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Cardiac troponin T and autoimmunity in skeletal muscle aging

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Abstract

Age-related muscle mass and strength decline (sarcopenia) impairs the performance of daily living activities and can lead to mobility disability/limitation in older adults. Biological pathways in muscle that lead to mobility problems have not been fully elucidated. Immunoglobulin G (IgG) infiltration in muscle is a known marker of increased fiber membrane permeability and damage vulnerability, but whether this translates to impaired function is unknown. Here, we report that IgG1 and IgG4 are abundantly present in the skeletal muscle (vastus lateralis) of ~ 50% (11 out of 23) of older adults (> 65 years) examined. Skeletal muscle IgG1 was inversely correlated with physical performance (400 m walk time: r = 0.74, p = 0.005; SPPB score: r =  − 0.73, p = 0.006) and muscle strength (r =  − 0.6, p = 0.05). In a murine model, IgG was found to be higher in both muscle and blood of older, versus younger, C57BL/6 mice. Older mice with a higher level of muscle IgG had lower motor activity. IgG in mouse muscle co-localized with cardiac troponin T (cTnT) and markers of complement activation and apoptosis/necroptosis. Skeletal muscle–inducible cTnT knockin mice also showed elevated IgG in muscle and an accelerated muscle degeneration and motor activity decline with age. Most importantly, anti-cTnT autoantibodies were detected in the blood of cTnT knockin mice, old mice, and older humans. Our findings suggest a novel cTnT-mediated autoimmune response may be an indicator of sarcopenia.

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Acknowledgements

We thank Dr. Carol Milligan and Dr. Osvaldo Delbono for reading and discussing the paper.

Funding

This work was supported by the R21AG059180 and R21AG060037 (T. Z.), Wake Forest Claude D. Pepper Older Americans Independence Center P30-AG21332 (S. K.), and R01AG020583 (B. N.). Medifast provided the meal replacements used in the SILVER study, which was supported by Wake Forest Claude D. Pepper Older Americans Independence Center and Wake Forest University Translational Science Center.

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Correspondence to Tan Zhang.

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All subjects gave their informed consent for inclusion before they participated in the IMFIT and SILVER studies.

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All study participants consent for publication of data generate from the IMFIT and SILVER studies.

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The authors declare no competing interests.

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Zhang, T., Feng, X., Dong, J. et al. Cardiac troponin T and autoimmunity in skeletal muscle aging. GeroScience 44, 2025–2045 (2022). https://doi.org/10.1007/s11357-022-00513-7

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  • DOI: https://doi.org/10.1007/s11357-022-00513-7

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