Cellular changes in the enteric nervous system during ageing

• Published in: Developmental biology 2013-10, Vol.382 (1), p.344-355
• Main Author: Saffrey, M. Jill
• Format: Article
• Language: English
• Subjects: Aging; Aging - pathology; animal models; Animals; Caloric restriction; cell death; Cell senescence; elderly; Enteric nervous system; Enteric Nervous System - growth & development; Enteric Nervous System - pathology; ganglia; Gastrointestinal Tract - innervation; Gastrointestinal Tract - pathology; Gut–brain axis; Humans; immune system; Inflammation; intestinal mucosa; low calorie diet; Microbiota; microorganisms; Nerve Degeneration - pathology; Neurodegeneration; neurodegenerative diseases; Neurogenesis; neurons; Neurons - pathology; Neurotrophic factors; Oxidative stress; phenotype; reactive oxygen species
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2013.03.015

The intrinsic neurons of the gut, enteric neurons, have an essential role in gastrointestinal functions. The enteric nervous system is plastic and continues to undergo changes throughout life, as the gut grows and responds to dietary and other environmental changes. Detailed analysis of changes in the ENS during ageing suggests that enteric neurons are more vulnerable to age-related degeneration and cell death than neurons in other parts of the nervous system, although there is considerable variation in the extent and time course of age-related enteric neuronal loss reported in different studies. Specific neuronal subpopulations, particularly cholinergic myenteric neurons, may be more vulnerable than others to age-associated loss or damage. Enteric degeneration and other age-related neuronal changes may contribute to gastrointestinal dysfunction that is common in the elderly population. Evidence suggests that caloric restriction protects against age-associated loss of enteric neurons, but recent advances in the understanding of the effects of the microbiota and the complex interactions between enteric ganglion cells, mucosal immune system and intestinal epithelium indicate that other factors may well influence ageing of enteric neurons. Much remains to be understood about the mechanisms of neuronal loss and damage in the gut, although there is evidence that reactive oxygen species, neurotrophic factor dysregulation and/or activation of a senescence associated phenotype may be involved. To date, there is no evidence for ongoing neurogenesis that might replace dying neurons in the ageing gut, although small local sites of neurogenesis would be difficult to detect. Finally, despite the considerable evidence for enteric neurodegeneration during ageing, and evidence for some physiological changes in animal models, the ageing gut appears to maintain its function remarkably well in animals that exhibit major neuronal loss, indicating that the ENS has considerable functional reserve. •The adult ENS is plastic, but no evidence shows neurogenesis in undamaged gut.•Data vary, but suggest degeneration and loss of enteric neurons during ageing.•Caloric restriction protects against neuronal losses in the ageing ENS.•The causes and mechanisms of enteric neurodegeneration are now being investigated.•The role of cellular ageing in changes of gut functions remain to be determined.