Small Bowel Enterocyte Apoptosis and Proliferation Are Increased in the Elderly

Abstract

Background: It is known that in the elderly the small bowel does not reveal structural and functional deteriorations in normal conditions, whereas the absorptive function is impaired in stress conditions. Objective: The balance between enterocyte apoptosis and proliferation being responsible for the maintenance of tissue size, mucosal morphology and function in the gastrointestinal tract, the aim of our study was to evaluate the rates of enterocyte apoptosis and proliferation in the duodenal mucosa of aged human beings in comparison to adults. Methods: For this purpose, the terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end labelling (TUNEL) technique and immunohistochemistry for MIB-1 detection were applied on histological sections of endoscopic duodenal biopsy specimens obtained from 12 healthy elderly subjects (mean age 77.6 years; M/F 7/5) and 12 healthy adult subjects (mean age 37.7 years; M/F 8/4). Counts were performed, at a constant magnification (×200), by computer-aided analysis and the results expressed as median percentages of positive enterocytes. Results: The results showed a significant increase in enterocyte apoptosis in the elderly (15.3 vs. 2.1% in the adults, p < 0.001) which was positively correlated (r_s = 0.65, p < 0.05) with a significant increase in enterocyte proliferation (37.7 vs. 15.8% in the adults, p < 0.0001). Conclusions: These data suggest that the maintenance of mucosal architecture throughout the process of aging is due to either a hyperproliferative state or an exaggerated apoptosis with a consequent cellular immaturity, which may impair the absorptive function observed in stress conditions.

Puma and p21 represent cooperating checkpoints limiting self-renewal and chromosomal instability of somatic stem cells in response to telomere dysfunction

“…These results could be relevant for human ageing, which is characterized by telomere shortening 26 , an accumulation of DNA damage 27 and elevated rates of apoptosis [28][29][30] . On the basis of these results, apoptosis inhibitors 31 could have beneficial effects on organ maintenance in aged tissues or disease tissues exhibiting telomere shortening and increased rates of apoptosis, for example liver cirrhosis 32 , lung fibrosis 33 and myelodysplastic syndromes 34 .…”

Detection of Alkaline Sphingomyelinase Activity in Human Stool: Proposed Role as a New Diagnostic and Prognostic Marker of Colorectal Cancer

“…At the intestinal level in this pathway, the first step, which leads to ceramide and phosphorylcholine generation, is catalyzed mainly by alkaline sphingomyelinase, an enzyme with a high activity not only in the mucosa but also in the lumen, because it may originate from the sloughing of epithelial cells and from the dissociation of the enzyme from the mucosal surface caused by lumenal factors, primarily the bile salts (31). Alkaline sphingomyelinase, by exerting a major role in dietary sphingomyelin digestion, is responsible for the generation of antiproliferative and/or apoptosis sphingolipid messengers, mainly ceramide, which are able to trigger the rapid turnover and apoptosis in intestinal and colon epithelial cells (13,(32)(33)(34)(35)(36). Markedly reduced mucosal alkaline sphingomyelinase activity has been associated with colorectal carcinoma (23), colorectal adenomas (15), familial adenomatous polyposis (24), and Figure 3.…”

Mitochondrial DNA polymerase editing mutation, PolgD257A, disturbs stem-progenitor cell cycling in the small intestine and restricts excess fat absorption

“…These differentiated epithelial cells reach the tip of villi in ϳ4 days, undergo programmed cell death, and slough off into the intestinal lumen. Aging of the human small intestine is associated with increased proliferation and apoptosis of enterocytes (10). Similarly, cell proliferation in the small intestines of rats increases with age (26,51); however, apoptosis decreases with age (51).…”