Researchers at this institution have published findings on the Human Skeletal Muscle Aging Atlas, focusing on the impact of aging on stem cells within muscle tissue. They discovered significant alterations in gene expression associated with inflammation and reduced activity, which are common characteristics of aging. The presence of chronic inflammation, caused by senescent cells and immune responses to molecular damage, plays a key role in age-related dysfunctions. One notable dysfunction is the decline in stem cell activity, leading to a decreased supply of daughter somatic cells for tissue repair and regeneration.
A comprehensive analysis of 90,902 single cells and 92,259 single nuclei from 17 donors enabled the researchers to map the aging process in adult human intercostal muscle. They identified cellular changes in different muscle compartments, revealing concurrent aging mechanisms affecting multiple cell types. In the muscle stem cell compartment, they observed a decrease in MuSC activation due to downregulation of ribosome assembly, along with heightened pro-inflammatory pathways and cytokine expression. The muscle fiber microenvironment also exhibited increased expression of pro-inflammatory chemokines, potentially attracting immune cells and contributing to the inflammatory environment in aged muscle.
The integrated aging atlas highlighted a general decline in gene expression, increased inflammation, and reduced pathways related to growth, repair, and innervation. Interestingly, the upregulation of CCL2 in the aging microenvironment was unique to humans and not observed in mice, suggesting a species-specific regulation of inflammation. Additionally, the atlas showed an increase in nuclei associated with the neuromuscular junction, indicating potential re-innervation, and described the regeneration and upregulation of fast-type markers in slow-twitch myofibers to compensate for the loss of fast-twitch fibers with age. The role of the aging muscle microenvironment in attracting immune cells was also documented.
The findings shed light on age-related changes in muscle stem cell biochemistry and provide valuable insights into the mechanisms underlying age-related frailty and sarcopenia. The research opens new avenues for understanding and potentially mitigating the effects of muscle aging on overall health. More details can be found in the published article at the link provided.
Link: https://doi.org/10.1038/s43587-024-00613-3
