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Mitochondrial dysfunction in the ageing nervous and neuromuscular systems

Published on December 31, 2023   23 min

A selection of talks on Physiology & Anatomy

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0:00
Hi. My name is Amy Vincent. I'm a NUAcT fellow at Newcastle University. Today I'm going to be talking to you about mitochondrial dysfunction in the aging nervous and neuromuscular systems, with a particular focus on the neuromuscular system, which is my area of expertise.
0:20
To give a brief introduction to mitochondria to start off with, the mitochondria are organelles that are found in pretty much every cell in our body. They generate ATP by oxidative phosphorylation. Mitochondria are very different to other organelles in the fact that they have their own mitochondrial DNA, which encodes for several of the components for OXPHOS complexes and also for the tRNAs, and RNAs needed to synthesize these.
0:49
To talk a little bit about mitochondrial DNA, one of the very interesting things about mitochondrial DNA is that it is a small circular genome, and because it's present in hundreds of thousands of copies per cell, this means that when a mutation arises in a single copy, it might have a negligible impact on the function of mitochondria within that cell. However, over time, the mitochondrial DNA is replicated and degraded, and these mutations can accumulate, increasing the proportion of mitochondrial DNA that they are affecting and therefore, leading to mitochondrial dysfunction. This is a process that we call clonal expansion and something that I study quite heavily in skeletal muscle.
1:34
One of the reasons this is of interest to us is that, in patients with mitochondrial disease or in neuromuscular disorders and in aging, we see an accumulation of mitochondrial DNA mutations in skeletal muscle cells, and throughout life, these mutations increase in portion within cell. What we're looking at here is a section of skeletal muscle tissue that has been labeled for COX/SDH histochemistry. This is a reaction that leads to cells that have normal mitochondrial function being brown and cells that have dysfunctional mitochondria being blue. As mitochondrial DNA mutation accumulates within the skeletal muscle fibers, we will go from a situation where we have a brown cell to a blue cell. Understanding process by which this happens is an important mechanism to understand further disease and also for understanding how muscle ages and this is true in many other tissues as well.

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Mitochondrial dysfunction in the ageing nervous and neuromuscular systems

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