Exosomes in Harmful Senescent Cell Signaling

Extracellular vesicles such as exosomes are an important component of cell signaling, small membrane-bound packages of molecules that are passed around in large numbers by cell populations. The presence of lingering senescent cells is one of the root causes of aging. These errant cells never make up more than a small fraction of the overall cell population, even in very late life, but they cause considerable disruption and harm through the inflammatory signaling that they generate. Extracellular vesicles are here, as elsewhere, an important part of that signaling process.

Given that the most straightforward path towards therapy is the destruction of senescent cells, there probably isn't all that much that can be accomplished therapeutically more rapidly and effectively via a focus on exosomes. As authors of this open access paper point out, however, it is still a potentially useful area of research from the point of view of expanding knowledge of the fundamental biology of aging, how aging progresses in detail. Given that senescent cells accelerate dysfunction, and given that they do this via signaling, mapping that signaling in greater detail will probably teach us something.

Communication between cells is quintessential for biological function and cellular homeostasis. Membrane-bound extracellular vesicles known as exosomes play pivotal roles in mediating intercellular communication in tumor microenvironments. These vesicles and exosomes carry and transfer biomolecules such as proteins, lipids, and nucleic acids. Here we focus on exosomes secreted from senescent cells.

Cellular senescence can alter the microenvironment and influence neighbouring cells via the senescence-associated secretory phenotype (SASP), which consists of factors such as cytokines, chemokines, matrix proteases, and growth factors. This review focuses on exosomes as emerging SASP components that can confer pro-tumorigenic effects in pre-malignant recipient cells. This is in addition to their role in carrying SASP factors. Transfer of such exosomal components may potentially lead to cell proliferation, inflammation, and chromosomal instability, and consequently cancer initiation.

Senescent cells are known to gather in various tissues with age; eliminating senescent cells or blocking the detrimental effects of the SASP has been shown to alleviate multiple age-related phenotypes. Hence, we speculate that a better understanding of the role of exosomes released from senescent cells in the context of cancer biology may have implications for elucidating mechanisms by which aging promotes cancer and other age-related diseases, and how therapeutic resistance is exacerbated with age.

Link: https://doi.org/10.3390/ijms20102547