Common diseases alter the physiological age-related blood microRNA profile

Abstract

Aging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in age-related microRNAs by analyzing whole blood from 1334 healthy individuals. We observed a larger influence of the age as compared to the sex and provide evidence for a shift to the 5’ mature form of miRNAs in healthy aging. The addition of 3059 diseased patients uncovered pan-disease and disease-specific alterations in aging profiles. Disease biomarker sets for all diseases were different between young and old patients. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile. Altogether, these data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers.

miRTargetLink 2.0—interactive miRNA target gene and target pathway networks

“…miRNA expression is known to depend on the physiological or pathophysiological contexts. For example, the age of unaffected individuals or patients with different diseases can affect miRNA expression ( 33 ). Cholinergic-targeting noncoding RNAs, miRNAs or lncRNAs can also modulate sex-specific- and age-related acetylcholine signals ( 34 ).…”

Circulating miR‐19a‐3p and miR‐19b‐3p characterize the human aging process and their isomiRs associate with healthy status at extreme ages

“…Furthermore, they are recognized as mediators of "inflammaging," a term used to describe the ageassociated chronic inflammation, and they can be considered as important members of the senescence-associated secretory phenotype (SASP) (Franceschi et al, 2017;Olivieri et al, 2013a;Terlecki-Zaniewicz et al, 2018). In fact, some c-miRs are aberrantly regulated upon aging and during ARD-GS (Fehlmann et al, 2020;Hackl et al, 2017;Heilmeier et al, 2016;Jung & Suh, 2014;Olivieri et al, 2013b); thus, they are powerful epigenetic biomarkers to trace aging/ARD-GS and longevity, as recently suggested by our team (Olivieri et al, 2017).…”

Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications

“…MiRNA is a small RNA with a length of about 20-24 nucleotides, which can bind to mRNA and regulate the expression of multiple target genes. It plays a vital role in immune regulation, insulin secretion, cell differentiation, and other physiological and pathological processes ( 122 , 123 ). Exosomal nucleic acids exist in a remarkably stable form due to the protective effects of exosomes from RNase activity.…”