The MicroRNA Content of Exosomes in the Context of Aging
Much of the communication between cells is carried in extracellular vesicles, membrane-wrapped packages of signaling molecules. Vesicles are classified by size at present, though the nomenclature is often used confusingly and inconsistently. Exosomes are one class of smaller and frequently studied vesicle. Since it is now comparatively cheap to analyze the contents of vesicles obtained from blood samples, there exists a wealth of data related to changes in vesicle sizes, types, and contents that take place with age. It remains to be seen as to what can be achieved with this data beyond the construction of biomarkers to measure biological age.
Almost every cell, including stem cells, naturally release extracellular vesicles (EVs) responsible for cell-to-cell communication. They are split into three categories: microvesicles or ectosomes are submicron vesicles with a diameter of 100nm-1000nm, distinguished by biogenesis mechanisms including cytoskeleton remodeling and phosphatidylserine externalization. These microvesicles are formed by the outward budding and fission of the plasma membrane after cell stimulation or stress. Exosomes are the most common EVs studied and the smallest ones with a diameter of 30nm-100nm.
Exosomes are considered key regulators of many biological settings and are present in several extracellular fluids to mediate cellular communication. Recently, they were suggested as biomarkers for several diseases to set up diagnosis and disease progression. Their characteristics hold a great interest in designing therapeutic purposes in metabolic and genetic disorders, neurodegenerative and cardiovascular diseases, and cancer.
The first signature of human aging is the decrease of tissue regeneration and repair, leading to the accumulation of senescent cells. These cells have been described to release more exosomes with different compositions than a normal cell. A cellular transcriptional program is induced whereby the number and composition of exosomes are changed, consequently reflecting the current parent cell profile. Much evidence has increasingly involved exosomes and exosome-derived miRNAs in both normal and pathological aging processes. Evidence has also increasingly involved exosome-derived miRNAs in aging-associated diseases. In this work, we review exosome biogenesis and its involvement in the mechanisms related to aging with a focus on the different pathways described for their secreted miRNAs.