Absence of a Single Protein Spurs Muscle Aging in Mice

Proposed mechanism of skeletal muscle mitochondria involvement in sarcopenia

Muscle wastage and loss of strength, ie sarcopenia causes loss of quality of life. 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. This protein could serve as a therapeutic target to ameliorate sarcopenia in the elderly.

They demonstrate that low activity of this protein in 24-month old mice (equivalent of a person aged 80) is directly associated with muscle wastage and 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 thus muscle conditions of aged mice.

“Over 5 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,” explains the first author of the article David Sebastián, an IRB Barcelona and CIBERDEM researcher. The United Nations estimates that in 2050 there will be 2.1 billion people over 60, a figure that accounts for 22% of the world population. Currently, this figure stands at 12%.

Dr. Zorzano’s lab is running a study in collaboration with physicians working in geriatric medicine at Sant Joan de Déu Hospital to demonstrate that Mitofusin 2 is also repressed in human aging. “We need to demonstrate this if we want to translate our findings to clinical practice,” he says. In addition, this group also has the technology ready to search for pharmacological agents capable of boosting Mitofusin 2 activity.

Another phenomenon of extreme muscle degeneration is cachexia, associated with disease, especially cancer. “If we can find a molecule that improves muscle status, it should be tested against cachexia in cancer patients,” states Zorzano, “because in some cases this is the real cause of death in this patient group.”

Mitofusin 2 is a mitochondrial protein involved in ensuring the correct function of mitochondria, and it has several activities related to autophagy, which removes damaged mitochondria. The loss of Mitofusin 2 impedes correct function of mitochondrial recycling and consequently damaged mitochondria accumulate in muscle cells.

Thanks to this study, 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. This could serve as an alternative metabolic mechanism used by Mitofusin to increase skeletal muscle autophagy and to maintain a healthier mitochondrial system. http://www.irbbarcelona.org/en/news/the-absence-of-a-single-protein-spurs-muscle-aging-in-mice  http://onlinelibrary.wiley.com/doi/10.1113/JP271212/full