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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.
The problem:
Brain health inevitably declines in old age, with both a decrease in the volume of certain brain regions and a decline in cognitive function. The dysfunction of the mitochondria, the power plants of the cell, appear to play a significant role in this decline. In old age, mitochondria become less efficient at producing ATP, the cell’s universal fuel source, and also produce an increasing quantity of harmful byproducts known as reactive oxygen species. The brain, being the most energy-hungry organ in the body, is vulnerable to both of these changes.
Studying how mitochondria relate to brain ageing in humans is challenging because it is difficult to measure mitochondrial function in the brain. In this study, researchers wanted to see if the mitochondria in muscle tissue could be used as a proxy for brain mitochondrial health, and made some interesting findings in the process.
The discovery:
In the study, researchers followed up 649 participants (mean age of 65.9) for between 1 and 11 years. 463 of these participants had repeated brain MRI scans during the followup period. At the start of the study, researchers had participants perform a knee-extension exercise within a magnetic resonance scanner. This allowed them to measure a proxy of muscle mitochondrial function called kPCr, which is the rate at which the muscle is able to replenish phosphocreatine after exercise, a process requiring ATP. They found that better kPCr was correlated with lower loss of volume in many brain regions, as well as improved markers of white matter health.
This relationship isn’t very surprising considering that physical exercise improves both muscle and brain health. However, even after controlling for confounding factors including physical fitness, the relationship remained (but was diminished), suggesting that muscle mitochondrial health itself is correlated with less loss of brain volume and improved white matter structure in old age.
The implications:
Better muscle mitochondrial health appears to be associated with slower brain ageing, which could be because mitochondrial health in muscle tissue is a proxy for mitochondrial health elsewhere. Mitochondrial dysfunction in one tissue may promote dysfunction in other tissues through the release of signals such as inflammatory molecules. It’s also possible that muscles with healthier mitochondria release signalling molecules that promote brain health. In other words, while physical activity undoubtedly benefits the brain directly, the muscles you are left with afterwards may continue to promote brain health in other ways.
Since this study was observational, it can’t prove that improved muscle mitochondrial function caused reduced brain ageing. Even though researchers controlled for things like fitness at the time of the study, participants with healthier mitochondria might have been more physically active in the past, which could have had lasting impacts on the brain. While the mechanisms will require more study, the real practical takeaway here is simply a reminder that maintaining healthy muscle is likely to slow brain ageing in multiple ways.
Higher skeletal muscle mitochondrial oxidative capacity is associated with preserved brain structure up to over a decade https://doi.org/10.1038/s41467-024-55009-z
Title image by Alina Grubnyak, Upslash
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