Loss of mitochondrial respiratory flux is a hallmark of skeletal muscle aging, contributing to a progressive decline of muscle strength. Endurance exercise alleviates the decrease in respiratory flux, both in humans and in rodents.
Here, we dissect the underlying mechanism of mitochondrial flux decline by integrated analysis of the molecular network.
Mice were given a lifelong ad libitum low-fat or high-fat sucrose diet and were further divided into sedentary and running-wheel groups. At 6, 12, 18 and 24 months, muscle weight, triglyceride content and mitochondrial respiratory flux were analysed. Subsequently, transcriptome was measured by RNA-Seq and proteome by targeted LC-MS/MS analysis with 13C-labelled standards.
In the sedentary groups, mitochondrial respiratory flux declined with age. Voluntary running protected the mitochondrial respiratory flux until 18 months of age. Beyond this time point, all groups converged. Regulation Analysis of flux, proteome and transcriptome showed that the decline of flux was equally regulated at the proteomic and at the metabolic level, while regulation at the transcriptional level was marginal. Proteomic regulation was most prominent at the beginning and at the end of the pathway, namely at the pyruvate dehydrogenase complex and at the synthesis and transport of ATP. Further proteomic regulation was scattered across the entire pathway, revealing an effective multisite regulation.
Finally, reactions regulated at the protein level were highly overlapping between the four experimental groups, suggesting a common, post-transcriptional mechanism of muscle aging.
Two professors nominated by the University of Groningen have been awarded Royal Decorations on Tuesday 26 April. Professor K.U. Loos is appointed Knight of the Order of the Netherlands Lion. She received this honour from Mayor K. Schuiling at...
Cisca Wijmenga treedt per 1 september 2023 toe tot de Raad van Toezicht van de Hanzehogeschool.
The Board of the University of Groningen has taken note of the Letter to the House of Representatives regarding internationalization in higher education, sent to the House on Friday 21 April by the Minister of Education, Culture and Science Robbert...
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