How muscles age

Sarcopenia – age–related loss of skeletal muscle mass and function - leads to limited mobility and an increased risk of falls. And although scientists know how muscle tissue changes with age, the underlying molecular mechanisms of sarcopenia remain poorly understood. Modern methods of treating sarcopenia mainly include recommendations of moderate physical activity or proper nutrition, and they have shown modest effectiveness.

Some pharmaceutical drugs are currently being tested in clinical trials, some of the candidate drugs act on mechanisms in which a protein called Klotho is involved. Preliminary data indicate that with age, its number gradually decreases. Researchers from the University of Pittsburgh have tested whether restoring Klotho levels can delay the development of sarcopenia.

First, a group led by Zachary Clemens characterized and compared changes in the structure, function and activity of genes in skeletal muscles at different stages of life. They divided the mice into four age categories: young, middle-aged, elderly and old. In each age group, the researchers assessed muscle mass, type of muscle fibers, accumulation of adipose tissue in the muscles and skeletal muscle function. Mild sarcopenia was noted in elderly mice, which was gaining momentum by old age and manifested all clinical signs.

The researchers studied changes in gene activity in the myocytes of mice of all four categories and found progressive changes in genes associated with signs of aging.

Using an integrative approach and analyzing gene expression levels and protein-protein interactions, the group created a complex scheme, and then studied how this network of interactions changes over time.

Using this scheme, the researchers assessed the appearance of deviations in molecular interactions in myocytes over time. They found the greatest difference between young and old age groups and a small difference between elderly and old mice. In addition, when the authors evaluated the data on the work of muscle genes of people from different age groups, they found that the deviation from the norm was minimal in the fourth decade of life, after which the "entropy" increased. This interested researchers, because sarcopenia often begins to develop in the fourth decade of life.

To find out whether the Klotho protein has a regenerative effect on muscles, the researchers used an adenovirus vector to inject additional copies of its gene into mice after injuries. The processes of muscle replacement by connective tissue in these animals slowed down, and the number of structures associated with energy production in myocytes increased. Injured mice injected with the Klotho gene also showed an improvement in muscle function and a doubling of the endurance of the whole body.

Finally, the team investigated whether Klotho could reverse sarcopenia in mice and found that an increase in its expression led to some improvements in a group of older mice: energy production increased by 17%, and endurance when holding the weight of the whole body was 60% more compared to mice without treatment. But this has only been seen in older mice, not in the oldest animals.

Further studies have shown that Klotho affects genes associated with signs of aging in all age groups, but older mice have a disrupted gene response.

In future studies, the authors will try to find out whether increasing Klotho levels at a younger age can prevent sarcopenia in old age and even senile age.

Article by Z.Clemens et al. The biphasic and age-dependent impact of Klotho on hallmarks of aging and skeletal muscle function is published in the journal eLife.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of eLife Sciences: Study reveals roadmap of muscle decline with age.