International Business Department           Liu Bojia           April 22, 2023

  As we get older, many people will lament that their hair is becoming less and less able to grow. In fact, in addition to hair, there is one other thing that is gradually decreasing in our body, and that is muscle. And more than hair, muscle loss has a more prominent impact on health.

  Skeletal muscle is not only vital for athleticism, but also plays a key role in metabolism and immune regulation, and increased muscle mass can also improve brain health. However, as we age, muscle size and mass decrease, as does muscle strength. In people over the age of 65, muscle mass declines at a rate of 6 to 15 per cent per year. As a result of this loss of skeletal muscle, some older people suffer from sarcopenia, which is a debilitating condition that makes them vulnerable to falls and fractures and increases their risk of death.

  Therefore, preventing or slowing down the ageing of skeletal muscles is a very important aspect to achieve the goal of healthy ageing and improve the quality of life in old age.

  Recently, a new study jointly led by researchers from the Wellcome Sanger Institute and Sun Yat-sen University has constructed the first comprehensive map of human skeletal muscle aging, from which a comprehensive picture of the complex changes that occur in muscle with age is revealed. The new findings explain why certain muscle fibres are more susceptible to ageing, and also identify compensatory mechanisms by which muscles cope with ageing, providing insight into how to reduce muscle loss and promote muscle regeneration.

  The paper notes that while most previous studies on muscle ageing have focused on one specific mechanism or cell type, this comprehensive map aims to provide a holistic understanding of muscle age ing.

  To this end, the team collected intercostal muscle samples provided by 17 adults, including eight young adults aged 20-40 years and nine older adults aged 60-75 years, and applied cutting-edge single-cell and imaging techniques to analyse the muscle's cellular composition, including different types of myofibroblasts, muscle stem cells, as well as other non-muscle cells, such as immune cells and fibroblasts, in the muscle microenvironment. Considering that skeletal muscle myofibers are composed of a single cell but include multiple nuclei, the researchers also combined single-cell sequencing and nuclear transcriptome data to carry out the analysis.

  Muscle fibres are classified according to their contraction speed, protein composition and metabolic profile into "fast fibres", which are capable of explosive movements, and "slow fibres", which are more involved in endurance activities. The results of the study showed that certain types of fast-moving muscle fibres show a particularly marked decline with age ing. However, the study also revealed, for the first time, that there are several compensatory mechanisms in the muscle itself, such as the fact that some slow fibres begin to express genes specific to fast fibres, and that the remaining fast fibres regenerate at an accelerated rate. All of these compensatory mechanisms help to reduce the lack of fast muscle fibres.

  Senescence of muscle stem cells is also one of the researchers' focuses, as such cells are key to repairing muscle damage and generating new muscle. The results showed that the genes controlling ribosomes were less active in the muscle stem cells of the older samples, and it was this type of change that made the cells less able to repair and regenerate muscle fibres with age.

  In addition, the population of non-muscle cells in the muscle microenvironment produces more pro-inflammatory factors such as CCL2 and CCL3 with aging, attracting more immune cells to the muscle and exacerbating muscle decline during aging.

  Along with aging, the number of neuromuscular junctions (i.e., "neuromuscular junctions"), where nerves control muscles, also decreases. However, mapping has shown that specialised groups of nuclei in muscle fibres help to re-establish the neuromuscular junction. Further experiments confirmed the essential importance of these nuclei in maintaining muscle function.

  Professor Hongbo Zhang of Sun Yat-sen University, a co-corresponding author of the study, noted that despite the fact that muscles are affected by aging, the new study provides a wealth of detail revealing how to keep them functioning for as long as possible.

  The study is part of the Human Cell Atlas project, and Dr Sarah Teichmann, the leader of the project and a co-corresponding author of the paper, commented, "These new insights into healthy skeletal muscle aging will help researchers around the world to explore new ways to fight inflammation, promote muscle regeneration, maintain neural connections, and more.