Extracellular RNA in aging

Abstract

Since the discovery of extracellular RNA (exRNA) in circulation and other bodily fluids, there has been considerable effort to catalog and assess whether exRNAs can be used as markers for health and disease. A variety of exRNA species have been identified including mRNA, and non-coding RNA (ncRNA) such as microRNA (miRNA), small nucleolar RNA (snRNA), transfer RNA (tRNA), and long non-coding RNA (lncRNA). Age-related changes in exRNA abundance have been observed, and it is likely some of these transcripts play a role in aging. In this review, we summarize the current state of exRNA profiling in various body fluids and discuss age-related changes in exRNA abundance that have been identified in humans and other model organisms. MiRNAs, in particular, are a major focus of current research and we will highlight and discuss the potential role specific miRNAs might play in age-related phenotypes and disease. We will also review challenges facing this emerging field and various strategies that can be used for the validation and future use of exRNAs as markers of aging and age-related disease.

Extracellular RNA profiles with human age

“…We used DESeq2 to analyze differentially expressed miRNAs between young and old and identified 12 miRNAs that were significantly different between age groups. Recently, we analyzed existing studies in the literature to identify a number of circulating miRNAs that change with age in multiple studies (Dluzen et al., 2017). Here, we chose these miRNAs to further validate in this independent cohort (miR‐25‐3p, miR‐92a‐3p, miR‐93‐5p, miR‐101‐3p, miR‐106b‐5p, miR‐142‐5p, miR‐151a‐3p, and miR‐181a‐5p).…”

“…We chose to validate miRNAs that we identified in our DESeq2 analysis to be differentially expressed with age. For a cross‐study comparison, we chose many miRNAs that previously our group and others found to be changed with age (Dluzen et al., 2017; Noren Hooten et al., 2013). Many of these miRNAs significantly changed with age in serum in our study.…”

“…ExRNAs have been identified in most bodily fluids including plasma, serum, urine, saliva, and cerebrospinal fluid [for review see (Dluzen, Noren Hooten & Evans, 2017)]. In general, the most well‐studied biotype of exRNA has been microRNAs (miRNAs), but other noncoding RNAs (ncRNAs) are also present in extracellular fluids including Piwi‐interacting RNAs (piRNAs), long noncoding RNAs (lncRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), Y‐RNAs, and circular RNAs (circRNAs) (Amorim et al., 2017; Wei et al., 2017; Yeri et al., 2017).…”

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

“…In addition, given that miRNAs mostly function as intra-cellular modulators of mRNAs, their concentration in whole blood might be a poor indicator of their physiological effects. Nonetheless, miR-25–3p, miR-92a-3p, miR-93–5p, miR-101–3p, miR-106b-5p, miR-142–5p, miR-151a-3p, and miR-181a-5p tend to be under-represented, whereas miR-21–5p and miR-126–3p are over-represented at older ages 47,49,50 . Age-related changes in miRNAs have been suggested to contribute to inflammageing.…”

Exosomal long noncoding RNAs in aging and age‐related diseases

“…Accumulated evidence suggests that lncRNAs enter recipient cells through exosomes and participate in the regulation of aging and age‐related diseases (Table ). In a study on changes in exosome abundance with age, 15 RNA transcripts were found to increase with age, including three lncRNAs (EHHADH‐AS1, RP11‐696N14.1, and AC022311.1) . However, it needs to be further clarified whether these lncRNAs are involved in the regulation of aging.…”