268P Age and sex affect human skeletal muscle secretome

• Published in: Neuromuscular disorders : NMD Vol. 43; p. 104441
• Main Authors: Crisol, B., Pinzon, N., Orio, J., Gaut-Serey, L., Ohana, J., Bensalah, M., Peterson, C., Butler-Browne, G., Mouly, V., Bigot, A., Trollet, C.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-10-2024
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2024.07.086

Aging is a gradual decline in physiological well-being, resulting in diminished tissue functionality. During aging, skeletal muscle strength and mass decrease and this is accompanied by a decrease in regenerative capacity. Muscle is a secretory organ capable of regulating its own function and/or influencing the activity of other tissues via myokines. In this context, how muscle secretion is modified during aging and how this affects muscle regeneration and homeostasis is still not known. Here, combining bioinformatic analysis and in vitro experiments we have identified alterations in the secretome of human muscle cells during aging. We have analyzed the medium of differentiated muscle cells isolated from muscles of young and old human subjects by proteomic approaches and we have identified 127 proteins differentially secreted between the young and old samples. The old cells presented already known aging phenotypes, as increased in the lipids stock, defect in differentiation and impaired mitochondrial function. Interestingly, more proteins are increasingly secreted upon aging than less secreted, suggesting that old cells adapt to aging mainly by modifying its secretion. In parallel, it is known that men and women respond differently to muscle aging and present different DNA methylation and gene expression profiles. Here we also identified that the secreted proteins were also affected by the sex-bias, especially in the young donors’ samples. Using in silico transcriptome analyses from men and women using the Genotype-Tissue Expression study of young adults (12 females and 30 males) and older adults (6 females and 12 males) we observed that besides age, sex acts as a major source of variation in the muscle transcriptome. Taking sex as an important factor, we identified in our data that sex affects muscle secretome, but not muscle proteome. Altogether, these results suggest that aging and sex difference have major effects in the muscle secretome and now we aim to identify specific targets to reduce the effects of muscle aging in the elderly, by testing in vitro the proteins of interest identified in the muscle secretome.