Researchers here note that circular RNAs are differentially expressed in long-lived individuals. This assessment is very much a first step on the lengthy road of determining whether or not circular RNAs are interesting in the context of aging and longevity. Since everything is connected to everything else in cellular biochemistry, an exceedingly complex web of interactions, most of the observed differences between long-lived people and others will be unimportant downstream effects, not directly connected to aging and longevity. Further, present evidence suggests that environmental and lifestyle factors are by far the greatest determinant of variations in human longevity; the search for mechanisms of longevity arising from genetic variants within our species will likely produce little of value.
Recent studies suggested that noncoding RNAs are involved in healthy aging and/or age-related diseases. It remains, however, largely unknown whether circular RNAs (circRNAs), a class of endogenous noncoding RNA with a covalently closed continuous loop predominantly generated from back-splicedback-spliced exons, and acting as 'microRNA sponges' or 'scaffolding' for RNA-binding protein, in human longevity. Increasing evidence has revealed the crucial roles of circRNAs in multiple biological processes and even in human diseases. For instance, several circRNAs were related with age-related diseases, including neurodegenerative diseases, cardiovascular diseases, type 2 diabetes, and, even, cancers. Nevertheless, their roles in the process of human lifespan extension are largely unexplored.
In this study, we investigated the circRNAs expression pattern of longevous families, from a Chinese cohort of longevity. Based on weighted circRNA co-expression network analysis, we found that longevous elders (98.3 ± 3.4 years) specifically gained eight but lost seven conserved circRNA-circRNA co-expression modules compared with normal elder controls (spouses of offspring of long-lived individuals, age = 59.3 ± 5.8 years). Both the gained and lost module-related genes were enriched in infectious disease-related pathways. This suggests that these elders might have a history of infection, which could be related to life in the early and middle twentieth century when medical health care was poorer and contagious diseases were prevalent. It seems that these circRNAs may be associated with previous responses to infectious diseases.
Given that these modules, as predicted by mRNA-circRNA co-expression analysis, were closely related to processes involved in lifespan extension, the gain and loss of these circRNA-circRNA co-expression modules in very long-lived individuals are unlikely to be a random process but rather contribute to healthy human aging and may represent a new target for the regulation of healthy human aging.