This is the atlas of human skeletal muscle aging

In a world with rapidly aging societies, it is necessary to know the cause and progression of diseases in detail. Diseases that come with age. Skeletal muscle is the most important motor system in the human body and plays a fundamental role in the body’s metabolic regulation.

Researchers from Pompeu Fabra University, together with teams from China, the USA and Spain, analyzed the gene expression and epigenetics of the cells of this muscle type at different ages to produce the human atlas of its most complete aging process to date.

In a world with rapidly aging societies, it is necessary to know in detail the cause and progression of age-related diseases.

This study provides scientists with a resource for identifying skeletal muscle cells that may be suitable for medical, pharmacological and lifestyle interventions. This could impact physical health and help prolong life.

With increasing ageespecially for people over 80 years of age, Skeletal muscles suffer from sarcopenia, a progressive loss of muscle mass and function. This condition not only increases the individual’s disability, but also contributes to the rapid decline in general functions of the elderly.

To date, the biological basis of sarcopenia has not been systematically investigated at the single-cell scale. The teams They analyzed 387,000 individual cells in muscle biopsies from the lower extremities of 31 people of different gender, age and regional origin.

“As the most comprehensive atlas of human muscle aging to date at the single-cell level, this study will be a reference in the areas of aging as well as sarcopenia and frailty,” he says. Pura Muñoz-CánovesLabor Director.

Elements for predicting sarcopenia

Human skeletal muscles consist largely of muscle fibers (myofibers), of which there are two types. Type 1 muscle fibers are primarily involved in endurance physical activities such as long-distance running or cycling. They are characterized by slow muscle contraction speed, high aerobic metabolism and high mitochondrial activity.

The teams analyzed 387,000 individual cells in muscle biopsies from the lower extremities of 31 people.

Type 2 muscle fibers are important for physical activities that require sudden bursts of strength, such as jumping, sprinting, and weight lifting. They have a faster muscle contraction rate, are more prone to fatigue, and rely primarily on anaerobic metabolism for energy.

This work describes how skeletal muscle cell populations, including both individual nuclei in multinucleated fibers and traditional mononuclear cells, change with age, as well as the multicellular networks underlying these changes.

By comparing this data with genetic data, the researchers also identified key elements that predict susceptibility to sarcopenia. They found that type 2 muscle fibers steadily deteriorate as people age, while type 1 muscle fibers remain relatively stable and are better able to withstand the stresses of aging.

More prone to deterioration with age

During the aging process, cell metabolism is also impaired. While type 1 fibers become more glycolytic, type 1 muscle fibers increase oxidation. Importantly, new subtypes of proregenerative and prodegenerative myofibers emerge with increasing age. These new populations may contribute to triggering the degenerative cascade of aging muscles and are likely targets for interventions.

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Muscles can repair themselves. This occurs primarily through muscle stem cells, which, in the event of an injury, begin to proliferate and differentiate into muscles, fusing with each other or with existing muscle fibers to repair the damaged muscle.

As the most comprehensive atlas of human muscle aging to date at the single cell level, this study will serve as a reference for both the areas of aging and sarcopenia and frailty.

Pura Muñoz-Cánoves (UPF)

The researchers found that in aged muscles, these stem cells exit quiescence and enter a prematurely primed state, leading to a reduced ability to regenerate.

Meanwhile, endothelial cells also undergo changes with aging, with an increase in pro-inflammatory and chemotactic signals, while the number of immune cells increases and inflammatory programs are initiated.

These changes make muscles more susceptible to deterioration in response to injury and may promote systemic inflammation and accelerate the decline in overall physical function in the elderly.

New goals for treatment

In addition, by cross-comparison with genetic data, the researchers identified specific locations of each cell type in chromatin, the mix of DNA and proteins that make up chromosomes in human cells, that are associated with susceptibility to sarcopenia. These findings offer researchers potential new starting points for the future diagnosis and treatment of sarcopenia.

“Our research provides a new perspective for understanding human skeletal muscle aging and a scientific basis for the development of preventive and therapeutic strategies,” he explains. Miguel A. Estebanone of the two authors.

In the future, the team would like to create a more comprehensive atlas to provide optimism in addressing the challenges facing aging societies.

The authors believe it will be important to compare this atlas of human muscle aging with previous cell atlases from non-human primates and other species, as it will help make adaptive comparisons between species and predict disease susceptibility. In addition, it will also be an important reference for future studies on patients with neuromuscular diseases.

“We hope it will be the basis for much further research to slow or even prevent sarcopenia, frailty and muscle loss in older people by promoting healthier aging of the body over a longer period of time and increasing life expectancy,” says Muñoz-Cánoves.

In the future, the team aims to create a more comprehensive atlas to improve understanding of muscle function and aging and provide optimism in addressing the challenges facing aging societies.

Reference:

Lai, Y et al. Multimodal cell atlas of aging human skeletal muscle. Nature 2024

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