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Updated: Sep 16, 2025
Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans
Published on: February 16, 2017
An in vitro model to study molecular pathogenesis of sarcopenia established by a SASP-dependent human myotube culture
Kiyo-Aki Ishii1, Ryo Hashimoto1,2, Chikako Umeda1,2
1Department of Musculoskeletal Disease, National Center for Geriatrics and Gerontology (NCGG), Obu, Japan.
Abstract:
Sarcopenia is a condition that affects one's activities of daily livingand is rapidly increasing with the ages of the global population. However, the basic molecular mechanisms for prevention and treatment are not fully understood. Although rodent model animals have many valuable aspects for studying sarcopenia, some aspects and mechanisms differ from humans, such as immune response, metabolism, stress response, and myofiber composition. This study established a human cell-based in vitro model to elucidate the molecular mechanism by which SASP from senescence-induced human mesenchymal stem cells led to the narrowing of human myotube diameter, suggesting that this model is useful for studying sarcopenia. Gene expression profiling was performed the molecular mechanisms and devel on the model by RNA sequencing to identify genes whose expression was affected by SASP. Among these, the exposure to SASP upregulated PDK4 expression, and a PDK4 inhibitor, DCA, could increase myotube diameter and reverse SASP-mediated narrowing of the diameter. Pathway analyses suggested that SASP affected energy metabolism by activating OXPHOS and promoting the expression of mitochondrial function-related genes and mitochondrial biosynthesis factors. These results provide insights that contribute to developing new treatments for sarcopenia.
Insights
Cellular senescence secretes factors that cause muscle cells to shrink. A new human cell model identified PDK4 as a key factor, and inhibiting it reversed muscle cell narrowing, offering potential sarcopenia treatments.
Area of Science:
- Biomedical Science
- Cell Biology
- Gerontology
Background:
- Sarcopenia, age-related muscle loss, impacts daily living and lacks fully understood molecular mechanisms for prevention/treatment.
- Existing rodent models have limitations in mimicking human-specific responses like immune and metabolic differences.
Purpose of the Study:
- To establish a human cell-based in vitro model for studying sarcopenia.
- To elucidate the molecular mechanisms of how senescence-associated secretory phenotype (SASP) contributes to muscle atrophy.
Main Methods:
- Developed a human mesenchymal stem cell-induced senescence model.
- Utilized RNA sequencing for gene expression profiling to identify SASP-affected genes.
- Investigated the role of upregulated PDK4 and its inhibitor, DCA.
Main Results:
- SASP from senescent cells induced narrowing of human myotube diameter.
- PDK4 expression was upregulated by SASP; its inhibitor, DCA, reversed myotube narrowing.
- Pathway analysis indicated SASP impacts energy metabolism via OXPHOS and mitochondrial biosynthesis.
Conclusions:
- The human cell-based model is valuable for sarcopenia research.
- Targeting PDK4 presents a potential therapeutic strategy for sarcopenia.
- SASP-induced alterations in energy metabolism are implicated in sarcopenia development.
