Detrimental Effects of β2‐Microglobulin on Muscle Metabolism: Evidence From In Vitro, Animal and Human Research
ABSTRACT Background β2‐Microglobulin (B2M) has garnered considerable interest as a potential pro‐ageing factor, leading to speculation about its involvement in muscle metabolism and the development of sarcopenia, a key component of ageing phenotypes. To explore this hypothesis, we conducted a compre...
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Wiley
2025-04-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
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| Online Access: | https://doi.org/10.1002/jcsm.13745 |
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| author | Shibo Wei So Jeong Park Eunah Choi Il‐Young Jang Yan Zhang Yingqi Xue Yunju Jo Hee‐Won Jung Eunhye Ji Jin Young Lee Yujin Moon Eunju Lee Dongryeol Ryu Beom‐Jun Kim |
| author_facet | Shibo Wei So Jeong Park Eunah Choi Il‐Young Jang Yan Zhang Yingqi Xue Yunju Jo Hee‐Won Jung Eunhye Ji Jin Young Lee Yujin Moon Eunju Lee Dongryeol Ryu Beom‐Jun Kim |
| author_sort | Shibo Wei |
| collection | DOAJ |
| description | ABSTRACT Background β2‐Microglobulin (B2M) has garnered considerable interest as a potential pro‐ageing factor, leading to speculation about its involvement in muscle metabolism and the development of sarcopenia, a key component of ageing phenotypes. To explore this hypothesis, we conducted a comprehensive investigation into the impact of B2M on cellular and animal muscle biology, as well as its clinical implications concerning sarcopenia parameters in older individuals. Methods In vitro myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. For in vivo research, C57BL/6 mice aged 3 months were intraperitoneally given 250 μg of B2M daily, and muscular alterations were assessed one month later. Human blood samples were obtained from 158 participants who underwent assessments of muscle mass and function at an outpatient geriatric clinic affiliated with a teaching hospital. Sarcopenia and associated parameters were assessed using cut‐off values specifically tailored for the Asian population. The concentration of serum B2M was quantified through an enzyme‐linked immunosorbent assay. Results Recombinant B2M inhibited in vitro myogenesis by increasing intracellular reactive oxygen species (ROS) production. Furthermore, B2M significantly induced differential myotube atrophy via ROS‐mediated ITGB1 downregulation, leading to impaired activation of the FAK/AKT/ERK signalling cascade and enhanced nuclear translocation of FoxO transcription factors. Animal experiments showed that mice with systemic B2M treatment exhibited significantly smaller cross‐sectional area of tibialis anterior and soleus muscle, weaker grip strength, shorter grid hanging time, and decreased latency time to fall off the rotating rod, compared to untreated controls. In a clinical study, serum B2M levels were inversely associated with grip strength, usual gait speed and short physical performance battery (SPPB) total score after adjustment for age, sex, and body mass index, whereas sarcopenia phenotype score showed a positive association. Consistently, higher serum B2M levels were associated with higher risk for weak grip strength, slow gait speed, low SPPB total score, and poor physical performance. Conclusion These results provide experimental evidence that B2M exerted detrimental effects on muscle metabolism mainly by increasing oxidative stress. Furthermore, we made an effort to translate the results of in vitro and animal research into clinical implication and found that circulating B2M could be one of blood‐based biomarkers to assess poor muscle health in older adults. |
| format | Article |
| id | doaj-art-04b0b8efc2cc43e5aa286b66a1d85c8a |
| institution | DOAJ |
| issn | 2190-5991 2190-6009 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj-art-04b0b8efc2cc43e5aa286b66a1d85c8a2025-08-20T03:10:42ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-04-01162n/an/a10.1002/jcsm.13745Detrimental Effects of β2‐Microglobulin on Muscle Metabolism: Evidence From In Vitro, Animal and Human ResearchShibo Wei0So Jeong Park1Eunah Choi2Il‐Young Jang3Yan Zhang4Yingqi Xue5Yunju Jo6Hee‐Won Jung7Eunhye Ji8Jin Young Lee9Yujin Moon10Eunju Lee11Dongryeol Ryu12Beom‐Jun Kim13Department of Biomedical Science and Engineering Gwangju Institute of Science and Technology Gwangju Republic of KoreaAsan Institute for Life Sciences, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of KoreaAsan Institute for Life Sciences, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of KoreaDivision of Geriatrics, Department of Internal Medicine, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of KoreaDepartment of Biomedical Science and Engineering Gwangju Institute of Science and Technology Gwangju Republic of KoreaDepartment of Biomedical Science and Engineering Gwangju Institute of Science and