Circular RNAs as a Potential Basis for Biomarkers of Aging
The presence and function of circular RNAs in cells is comparatively poorly understood. The expression levels of at least some circular RNAs appear to change with age. This suggests that, even without a full understanding of function, it might be possible to use this data as the basis for a biomarker of aging. It is already the case that other biomarkers of aging have been constructed from weighted combinations of age-related changes in the broader transcriptome of RNA expression. These join aging clocks built from epigenetic and proteomic data, all of which exhibit changes that are characteristic of age.
The commonality between all of these approaches is that it remains very unclear as to exactly how the causes of aging, the underlying forms of molecular damage, lead to specific changes in the epigenome, transcriptome, or proteome. These measures of biological age are black boxes at present, and thus hard to use as assessments for the effectiveness of any given approach to rejuvenation. Perhaps they reflect only a few of the mechanisms of aging, or give a great deal of weight to one over another, for example. We just don't know yet.
Circular RNAs (circRNAs), a novel type of universal and diverse endogenous transcripts that has been a recent focus in the transcriptomics field, were first observed through an electron microscope in the cytoplasm of eukaryotic cells in 1979. CircRNAs form covalently closed loop structures and are more stable than linear RNAs, insusceptible to degradation by RNA exonuclease or RNase R. Subsequent reports revealed that circRNAs can act as miRNA sponges, transcriptional regulators, binding partners of proteins, or even translated into functional proteins. Furthermore, circRNAs are abundant, relatively stable, specifically expressed in tissues, and evolutionary conserved among species, affording them the potential to be biomarkers for human diseases.
Recent studies have identified several circRNAs as regulators of various pathways that are involved in aging and cellular senescence. In particular, dysregulated circRNAs were implicated in the pathophysiology of age-related diseases, including cerebrovascular disease, neurodegenerative disease, cancer, diabetes, rheumatoid arthritis, and osteoporosis.
In recent years, circRNAs have gradually become one of the most prominent targets in the field of transcriptomics because of their critical roles in the regulation of gene expression and development of several diseases. The characteristic stability, abundance, and tissue-specific expression of circRNAs confer them great potential for use as biomarkers of various diseases. Notably, circRNAs can exist in the exosomes and plasma due to their excellent stability, thus, providing a more convenient way for diagnosing pathologies. Further investigations regarding the function and mechanism underlying the associations between circRNAs and age-related diseases are required.
Q: Can it be used as biomarker for other indications like cancer or transplant immune rejection?