Researchers have made significant strides in understanding how extracellular vesicles (EVs) from stem cells can combat cellular senescence, particularly through a study published in the journal Aging Cell.

The study revealed that no single micro-RNA (miRNA) was fully effective on its own; however, a combination of four specific miRNAs, designated as E5, showed broad positive effects on senescent fibroblasts, outperforming the benefits of EVs from embryonic stem cells (AC83).

The researchers specifically examined fibroblasts that had been induced into senescence and found that stem cell-derived EVs, especially those from AC83, significantly reduced the proportion of senescent cells from 100% to approximately 70%.

Genetic investigations indicated that the E5 combination downregulated genes PCAF and HIPK2, which are involved in initiating the senescence response, effectively blocking pathways that lead to senescence.

Through analysis of the micro-RNAs extracted from the EVs, researchers identified eight specific miRNAs that could contribute to the observed benefits and began to explore effective combinations of these miRNAs.

In addition to AC83, EVs from other stem cell types, including endothelial stem cells and human liver stem cells, were tested, revealing varying degrees of effectiveness, with AC83 being the most effective overall.

All types of EVs studied were classified as senomorphic, meaning they altered the behavior of senescent cells without significantly reducing overall cell numbers.

Extracellular vesicles are signaling molecules that carry components, such as micro-RNAs, capable of influencing cellular behavior, and previous research has highlighted their potential in treating various conditions.

In vivo testing on two-year-old mice demonstrated that injecting the E5 combination resulted in reduced markers of senescence and DNA damage in liver tissue, alongside trending reductions in inflammation markers.

Despite promising results, the study notes that more research is needed to explore the full range of effects of these miRNAs on different cell types and their potential in lifespan extension compared to traditional senolytic or senomorphic treatments.

Traditional approaches to combating senescence include senolytics, which eliminate senescent cells, and senomorphics, which alter their behavior; this study introduces EVs as a novel method to address the issue.