice [ 78 ]. Interestingly, the neural protective effect of bone marrow mesenchymal stem cell transplantation could be enhanced by exercise training via the PI3K signaling pathway against spinal cord injury [ 79 ].…”

Application of mesenchymal stem cells for anti-senescence and clinical challenges

“…For mice, we can measure respiration and metabolism used by the metabolic cage and through the respiratory exchange ratio (RER) [ 60 ] to determine the degree of senescence or used by metabolic treadmill in research [ 61 ]. In addition, we can test strength and muscle of mice through small animal handgrip dynamometer [ 62 ] or a wire suspension test [ 63 , 64 ]. For the measurements of bone and fat, we can measure the volume of visceral and subcutaneous fat and analyze the the cortical bone and trabecular bone of the mice by bone imaging [ 61 ].…”