Research Paper Volume 10, Issue 12 pp 3851—3865

Aging-dependent decrease in the numbers of enteric neurons, interstitial cells of Cajal and expression of connexin43 in various regions of gastrointestinal tract

Tingyi Sun 1, 2, 3, , Dandan Li 1, , Shilong Hu 1, , Li Huang 1, , Haimei Sun 1, 2, 3, , Shu Yang 1, 2, 3, , Bo Wu 1, 2, 3, , Fengqing Ji 1, 2, 3, , Deshan Zhou 1, 2, 3, ,

  • 1 Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China
  • 2 Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, 100069, China
  • 3 Cancer Institute of Capital Medical University, Beijing, 100069, China

received: July 28, 2018 ; accepted: November 18, 2018 ; published: December 11, 2018 ;
How to Cite

Copyright: Sun et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Aging is a significant risk factor for gastrointestinal dysmotility, but aging-associated differences between different organs and the exact time to start degenerating have remained obscure. Here we evaluated alterations of interstitial cells of Cajal, enteric neurons and connexin43 expression in the stomach, jejunum and colon in 2-, 12-, 16-, 20- and 24-month-old mice, as well as in aged human colon. Interstitial cells of Cajal, cholinergic and nitrergic neurons within the whole digestive tract were reduced over time, but their loss first appeared in stomach, then in intestine, helping to understand that gastric function was first impaired during aging. The decrease of connexin43 expression occurred before interstitial cells of Cajal and neurons loss, suggesting that connexin43 might be the major target influenced during senescence. Furthermore, changes in expressions of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin-1β, interleukin-6) and apoptosis-related proteins (B-cell lymphoma-2, caspase-3) which indicated “inflammaging”, might contribute to the loss of enteric neurons and interstitial cells of Cajal in aged gastrointestinal tract. Our results provide possible therapeutic time window for beneficial intervention for geriatric patients with gastrointestinal motility disorders.


GI: gastrointestinal; ICCs: interstitial cells of Cajal; SMCs: smooth muscle cells; ENS: enteric nervous system; MP: myenteric plexus; Cx43: connexin43; mo: months; NADPH-d: NADPH-diaphorase; ChAT: choline acetyltransferase; NOS: nitric oxide synthase; nNOS: neuronal nitric oxide synthase; PGP9.5: protein gene product 9.5; HuC/D: human neuronal protein HuC/HuD; TNF-α: tumour necrosis factor-α; IL: interleukin; Bcl-2: B-cell lymphoma-2; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.