Circulating MicroRNAs and Life Expectancy Among Identical Twins

Abstract

Summary Human life expectancy is influenced not only by longevity assurance mechanisms and disease susceptibility loci but also by the environment, gene-environment interactions, and chance. MicroRNAs (miRNAs) are a class of small noncoding RNAs closely related to genes. Circulating microRNAs have been shown as promising non-invasive biomarkers in the development of many pathophysiological conditions. However, the concentration of miRNA in the circulation may also be affected by environmental factors. We used a next-generation sequencing platform to assess the association of circulating miRNA with life expectancy, for which deaths are due to all causes independent of genes. In addition, we showed that miRNAs are present in 41-year archived plasma samples, which may be useful for both life expectancy and all-cause mortality risk assessment. Plasma miRNAs from nine identical male twins were profiled using next-generation sequencing. The average absolute difference in the minimum life expectancy was 9.68 years. Intra-class correlation coefficients were above 0.4 for 50% of miRNAs. Comparing deceased twins with their alive co-twin brothers, the concentrations were increased for 34 but decreased for 30 miRNAs. Identical twins discordant in life expectancy were unlike in the majority of miRNAs, suggesting that environmental factors are pivotal in miRNAs related to life expectancy.

The Role of microRNAs in Organismal and Skin Aging

“…Many miRNAs have been previously demonstrated to be differentially expressed in cells, tissues, whole blood [ 10 , 73 , 74 , 75 ], plasma [ 76 , 77 , 78 ], and serum [ 79 , 80 , 81 ] in relation to age.…”

“…The analysis of plasma circulating miRNA from a twin study conducted by the National Heart, Lung, and Blood Institute identified significantly up-regulated miR-3615 and miR-619 in younger deceased twins compared to their longer-lived co-twin. Additionally, the increased expression of miR-423-5p and miR-4305 was detected in less than 70% of short-lived twins [ 76 ]. In this study, changes in the remaining longevity-related miRNAs were not significant, potentially due to a small sample size.…”

Micro-RNA signatures in monozygotic twins discordant for congenital heart defects

“…Moreover, we had to incorporate CHD of different morphological and clinical types and severity, due to the low incidence of monozygotic twins discordant for CHD. Since it has been shown that even non-CHD monozygotic twins display a considerable variation of their miRNA fingerprints [29], we were prepared to encounter a highly complex and heterogeneous picture. It is a challenge to recruit and assay monozygotic twins and even collect data for a given phenotype.…”

MicroRNAs: An Update of Applications in Forensic Science

“…miRNAs have been investigated as biomarkers for MZ twins’ identification because several studies reported some disease-related miRNAs as differentially expressed in MZ twins [ 114 , 115 , 116 ].…”