A groundbreaking study conducted by researchers from the Wellcome Sanger Institute and Sun Yat-sen University, China has unveiled the intricate processes underlying the aging of human muscles. By creating the first detailed cell atlas of aging human muscle, the study sheds light on the genetic and cellular activities involved in muscle degeneration and offers new directions for therapeutic interventions.

The study, published in the journal Nature Aging, utilized single-cell technologies and advanced imaging to analyze skeletal muscle samples from 17 individuals across the adult lifespan. By comparing the results, researchers uncovered new cell populations and identified compensatory mechanisms that explain why certain muscle fibers age faster than others.

One of the significant findings of the study was that genes controlling ribosomes, responsible for protein production, were less active in muscle stem cells from aged samples. This impairment hinders the cells' ability to repair and regenerate muscle fibers as we age. Additionally, non-muscle cell populations within the samples produced higher levels of a pro-inflammatory molecule called CCL2, which attracts immune cells to the muscle and worsens age-related muscle deterioration.

The study also highlighted the loss of a specific fast-twitch muscle fiber subtype associated with explosive muscle performance. However, researchers discovered several compensatory mechanisms within the muscles that appear to make up for this loss. These mechanisms include a shift in slow-twitch muscle fibers to express genes characteristic of the lost fast-twitch subtype and increased regeneration of the remaining fast-twitch fiber subtypes.

Furthermore, the researchers identified specialized nuclei populations within the muscle fibers that aid in rebuilding the connections between nerves and muscles, which decline with age. Experiments using lab-grown human muscle cells confirmed the importance of these nuclei in maintaining muscle function.

Veronika Kedlian, the first author of the study, expressed excitement about the multifaceted approach used in studying muscle aging, which combined different types of sequencing, imaging, and investigation. The researchers believe that these previously unknown cellular mechanisms of aging open up new areas for further research.

Professor Hongbo Zhang, the senior author of the study, emphasized the importance of understanding the aging process, particularly due to aging populations worldwide. The study's detailed insights into how muscles strive to maintain function despite the effects of aging provide valuable knowledge for promoting healthier aging.

Dr. Sarah Teichmann, senior author of the study and co-founder of the Human Cell Atlas, underscored the significance of this research for the development of therapeutic strategies that combat inflammation, boost muscle regeneration, and preserve nerve connectivity. The discoveries made in this study present immense potential for enhancing the quality of life during the aging process.

This study, part of the international Human Cell Atlas initiative, marks a significant milestone in mapping every cell type in the human body to transform our understanding of health and disease. With the comprehensive atlas of aging muscles, researchers worldwide can now explore various approaches to improve muscle health and develop interventions for healthier aging in future generations.

Reference: Kedlian, V.R., et al. "Human skeletal muscle aging atlas." Nature Aging, 15 April 2024.