During the natural aging process, many functions of our skeletal muscles inevitably decline. However, an interesting recent study by Sun Yat-sen University revealed that skeletal muscles may also "self-rescue," potentially possessing resistance mechanisms during their aging phase to cope with functional decline.
Recently, Professor Zhang Hongbo's team from Sun Yat-sen University School of Medicine, in collaboration with partners, utilized single-cell single-nucleus transcriptomic sequencing technology to establish the most comprehensive cell type atlas to date, spanning all age groups of adults, depicting the aging process of skeletal muscles and analyzing various cellular types and multiple regulatory mechanisms involved in skeletal muscle aging. The findings were published in "Nature Aging."
"Nature Aging" published a brief article on this research, quoting Professor Vittorio Sartorelli from the National Institutes of Health in the United States, who highly praised the study: "A comprehensive blueprint of the evolution of all skeletal muscle cells from adulthood to aging in humans, providing a crucial foundation for future in-depth studies on human skeletal muscle physiology and aging mechanisms."
How do skeletal muscles resist aging? This is attributed to a special type of muscle fiber cell. Unlike most cells in the body, these cells have hundreds of "brains" - cell nuclei - controlling their behavior and characteristics. The latest research discovered a type of synaptic regulatory muscle fiber nucleus associated with promoting synapse formation, which spontaneously increases in aging skeletal muscles. The team speculates that as a protective cell nucleus, they may slow down skeletal muscle functional decline by reshaping neural innervation.
During the aging process of skeletal muscles, white muscle fibers in the human body often deteriorate earlier than red muscle fibers. However, the study found that both types of muscle fiber cells may exhibit "self-rescue" behavior. When the number of white muscle fibers decreases, the cell nuclei of structurally sound red muscle fibers begin to acquire characteristics of white muscle fibers, undergoing spontaneous compensatory repair. At this point, aging white muscle fibers also show signs of regeneration, collectively creating a resistance mechanism against skeletal muscle aging.
Given the prolonged aging process and complex cellular structure of skeletal muscles, Professor Zhang Hongbo's team collaborated with Professor Sarah Teichmann from the Sanger Institute in the UK to collect skeletal muscle samples over a broader time span and different locations. The samples ranged in age from 20 to 75 years, and the study introduced single-nucleus sequencing methods to investigate the distinctive features of each cell nucleus in skeletal muscle fibers.
Muscle atrophy and weakness accompanying aging are major causes of restricted mobility, falls, fractures, and paralysis in the elderly. Co-corresponding author Zhang Hongbo stated that the functional decline caused by skeletal muscle aging poses increasingly severe health risks with advancing age, ranging from muscle atrophy to severe loss of basic motor functions.
In late 2023, Professor Zhang Hongbo's team released the first single-cell spatiotemporal map of human limb development, deciphering the determining process of cell evolution and spatial positioning in fetal limbs. The two research projects on limb development and skeletal muscle aging were conducted almost simultaneously. "We focus on the two extremes of cell fate. If development addresses 'where we come from,' aging tackles 'where we are going,'" Zhang Hongbo explained.
The research team has provided an integrated map of skeletal muscle aging and a mouse skeletal muscle aging map in website format to study species-conserved aging mechanisms. Additionally, based on previous limb development work, a spatiotemporal cell map of embryonic limb development has been provided for joint exploration of skeletal muscle development, growth, and aging mechanisms.
"We hope these maps will provide comprehensive data references for researchers interested in the basics or clinical aspects of skeletal muscle development, aging, physiology, and pathology, and we look forward to more research contributing to the field of skeletal muscle by utilizing this information," Zhang Hongbo expressed.
For more information on the related paper: https://doi.org/10.1038/s43587-024-00613-3
