“Taken together, these results indicate that EVs and their miRNA cargo may be potential contributors to the SASP and senescence-associated signalling in skeletal muscle during advanced aging.”

BUFFALO, NY — June 3, 2026 — A new research paper was published in Volume 18 of Aging-US on May 15, 2026, titled “Extracellular vesicles released by senescent myoblasts affect recipient cells via miRNA-target interactions.”

The study was led by first author Michael Kamal from the Department of Kinesiology at McMaster University and corresponding author Gianni Parise from the same university.

As people age, skeletal muscle gradually loses strength, size, and regenerative capacity. Scientists have increasingly linked these changes to cellular senescence—a state in which damaged cells permanently stop dividing but remain metabolically active. These senescent cells release a complex mixture of signaling molecules known as the senescence-associated secretory phenotype (SASP), which can influence neighboring cells and contribute to tissue dysfunction.

In this study, the researchers investigated whether extracellular vesicles (EVs)—tiny membrane-bound particles released by cells—play a role in this process. Specifically, they examined EVs released by senescent muscle precursor cells, known as myoblasts, and analyzed the microRNAs (miRNAs) carried within these vesicles.

The team found that senescent myoblasts released factors that impaired normal muscle cell development. When healthy muscle cells were exposed to signals from senescent cells, the resulting muscle fibers became significantly smaller and displayed increased expression of genes associated with cellular stress and senescence.

Further analysis revealed that EVs released by senescent myoblasts carried a distinct set of miRNAs. The researchers identified 22 significantly altered miRNAs, including several previously linked to cellular senescence, such as miR-34a, miR-34b, miR-34c, and miR-22. The study also identified miR-301a-3p as a potentially novel senescence-associated miRNA.

Using bioinformatics and laboratory experiments, the investigators showed that these vesicle-associated miRNAs targeted genes involved in cell-cycle regulation, apoptosis, autophagy, and DNA damage responses. When EVs from senescent cells were transferred to healthy myoblasts, they altered the expression of several important genes, including Mdm2 and Pten, both of which are involved in cellular survival and stress-response pathways.

To explore whether these findings might be relevant to aging muscle, the researchers compared their results with previously published RNA sequencing data from young and aged mouse muscle. They discovered substantial overlap between genes targeted by senescence-associated EV miRNAs and genes that change during muscle aging, suggesting that these vesicles may help shape the aging muscle environment.

“Overall, the results of this study suggest that the miRNA cargo of EVs has the potential to regulate senescent gene expression and may contribute to some of the aging-related perturbations in the muscle transcriptome.”

Interestingly, the EVs did not immediately trigger a full senescence program in recipient cells. Instead, the findings suggest that these vesicles may prepare neighboring cells for future stress responses by promoting survival-related signaling pathways before other senescence-associated factors exert their effects.

The authors propose that extracellular vesicles may represent an underappreciated component of how senescent cells communicate within aging skeletal muscle. By carrying specific miRNAs that regulate hundreds of genes, these vesicles may contribute to the molecular changes that accompany age-related muscle deterioration.

Together, the findings offer new insight into how senescent muscle cells influence surrounding tissues and point to extracellular vesicles as potential mediators of age-related signaling. These findings may help advance future research aimed at understanding—and potentially slowing—the biological processes that contribute to muscle aging and sarcopenia.

Paper DOI: https://doi.org/10.18632/aging.206379               

Corresponding author: Gianni Parise – [email protected]

Keywords: aging, cellular senescence, extracellular vesicles, myoblasts, miRNA, multi-omics

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