Technology Gwangju Republic of KoreaDepartment of Biomedical Science and Engineering Gwangju Institute of Science and Technology Gwangju Republic of KoreaDivision of Geriatrics, Department of Internal Medicine, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of KoreaAsan Institute for Life Sciences, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of KoreaAsan Institute for Life Sciences, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of KoreaDivision of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of KoreaDivision of Geriatrics, Department of Internal Medicine, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of KoreaDepartment of Biomedical Science and Engineering Gwangju Institute of Science and Technology Gwangju Republic of KoreaDivision of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center University of Ulsan College of Medicine Seoul Republic of KoreaABSTRACT Background β2‐Microglobulin (B2M) has garnered considerable interest as a potential pro‐ageing factor, leading to speculation about its involvement in muscle metabolism and the development of sarcopenia, a key component of ageing phenotypes. To explore this hypothesis, we conducted a comprehensive investigation into the impact of B2M on cellular and animal muscle biology, as well as its clinical implications concerning sarcopenia parameters in older individuals. Methods In vitro myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. For in vivo research, C57BL/6 mice aged 3 months were intraperitoneally given 250 μg of B2M daily, and muscular alterations were assessed one month later. Human blood samples were obtained from 158 participants who underwent assessments of muscle mass and function at an outpatient geriatric clinic affiliated with a teaching hospital. Sarcopenia and associated parameters were assessed using cut‐off values specifically tailored for the Asian population. The concentration of serum B2M was quantified through an enzyme‐linked immunosorbent assay. Results Recombinant B2M inhibited in vitro myogenesis by increasing intracellular reactive oxygen species (ROS) production. Furthermore, B2M significantly induced differential myotube atrophy via ROS‐mediated ITGB1 downregulation, leading to impaired activation of the FAK/AKT/ERK signalling cascade and enhanced nuclear translocation of FoxO transcription factors. Animal experiments showed that mice with systemic B2M treatment exhibited significantly smaller cross‐sectional area of tibialis anterior and soleus muscle, weaker grip strength, shorter grid hanging time, and decreased latency time to fall off the rotating rod, compared to untreated controls. In a clinical study, serum B2M levels were inversely associated with grip strength, usual gait speed and short physical performance battery (SPPB) total score after adjustment for age, sex, and body mass index, whereas sarcopenia phenotype score showed a positive association. Consistently, higher serum B2M levels were associated with higher risk for weak grip strength, slow gait speed, low SPPB total score, and poor physical performance. Conclusion These results provide experimental evidence that B2M exerted detrimental effects on muscle metabolism mainly by increasing oxidative stress. Furthermore, we made an effort to translate the results of in vitro and animal research into clinical implication and found that circulating B2M could be one of blood‐based biomarkers to assess poor muscle health in older adults.https://doi.org/10.1002/jcsm.13745ageingbiomarkerpro‐ageing factorsarcopeniaβ2‐microglobulin |
| spellingShingle | Shibo Wei So Jeong Park Eunah Choi Il‐Young Jang Yan Zhang Yingqi Xue Yunju Jo Hee‐Won Jung Eunhye Ji Jin Young Lee Yujin Moon Eunju Lee Dongryeol Ryu Beom‐Jun Kim Detrimental Effects of β2‐Microglobulin on Muscle Metabolism: Evidence From In Vitro, Animal and Human Research Journal of Cachexia, Sarcopenia and Muscle ageing biomarker pro‐ageing factor sarcopenia β2‐microglobulin |
| title | Detrimental Effects of β2‐Microglobulin on Muscle Metabolism: Evidence From In Vitro, Animal and Human Research |
| title_full | Detrimental Effects of β2‐Microglobulin on Muscle Metabolism: Evidence From In Vitro, Animal and Human Research |
| title_fullStr | Detrimental Effects of β2‐Microglobulin on Muscle Metabolism: Evidence From In Vitro, Animal and Human Research |
| title_full_unstemmed | Detrimental Effects of β2‐Microglobulin on Muscle Metabolism: Evidence From In Vitro, Animal and Human Research |
| title_short | Detrimental Effects of β2‐Microglobulin on Muscle Metabolism: Evidence From In Vitro, Animal and Human Research |
| title_sort | detrimental effects of β2 microglobulin on muscle metabolism evidence from in vitro animal and human research |
| topic | ageing biomarker pro‐ageing factor sarcopenia β2‐microglobulin |
| url | https://doi.org/10.1002/jcsm.13745 |
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