Sarcopenia is the name given to progressive age-related loss of muscle mass and strength. Here one possible contributing cause of the condition is explored: reduced levels of a protein involved in the quality control of mitochondria, which may allow damaged mitochondria to accumulate more readily in muscle tissue. Researchers have been lobbying for a decade to have sarcopenia formally defined as a medical condition, but that hasn't yet come to pass. The causes of sarcopenia are still debated; there are many possible contributions with plausible supporting evidence, but it isn't at all clear as to how they interact or which are the most important. Researchers have suggested fat tissue infiltration into muscles, the lack of exercise prevalent in older populations, rising levels of inflammation, failing leucine metabolism, vascular aging in muscles, Wnt signaling changes, and declining activity in muscle stem cells, among others. Interventions that slow aging, such as calorie restriction, also tend to slow the progression of sarcopenia, but beyond that and exercise there isn't yet much that can be done about this condition.
At about 55 years old, people begin to lose muscle mass, this loss continues into old age, at which point it becomes critical. The underlying causes of sarcopenia are unknown and thus no treatment is available for this condition. A study has discovered that Mitofusin 2 is required to preserve healthy muscles in mice. These researchers indicate that this protein could serve as a therapeutic target to ameliorate sarcopenia in the elderly, observing that during aging mice specifically lose the expression of Mitofusin 2 in muscle. They demonstrate that low activity of this protein in 24-month old mice (the equivalent of a person aged 80) is directly associated with muscle wastage and the sarcopenia observed. The scientists confirm the link between the loss of Mitofusin 2 and muscle aging when the expression of the protein is suppressed in the muscles of 6-month-old animals (equivalent to a person of 30) as these animals showed accelerated aging, reproducing the muscle conditions of aged mice.
"Over five years we have collected sufficiently significant evidence that demonstrates the contribution of Mitofusin 2 to the maintenance of good muscle health in mice and that allows us to consider a therapeutic strategy for sarcopenia. Sarcopenia is not a minor issue because it impedes some elderly people from going about their everyday lives. If we want to boost the health of the elderly then this problem has to be addressed." The researchers are running a study in collaboration with physicians working in geriatric medicine to demonstrate that Mitofusin 2 is also repressed in human aging. In addition, this group also has the technology ready to search for pharmacological agents capable of boosting Mitofusin 2 activity.
Mitofusin 2 is a mitochondrial protein involved in ensuring the correct function of mitochondria, and it has several activities related to autophagy, a crucial process for the removal of damaged mitochondria. The loss of Mitofusin 2 impedes the correct function of mitochondrial recycling and consequently damaged mitochondria accumulate in muscle cells. The researchers have also identified and described an autophagy rescue system which kicks in regardless of Mitofusin 2 levels and allows cells to partially recover the mitochondrial recycling system in skeletal muscle. The scientists suggest that this could serve as an alternative metabolic mechanism used by Mitofusin to increase skeletal muscle autophagy and to maintain a healthier mitochondrial system.