17 2023 2023-05-10 10.3390/cimb45040204 Transposable elements are important sources of miRNA, long non-coding RNAs genes, and their targets in the composition of protein-coding genes in plants and animals. Therefore, the detection of expression levels of specific non-coding RNAs in various tissues and cells in normal and pathological conditions may indicate a programmed pattern of transposable elements’ activation. This reflects the species-specific composition and distribution of transposable elements in genomes, which underlie gene regulation in every cell division, including during aging. TEs’ expression is also regulated by epigenetic factors (DNA methylation, histone modifications), SIRT6, cytidine deaminases APOBEC3, APOBEC1, and other catalytic proteins, such as ERCC, TREX1, RB1, HELLS, and MEGP2. In evolution, protein-coding genes and their regulatory elements are derived from transposons. As part of non-coding regions and introns of genes, they are sensors for transcriptional and post-transcriptional control of expression, using miRNAs and long non-coding RNAs, that arose from transposable elements in evolution. Methods (Orbld, ncRNAclassifier) and databases have been created for determining the occurrence of miRNAs from transposable elements in plants (PlanTE-MIR DB, PlaNC-TE), which can be used to design epigenetic gene networks in ontogenesis. Based on the data accumulated in the scientific literature, the presence of 467 transposon-derived miRNA genes in the human genome has been reliably established. It was proposed to create an updated and controlled online bioinformatics database of miRNAs derived from transposable elements in healthy individuals, as well as expression changes of these miRNAs during aging and various diseases, such as cancer and difficult-to-treat diseases. The use of the information obtained can open new horizons in the management of tissue and organ differentiation to aging slow down. In addition, the created database could become the basis for clarifying the mechanisms of pathogenesis of various diseases (imbalance in the activity of transposable elements, reflected in changes in the expression of miRNAs) and designing their targeted therapy using specific miRNAs as targets. This article provides examples of the detection of transposable elements-derived miRNAs involved in the development of specific malignant neoplasms, aging, and idiopathic pulmonary fibrosis. https://repo.bashgmu.ru/publication/2549 https://repo.bashgmu.ru/files/2725