Skeletal muscle of young females under resistance exercise exhibits a unique innate immune cell infiltration profile compared to males and elderly individuals
Paola Castrogiovanni, Cristina Sanfilippo, Rosa Imbesi, Giacomo Lazzarino, Giovanni Li Volti, Daniele Tibullo, Nunzio Vicario, Rosalba Parenti, Lazzarino Giuseppe, Ignazio Barbagallo, Amer M. Alanazi, Michele Vecchio, Francesco Cappello, Giuseppe Musumeci, Michelino Di Rosa
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Abstract
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.
期刊介绍：
The Journal of Muscle Research and Cell Motility has as its main aim the publication of original research which bears on either the excitation and contraction of muscle, the analysis of any one of the processes involved therein, the processes underlying contractility and motility of animal and plant cells, the toxicology and pharmacology related to contractility, or the formation, dynamics and turnover of contractile structures in muscle and non-muscle cells. Studies describing the impact of pathogenic mutations in genes encoding components of contractile structures in humans or animals are welcome, provided they offer mechanistic insight into the disease process or the underlying gene function. The policy of the Journal is to encourage any form of novel practical study whatever its specialist interest, as long as it falls within this broad field. Theoretical essays are welcome provided that they are concise and suggest practical ways in which they may be tested. Manuscripts reporting new mutations in known disease genes without validation and mechanistic insight will not be considered. It is the policy of the journal that cells lines, hybridomas and DNA clones should be made available by the developers to any qualified investigator. Submission of a manuscript for publication constitutes an agreement of the authors to abide by this principle.
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