Mitochondria are the power plants of the cell, producing chemical energy store molecules used to power cell activities. Energy hungry tissues such as muscle and brain are particularly sensitive to differences in mitochondrial function. Here, researchers show in a human study population that better mitochondrial function in muscle tissue correlates with slower aging in many areas of the brain. Interestingly, this relationship occurs regardless of physical fitness, though it is true that any given individual can be expected to achieve better mitochondrial function through attaining a greater degree of physical fitness. Physical fitness is beneficial in many ways, but it is the improvement in mitochondrial function resulting from greater physical fitness that drives the relationship with brain aging noted here, not the fitness per se.
This longitudinal study demonstrates a significant relationship between skeletal muscle mitochondrial oxidative capacity and brain structural changes up to over a decade, emphasizing the strong connection between mitochondrial health and brain aging and neurodegeneration. By investigating two different neuroimaging modalities across multiple brain regions, we identified specific brain regions and connecting tracts that were related to mitochondrial oxidative capacity assessed in the skeletal muscle. These longitudinal findings provide mechanistic insights into the connection between muscle bioenergetics and brain aging and lay a foundation for future research on mitochondrial bioenergetics in the brain.
One potential mechanism is that muscle mitochondrial function indicates general mitochondrial health and that muscle mitochondria can be considered a proxy measure of mitochondrial health across multiple tissues, including the brain. Another possibility is that the measure of oxidative capacity captures general muscle health and that positive signaling through soluble molecules and/or microvesicles may act in neurotrophic signaling that promotes brain health. While skeletal muscle oxidative capacity is related to fitness, the longitudinal associations between skeletal muscle oxidative capacity and brain atrophy were independent of concurrent fitness levels. Longitudinal associations with microstructural change persisted after accounting for the fitness measure of 400-meter walk time but were attenuated after adjusting for VO2 max. This attenuation is not surprising as fitness and vascular factors are strongly associated with white matter microstructure.
Because of the observational nature of this study, the detected longitudinal associations may shed light on but do not prove a causal relationship. In addition, we cannot exclude that higher skeletal muscle oxidative capacity reflects in part the lifetime history of exercise and physical activity which may affect several aspects of brain health but may not be fully captured by the assessment of current fitness levels.
