Researchers have gained new insight into the mechanisms involved in how skeletal muscles lose their mass and strength as people age, called sarcopenia.

Sarcopenia is common in older people and is an important contributor to frailty. It affects balance, the way a person moves and their overall ability to perform daily tasks. With an aging population, sarcopenia is a serious global public health problem.

In the first ever study to compare muscle tissue from groups of older people with sarcopenia across different geographies, researchers identified changes in the cells and molecules within muscle, which may explain why some people develop sarcopenia and some people do not.

The  published in Nature Communications found that the muscle from individuals with sarcopenia had reduced activity of the key energy-producing pathway and a decrease in activity of the components that make up all five complexes in the energy production pathway critical to maintaining muscle strength and function.

Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity,

These changes were found in the cohort of men from the Singapore cohort of the study and replicated in cohorts from the UK (Hertfordshire Cohort Study) and Jamaica.

Moreover, results showed that sarcopenia was also associated with reduced levels of enzymes involved in the recycling of NAD+, which acts as a metabolic sensor in the cell and regulates energy production pathways.

The team now plans to explore why the changes in the energy-producing pathway occur and are looking at genetic and nutritional factors.

One of the lead authors, said: "Most studies to date have compared muscle tissue from young people to older people but we wanted to understand why there is variability in the loss of muscle mass and strength between elderly individuals."

"This is a really novel study, using advanced sequencing techniques for the first time, which has allowed us to identify the molecular basis of why some people develop sarcopenia and others do not in old age."

A co-author added: "Sarcopenia is becoming a major health care challenge for all countries, so much so that it was recently recognised as a medical condition. By identifying these differences in activity in key pathways within muscle cells we can now start to develop therapeutic interventions that will hopefully help a lot of people to remain active and healthy in later life."

https://www.southampton.ac.uk/news/2019/12/muscle-bones.page

https://www.nature.com/articles/s41467-019-13694-1

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fmitochondrial-oxidative&filter=22