Circulating microRNAs related to lipid metabolism and solid tissue maintenance and morphology associate with mortality in elderly twins.

The lifespan of humans varies greatly between individuals. Here, we aimed to explore what biological roles miRNAs may have on old age mortality-variation. Circulating miRNAs were measured in plasma from 43 monozygotic twin pairs (73-95 years of age) and mortality analyses were applied using Cox regression survival analyses and linear regression analyses of lifespan. In general, nominally significant miRNAs were mainly upregulated with shorter lifespan, both in Cox analysis (72 % upregulated) and in linear regression analysis (81 % upregulated). A total of 29 miRNAs were associated to mortality at a nominal significance level (p < 0.05) in the survival analysis, but no miRNAs passed the FDR adjusted level of significance. Seven of the 29 miRNAs; hsa-miR-140-3p, hsa-miR-16-5p, hsa-miR-487b-3p, hsa-miR-19a-3p, hsa-let-7d-5p, hsa-miR-320a, hsa-miR-375, were nominally significant across two linear twin-paired analyses and the cox analysis. Pathway analyses of the 29 nominally significant miRNAs from the individual level analyses resulted in two nominally significant associated Reactome pathways (unadjusted p < 0.05); 'Negative regulation of FGFR signaling' and 'Neurotransmitter receptor binding and downstream transmission in the postsynaptic cell', and two significantly associated KEGG pathways; 'Linoleic acid metabolism' and 'Toxoplasmosis'. Additional pathway analyses and results of previous studies support that miRNAs linked to mortality at age 70 years or older play a role in lipid metabolism, tissues maintenance and morphology.