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.
There is plenty of work, and yet people with a disability are still often sidelined. One plus one is two, or so you’d think: this is the perfect time to help this group of workers find a job. The intention is there, also within the University, but...
The Dutch science funding agency NWO recently awarded a large research project into new concepts for energy-efficient information technology of no less than ten million euros
On the recommendation of the Board of the University of Groningen, Dr Frans J. Sijtsma has been appointed as academic director of the Rudolf Agricola School for Sustainable Development with effect from 1 February 2023. This concerns a 0.5 FTE...
The UG website uses functional and anonymous analytics cookies. Please answer the question of whether or not you want to accept other cookies (such as tracking cookies).
If no choice is made, only basic cookies will be stored. More information