Longevity Briefs: Could We Target Mitochondria To Prevent Muscle Ageing?

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:

Skeletal muscle plays a significant role in health and ageing. Muscle tissue is very metabolically active, even when not exercising. Consequently, it helps to prevent obesity and diabetes by acting as a sink to take up glucose (sugar) from the blood. In older age, stronger muscles also help to prevent falls and injuries, while weakened muscles can significantly impede everyday living.

Unfortunately, muscle mass and strength inevitably decline with age. The good news is that the extent of this decline can be greatly mitigated through exercise, even in the oldest age groups. However, we would also like to learn more about how muscles age so that we might develop treatments to maintain muscle health. In this study, researchers focus on the mitochondria within muscle tissue. Mitochondria are the power plants of the cell, using oxygen and nutrients in order to produce ATP, the molecule that powers muscle contraction as well as countless other vital processes throughout the body.

The discovery:

Researchers recruited 12 young and 10 middle aged participants with average (mean) ages of 27 and 55 years respectively. Researchers had participants undergo exercise tests and took muscle biopsies in order to study the characteristics of their mitochondria.

Unsurprisingly, the middle aged participants had lower maximum oxygen uptake and peak power output during exercise when compared with the younger participants, but this was not fully explained by pulmonary and cardiovascular differences. Electron microscopy showed that the intermyofibrillar mitochondria (the mitochondria located in-between the contractile filaments within the muscle cell) were equally dense between the two groups. However, the younger group had fewer, larger mitochondria while the middle aged participants tended to have more, smaller mitochondria, which the researchers termed mitochondrial fragmentation.

The subsarcolemmal mitochondria (located closer to the muscle’s blood supply) were less dense in middle aged participants. Overall, mitochondria from middle aged participants had a reduced density of cristae, which are the folded structures in which ATP production takes place. These changes were all well correlated with reductions in exercise capacity among the participants. The researchers estimated that 87% of the variance in maximal oxygen uptake could be explained by mitochondrial fragmentation and cristae density.

The implications:

This research suggests that changes in the structure and distribution of the mitochondria may be playing a significant role in muscle ageing and decline, at least in the first half of life. Mitochondria evolved from ancient bacteria and still share some bacterial characteristics, including the ability to divide or fuse together to form larger mitochondria or even larger, branching networks of connected mitochondria. In ageing muscle, it seems as though mitochondrial division wins out, resulting in impaired muscle function. Perhaps if we could reverse this trend, we could also rejuvenate ageing muscle tissue. This is unlikely to fix the whole problem, however, since other factors like the nervous system and hormonal changes are also known to contribute to muscle ageing.