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- W4280496442 abstract "Abstract Introduction Chronological ageing is associated with mitochondrial dysfunction and increased reactive oxygen species (ROS) production in skeletal muscle. However, the effects of replicative ageing on skeletal muscle cellular metabolism are not well known. Using an established myoblast model of cellular (replicative) ageing, we investigated the impact of ageing on energy metabolism in murine C 2 C 12 myotubes. Methods Control (P7-11) and replicatively ‘aged’ (P48-51) C 2 C 12 myoblasts were differentiated over 72-120 h. Mitochondrial bioenergetics were investigated by respirometry and mitochondrial superoxide and cellular ROS were measured in the absence and presence of antimycin A (AA). Genes related to mitochondrial remodelling and the antioxidant response were quantified by RT-qPCR. Intracellular metabolites were quantified using an untargeted 1 H-NMR metabolomics pipeline. Results Mitochondrial coupling efficiency (Control: 79.5 vs. Aged: 70.3%, P =0.006) and relative oxidative ATP synthesis (Control: 48.6 vs. Aged: 31.7%, P =0.022) were higher in control vs. aged myotubes, but rates of mitochondrial superoxide production were lower (Control: 2.4×10 −5 ± 0.4 × 10 −5 vs. Aged: 9.7×10 −5 ± 1.6×10 −5 RFU/sec/cell; P =0.035). Replicatively aged myotubes had greater mRNA expression of mfn2 and Tfam compared to control. Yet, Nrf2 and PGC-1α expression were 2.8-fold and 3.0-fold higher in control versus aged myotubes over 24 h and 48 h ( P <0.05), respectively. Branched chain amino acids L-leucine, L-isoleucine and L-valine, and L-carnitine were less abundant in aged versus control myotubes. Conclusion(s) Replicative ageing is associated with bioenergetic uncoupling, increased ROS production and impaired amino acid metabolism. Our findings suggest that cellular mitochondrial dysfunction and altered energy metabolism may exacerbate the age-related decline in skeletal muscle mass and function." @default.
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- W4280496442 date "2022-04-21" @default.
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- W4280496442 title "Replicative ageing perturbs the metabolic signature of murine C<sub>2</sub>C<sub>12</sub> skeletal myotubes" @default.
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- W4280496442 doi "https://doi.org/10.1101/2022.04.20.488970" @default.
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