A new target for the treatment of muscle degeneration
Scientists at the Institute of Biomedical Research in Barcelona and the University of Barcelona, working under the guidance of Professor Antonio Zorzano, have found that the absence of mitofuzin-2 protein in the muscles of young mice accelerates the aging process and causes early development of sarcopenia. As a result, the muscles of animals in terms of parameters approach the muscles of old mice.
By about the age of 55, many people develop sarcopenia – atrophy of muscle tissue, accompanied by a decrease in muscle strength and is one of the manifestations of aging that worsens the overall condition of the body. As we age, this condition worsens and can significantly worsen the quality of life. To date, the causes of its development are unclear and there are no treatment methods.
In experiments on mice, the authors found that as mice age, the expression of mitofuzin-2 selectively decreases in muscle tissue. They demonstrated that the low activity of this protein in the muscles of 24-month-old mice (the equivalent for humans is 80 years old) is directly associated with atrophy of muscle tissue and the development of sarcopenia. The relationship between the loss of mitofuzin-2 and the aging of muscle tissue was confirmed by the fact that the suppression of the activity of this protein in the muscles of 6-month–old animals (equivalent for human age - 30 years) accelerated the aging process of animal muscles.
Mitofuzin-2 is a mitochondrial protein involved in maintaining the normal functioning of mitochondria. It has several functions associated with autophagy, a process critical for the removal of damaged mitochondria. The loss of this protein disrupts the processing function of mitochondria that have lost their working capacity, which leads to the accumulation of non-functional organelles in muscle cells.
The relationship between mitofusin-2 expression levels and muscle aging.
The authors suggest that stimulating the activity of mitofuzin-2 is a potential strategy for relieving the symptoms of sarcopenia. Also, this approach can theoretically be used to combat another phenomenon of muscle tissue atrophy, known as cachexia (extreme exhaustion of the body). This condition is associated with a number of diseases, especially malignant tumors, and is often the true cause of death of patients.
In addition, within the framework of the study, scientists identified and described an adaptive signaling mechanism triggered by age-related loss of mitofuzin-2, dependent on reactive oxygen species, mediated by the induction of transcription factor HIF1a (hypoxia-induced factor-1-alpha) and the BNIP3 protein. This mechanism partially compensates for the loss of mitochondrial autophagy and reduces the severity of mitochondrial damage.
The article by David Sebastián et al. Mfn2 deficiency links age-related sarcopenia and imposed autophagy to activation of an adaptive mitophagy pathway is published in The EMBO Journal.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Institute for Research in Biomedicine (IRB Barcelona): The absence of a single protein spurs muscle aging in mice.
23.06.2016