With age, the elderly are prone to falls, and the consequences are often severe. This is due to the gradual degeneration of muscles as part of the aging process. A recent study from an international cooperative team published their findings in the authoritative journal Nature—a comprehensive multimodal single-cell atlas of skeletal muscles covering different genders and age groups. This atlas is currently the most comprehensive single-cell reference for the process of muscle aging, expected to provide strong scientific support for developing prevention and treatment strategies for muscle aging.
In this study, the research team analyzed nearly 387,000 cells in the lower limb muscle samples of individuals ranging from 15 to 99 years of age, delving into the evolution of cell types during the aging process. The study revealed that key muscle cells begin to slowly disappear with age, especially those supporting rapid and powerful activities, adversely affecting the motor abilities of the elderly and increasing the likelihood of falls.
Muscles consist of slow-twitch fibers and fast-twitch fibers, which are responsible for endurance activities and explosive movements, respectively. It is noteworthy that the study found that with aging, slow-twitch fibers remain relatively stable, while fast-twitch fibers gradually diminish. The research team also established the molecular pathways for the degeneration of these two types of fibers, revealing the difference in mechanisms against aging between fast and slow-twitch fibers, with slow-twitch fibers displaying a stronger resistance to aging.
Furthermore, with increasing age, the research team also observed the emergence of new groups of muscle fibers in muscle samples, which are difficult to find in the muscles of young people but become increasingly apparent in the elderly, such as regenerative and degenerative subtypes of muscle fibers. Degenerative fibers may be the first cells to age, while regenerative fibers play a special protective role in older individuals, helping muscles maintain function and slow down the aging process.
Scientists’ in-depth study of the mechanism of muscle cell aging has previously relied on time-consuming and inefficient muscle tissue sectioning, which often resulted in data inaccuracies. However, with single-cell sequencing technology, researchers can now perform more precise and rich analyses of cell populations, unraveling the biological mysteries behind aging.
Single-cell sequencing technology plays an increasingly critical role in the development of modern biotechnology, with applications spanning the resolution of cell heterogeneity, the revelation of relationships between cell populations in microenvironments, and tracking the progression of diseases. This technology has driven the scientific research paradigm shift from traditional hypothesis-driven models to data-driven exploration of unknown domains, opening new possibilities for scientific advancement.
The opportunity for in-depth research originated in 2019 when, based on advanced technologies such as single-cell sequencing developed independently by BGI, Miguel A. Esteban’s research team achieved significant results in the field of stem cell research. Since then, the team decided to expand the scope of single-cell genomics research to the fields of aging and regeneration, with a particular focus on muscle aging-related studies.
During the research, the collaborative team discovered a key phenomenon: a type of quiescent cell in muscle stem cells, endowed with superior repair capacity. However, with aging, the number of these stem cells gradually decreases and they remain in an activated state, resulting in their inability to proliferate and differentiate effectively to repair damaged muscles. This mechanism could be one of the reasons for the exhaustion of muscle stem cells during aging.
Furthermore, the study points out that during the aging process, endothelial cells undergo significant changes, with increased signals for inflammation and the attraction of immune cells. The number of immune cells increases and activates the inflammatory response. These changes lead to muscles that are more difficult to repair after damage in old age and may drive systemic inflammation, accelerating the decline in overall bodily functions in the elderly.
An important finding of the study is that it provides a new quantitative diagnostic approach for age-related muscle atrophy, namely amyotrophic lateral sclerosis (ALS). Patients with age-related muscle atrophy or ALS are often difficult to diagnose accurately. By correlating cellular or molecular characteristics in the patients’ muscle samples with a newly established single-cell atlas of muscle aging, the study provides quantitative criteria for diagnosis. The cellular subtypes revealed in the aging process by this research also offer the possibility of targeted treatment and reversal of muscle aging, providing a reference for the treatment of ALS.
The study demonstrates the immense value of international collaboration in solving complex scientific problems and reflects the importance of multidisciplinary team cooperation. With the arrival of a society with longer life expectancy, the issue of chronic diseases in the elderly is becoming increasingly prominent. Pura Muñoz-Cánoves, co-corresponding author and chief researcher at the Altos Labs in San Diego, indicates that this research aims to deepen the understanding of muscle function and aging by establishing a comprehensive multimodal single-cell atlas of skeletal muscle, in order to meet the challenges brought about by an aging society.
