Abstract
The intestinal epithelium serves as a dynamic barrier to protect the host tissue from exposure to a myriad of inflammatory stimuli in the luminal environment. Intestinal epithelial cells (IECs) encompass differentiated and specialized cell types that are equipped with regulatory genes, which allow for sensing of the luminal environment. Potential inflammatory cues can instruct IECs to undergo a diverse set of phenotypic alterations. Aging is a primary risk factor for a variety of diseases; it is now well-documented that aging itself reduces the barrier function and turnover of the intestinal epithelium, resulting in pathogen translocation and immune priming with increased systemic inflammation. In this study, we aimed to provide an effective epigenetic and regulatory outlook that examines age-associated alterations in the intestines through the profiling of microRNAs (miRNAs) on isolated mouse IECs. Our microarray analysis revealed that with aging, there is dysregulation of distinct clusters of miRNAs that was present to a greater degree in small IECs (22 miRNAs) compared to large IECs (three miRNAs). Further, miRNA–mRNA interaction network and pathway analyses indicated that aging differentially regulates key pathways between small IECs (e.g., toll-like receptor-related cascades) and large IECs (e.g., cell cycle, Notch signaling and small ubiquitin-related modifier pathway). Taken together, current findings suggest novel gene regulation pathways by epithelial miRNAs in aging within the gastrointestinal tissues.
Highlights
Aging is a risk factor for many chronic diseases and contributes to systemic disruptions that increase the prevalence of illness [1]
The intestinal epithelium plays a crucial role in mediating the crosstalk between the microbiome and the immune system within host tissue [15,16]
Lipopolysaccharide-induced TLR4 signaling cascades were shown to repress the expression of the let-7 family and rescue cytokine production of IL-6 and IL-10, both of which are critical in bacterial infection [38]
Summary
Aging is a risk factor for many chronic diseases and contributes to systemic disruptions that increase the prevalence of illness [1]. Recent studies have shown that aging induces a low-grade chronic inflammation referred to as “inflammaging”, which is associated with poorer functional recovery following the onset of acute injuries in the elderly [6]. Such age-induced functional decline, especially within the gastrointestinal (GI) tract and its local immune system, directly contributes to higher rates of systemic inflammation and infection [7,8]. Understanding the mechanisms of tissue senescence regulated by epigenetic and cellular pathways is essential for the development of novel therapeutic strategies to treat age-related diseases
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