Improving muscle health throughout the aging process

A human muscle map has revealed the processes behind age-related muscle deterioration, and the mechanisms to counteract them.

As humans age, their muscles progressively weaken. This can affect the ability to perform everyday activities like standing up and walking. For some people, muscle loss worsens, leading to falls, immobility, a loss of autonomy and a condition called sarcopenia. However, the reasons why muscles weaken over time have remained poorly understood.

The human muscle map, published in Nature Aging, uncovers new cell populations that may explain why some muscle fibres age faster than others. It also identifies compensatory mechanisms the muscles employ to combat aging.

The findings offer avenues for future therapies and interventions to improve muscle health and quality of life as people age.

What did the study involve?

Researchers from the Wellcome Sanger Institute and their collaborators at Sun Yat-sen University, China applied single-cell technologies and advanced imaging to analyse human skeletal muscle samples from 17 individuals aged 20 to 75. By comparing the results, they shed new light on the many complex processes underlying age-related muscle changes.

This study was part of the international Human Cell Atlas initiative to map every cell type in the human body, to transform understanding of health and disease.

The team discovered that genes controlling ribosomes, responsible for producing proteins, were less active in muscle stem cells from aged samples. This impairs the cells’ ability to repair and regenerate muscle fibres as people age. Further, non-muscle cell populations within these skeletal muscle samples produced more of a pro-inflammatory molecule called CCL2, attracting immune cells to the muscle and exacerbating age-related muscle deterioration.

Age-related loss of a specific fast-twitch muscle fibre subtype, key for explosive muscle performance, was also observed. However, the researchers discovered for the first time several compensatory mechanisms from the muscles appearing to make up for the loss. These included a shift in slow-twitch muscle fibres to express genes characteristic of the lost fast-twitch subtype, and increased regeneration of remaining fast-twitch fibre subtypes.

The team also identified specialised nuclei populations within the muscle fibres that help rebuild the connections between nerves and muscles that decline with age. Knockout experiments in lab-grown human muscle cells by the team confirmed the importance of these nuclei in maintaining muscle function.

“Through the Human Cell Atlas, we are learning about the body in unprecedented detail, from the earliest stages of human development through to old age. With these new insights into healthy skeletal muscle aging, researchers all over the world can now explore ways to combat inflammation, boost muscle regeneration, preserve nerve connectivity and more. Discoveries from research like this have huge potential for developing therapeutic strategies that promote healthier aging for future generations,” said Dr Sarah Teichmann, senior author of the study from the Wellcome Sanger Institute, and co-founder of the Human Cell Atlas.

Image credit: iStock.com/Fabio Camandona