Epigenetic mechanisms of peptidergic regulation of gene expression during aging of human cells

Abstract

Expression levels of genes encoding specific transcription factors and other functionally important proteins vary upon aging of pancreatic and bronchial epithelium cell cultures. The peptides KEDW and AEDL tissue-specifically affect gene expression in pancreatic and bronchial cell cultures, respectively. It is established in this work that the DNA methylation patterns of the PDX1, PAX6, NGN3, NKX2-1, and SCGB1A1 gene promoter regions change upon aging in pancreatic and bronchial cell cultures in correlation with variations in their expression levels. Thus, stable changes in gene expression upon aging of cell cultures could be caused by changes in their promoter methylation patterns. The methylation patterns of the PAX4 gene in pancreatic cells as well as those of the FOXA1, SCGB3A2, and SFTPA1 genes in bronchial cells do not change upon aging and are unaffected by peptides, whereas their expression levels change in both cases. The promoter region of the FOXA2 gene in pancreatic cells contains a small number of methylated CpG sites, their methylation levels being affected by cell culture aging and KEDW, though without any correlation with gene expression levels. The promoter region of the FOXA2 gene is completely unmethylated in bronchial cells irrespective of cell culture age and AEDL action. Changes in promoter methylation might be the cause of age- and peptide-induced variations in expression levels of the PDX1, PAX6, and NGN3 genes in pancreatic cells and NKX2-1 and SCGB1A1 genes in bronchial cells. Expression levels of the PAX4 and FOXA2 genes in pancreatic cells and FOXA1, FOXA2, SCGB3A2, and SFTPA1 genes in bronchial cells seem to be controlled by some other mechanisms.

Peptides as epigenetic modulators: therapeutic implications

“…These compounds exert a variety of functions in the human body and are able to modulate epigenetic mechanisms. There are different reports discussing gene regulatory effects of peptides [55–58]. Depending on the peptide, these effects are direct or indirect by binding to receptors and activation of intracellular signaling cascades (Table 1).…”

“…These short “cryptic” peptides can be formed endogenously by proteolytic cleavage of nuclear proteins or by synthesis after which they penetrate the cytoplasmic and nuclear membrane [60, 61]. These peptides are involved in the epigenetic regulation of aging and can have health-promoting effects by for example suppressing age-related increased expression of matrix metalloproteases and caspase-dependent apoptosis [55, 93].…”

Neuroepigenetic Mechanisms of Action of Ultrashort Peptides in Alzheimer’s Disease

“…Previous studies have suggested an epigenetic mechanism of action of ultrashort peptides [17][18][19][20]. In this regard, the aim of the review is to analyze the possible epigenetic mechanisms of the neuroprotective action of short peptides in AD.…”

Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line

“…Their main function is a normalizing effect on specific organs, replacing or supporting the activity of substances secreted by these morphological structures. They also increase the lifespan of mesenchymal stem cell (MCS) and induce molecular mechanisms that contrast senescence [ 25 ]. They modulate neuronal activity and hinder cognitive degeneration, probably by improving the integration of cellular functions, and thus counteracting the accumulation of free radicals.…”