Aging of the mammalian gastrointestinal tract: a complex organ system

Abstract

Gastrointestinal disorders are a major cause of morbidity in the elderly population. The gastrointestinal tract is the most complex organ system; its diverse cells perform a range of functions essential to life, not only secretion, digestion, absorption and excretion, but also, very importantly, defence. The gastrointestinal tract acts not only as a barrier to harmful materials and pathogens but also contains the vast number of beneficial bacterial populations that make up the microbiota. Communication between the cells of the gastrointestinal tract and the central nervous and endocrine systems modifies behaviour; the organisms of the microbiota also contribute to this brain–gut–enteric microbiota axis. Age-related physiological changes in the gut are not only common, but also variable, and likely to be influenced by external factors as well as intrinsic aging of the cells involved. The cellular and molecular changes exhibited by the aging gut cells also vary. Aging intestinal smooth muscle cells exhibit a number of changes in the signalling pathways that regulate contraction. There is some evidence for age-associated degeneration of neurons and glia of the enteric nervous system, although enteric neuronal losses are likely not to be nearly as extensive as previously believed. Aging enteric neurons have been shown to exhibit a senescence-associated phenotype. Epithelial stem cells exhibit increased mitochondrial mutation in aging that affects their progeny in the mucosal epithelium. Changes to the microbiota and intestinal immune system during aging are likely to contribute to wider aging of the organism and are increasingly important areas of analysis. How changes of the different cell types of the gut during aging affect the numerous cellular interactions that are essential for normal gut functions will be important areas for future aging research.

Analysis of Cell Turnover in the Bronchiolar Epithelium Through the Normal Aging Process

“…In general, histological studies have also shown an age-related thinning of the human olfactory epithelium [26,27]. In contrast, observations in the age-associated changes in the architecture of the intestinal epithelium have not been consistent [28].…”

Comparison of Changes in the Interstitial Cells of Cajal and Neuronal Nitric Oxide Synthase-positive Neuronal Cells With Aging Between the Ascending and Descending Colon of F344 Rats

“…It is controversial whether age-related dysmotility is due to a decrease in the amount of smooth muscle cells themselves or to damage to intermediate cells such as neurons and ICCs. [45][46][47][48] ICCs play an important part in colonic motility: propulsion is considered to be induced by ICCs in the submucosal plexus, and the ICCs in muscle layers are thought to mediate between the nerves and the smooth muscle cells. 49 According to a previous human study and the present study, the concentration of ICCs seems to decrease in old age.…”

Nipped-A regulates intestinal stem cell proliferation in Drosophila

“…During aging, there is a progressive loss of intestinal homeostasis leading to impaired function and a higher probability of developing diseases such as cancer. One of the reasons for the loss of tissue homeostasis in mammals is speculated to be an altered stem cell behavior (Kirkwood, 2004;Saffrey, 2014); however, the exact effects of aging on the number and function of intestinal stem cells remains largely unclear. In recent years, Drosophila has become a prominent model organism to study mechanisms of regeneration and aging in the intestine (Jasper, 2015).…”