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Skeletal muscle of young females under resistance exercise exhibits a unique innate immune cell infiltration profile compared to males and elderly individuals

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Journal of Muscle Research and Cell Motility Aims and scope Submit manuscript


Muscle damage resulting from physical activities such as exercise triggers an immune response crucial for tissue repair and recovery. This study investigates the immune cell profiles in muscle biopsies of individuals engaged in resistance exercise (RE) and explores the impact of age and sex on the immune response following exercise-induced muscle damage. Microarray datasets from muscle biopsies of young and old subjects were analyzed, focusing on the gene expression patterns associated with immune cell activation. Genes were compared with immune cell signatures to reveal the cellular landscape during exercise. Results show that the most significant modulated gene after RE was Folliculin Interacting Protein 2 (FNIP2) a crucial regulator in cellular homeostasis. Moreover, the transcriptome was stratified based on the expression of FNIP2 and the 203 genes common to the groups obtained based on sex and age. Gene ontology analysis highlighted the FLCN-FNIP1-FNIP2 complex, which exerts as a negative feedback loop to Pi3k-Akt-mTORC1 pathway. Furthermore, we highlighted that the young females exhibit a distinct innate immune cell activation signature compared to males after a RE session. Specifically, young females demonstrate a notable overlap with dendritic cells (DCs), M1 macrophages, M2 macrophages, and neutrophils, while young males overlap with M1 macrophages, M2 macrophages, and motor neurons. Interestingly, in elderly subjects, both sexes display M1 macrophage activation signatures. Comparison of young and elderly signatures reveals an increased M1 macrophage percentage in young subjects. Additionally, common genes were identified in both sexes across different age groups, elucidating biological functions related to cell remodeling and immune activation. This study underscores the intricate interplay between sex, age, and the immune response in muscle tissue following RE, offering potential directions for future research. Nevertheless, there is a need for further studies to delve deeper and confirm the dynamics of immune cells in response to exercise-induced muscle damage.

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The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.


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We would like to show our gratitude to the authors of microarray datasets made available online, for consultation and re-analysis. We would like to thank Ludovico Einaudi for inspiring us to write this manuscript.


The author Michelino Di Rosa was supported by the University Research Project Grant (PIACERI 2020–2022), Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Italy. The author Amer M. Alanazi was funded by the researchers supporting project number (RSP2024R261) King Saud University, Riyadh, Saudi Arabia. The funder/sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Conceptualization, M.D.; Methodology, M.D. P.C., and C.S.; Investigation, C.S., P.C., M.D.; Data Curation, G.LV., R.I., G.L., D.T., N.V., R.P., L.G., I.B., A,M.A., V.M., F.C.; Writing – Original Draft, M.D., P.C, and C.S.; Writing - Visualization, M.D.; Supervision, M.D., G.M.

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Correspondence to Michelino Di Rosa.

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Castrogiovanni, P., Sanfilippo, C., Imbesi, R. et al. Skeletal muscle of young females under resistance exercise exhibits a unique innate immune cell infiltration profile compared to males and elderly individuals. J Muscle Res Cell Motil (2024).

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