Reduced intestinal motility, mucosal barrier function, and inflammation in aged monkeys

Abstract

Objective: We aimed to examine the general health and intestinal physiology of young and old non-human primates with comparable life histories and dietary environments. Design: Vervet monkeys (Chlorcebus aethiops sabaeus) in stable and comparable social and nutritional environments were selected for evaluation. Health phenotype, circulating cytokines and biomarkers of microbial translocation (MT) were measured (n=26–44). Subsets of monkeys additionally had their intestinal motility, intestinal permeability, and fecal microbiomes characterized. These outcomes document age-related intestinal changes present in the absence of nutritional stressors, which are all known to affect gastrointestinal motility, microbiome, and MT. Results: We found that old monkeys have greater systemic inflammation and poor intestinal barrier function as compared to young monkeys. Old monkeys have dramatically reduced intestinal motility, and all changes in motility and MT are present without large differences in fecal microbiomes. Conclusion: We conclude that deteriorating intestinal function is a feature of normal aging and could represent the source of inflammatory burden yet to be explained by disease or diet in normal aging human primate populations. Intestinal changes were seen independent of dietary influences and aging within a consistent environment appears to avoid major microbiome shifts. Our data suggests interventions to promote intestinal motility and mucosal barrier function have the potential to support better health with aging.

Epithelial Barrier Function in Gut-Bone Signaling

“…The older baboons displayed a significant decrease in ZO-1, occludin, and JAM-A proteins, and an increase in claudin-2 expression, all of which correlated with increased permeability in the old aged group [66]. Another study in monkeys found that old monkeys have an increase in FITC dextran flux compared to young monkeys [67]. …”

“…Several studies have reported a dysregulation in the intestinal immune homeostasis in different models of aging. Specifically, it has been shown that the function of the gut-associated immune system is impaired in elderly humans [67, 69, 73, 74]. …”

“…This increase in inflammation was attributed to an increase in serum CRP [67]. In a similar study using baboons, it was found that aged baboons have a significant increase in IFN-γ, IL-6, and IL-β in colonic biopsies.…”

“…Specifically, the strongest link between gut permeability and bone loss comes from colitis studies where barrier disruption in adult animal models leads to bone loss, even without weight loss [84][85][62]. Thus, as animals and humans age, intestinal permeability increases [64][65][66][67][62][69] and could contributes to age-related bone loss. In addition, increased permeability likely promotes the low-grade chronic inflammation, termed “inflammageing” [72][67][75], and many studies link low grade inflammation with bone loss [84][85][62].…”

“…Thus, as animals and humans age, intestinal permeability increases [64][65][66][67][62][69] and could contributes to age-related bone loss. In addition, increased permeability likely promotes the low-grade chronic inflammation, termed “inflammageing” [72][67][75], and many studies link low grade inflammation with bone loss [84][85][62]. In the future, studies are need to test if a direct link exists between barrier function and bone health in the elderly, since this could be a promising target for new therapeutics.…”