Age-associated remodeling of the intestinal epithelial barrier

J Gerontol A Biol Sci Med Sci. 2013 Sep;68(9):1045-56. doi: 10.1093/gerona/glt106. Epub 2013 Jul 20.

Abstract

Disorders of the gastrointestinal tract are common in the elderly people; however, the precise trait(s) of aging that contribute to the vulnerability of the gastrointestinal tract are poorly understood. Recent evidence suggests that patients with gastrointestinal disorders have increased intestinal permeability. Here, we address the hypothesis that disruption of the intestinal barrier is associated with aging. Our results demonstrated that permeability was significantly higher in colonic biopsies collected from old baboons compared with young baboons. Additionally, colonic tissue from the older animals had decreased zonula occluden-1, occludin, and junctional adhesion molecule-A tight junction protein expression and increased claudin-2 expression. Upregulation of miR-29a and inflammatory cytokines IFN-γ, IL-6, and IL-1β was also found in colonic biopsies from old baboons relative to young baboons. These results show for the first time that a pivotal contributing factor to geriatric vulnerability to gastrointestinal dysfunction may be increased colonic permeability via age-associated remodeling of intestinal epithelial tight junction proteins.

Keywords: Aging; Cytokines; MicroRNA; Permeability; Tight junctions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / genetics
  • Aging / pathology
  • Aging / physiology*
  • Animals
  • Colon / pathology
  • Colon / physiology
  • Cytokines / biosynthesis
  • Gastrointestinal Diseases / etiology
  • Gastrointestinal Diseases / pathology
  • Gastrointestinal Diseases / physiopathology
  • Glutamate-Ammonia Ligase / metabolism
  • Humans
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Papio anubis / anatomy & histology
  • Papio anubis / genetics
  • Papio anubis / physiology*
  • Permeability
  • Peroxidase / metabolism
  • Risk Factors
  • Tight Junction Proteins / metabolism

Substances

  • Cytokines
  • MicroRNAs
  • Tight Junction Proteins
  • Peroxidase
  • Glutamate-Ammonia Ligase