Generalized neuromuscular hypoplasia, reduced smooth muscle myosin and altered gut motility in the klotho model of premature aging

D. T. Asuzu, Y. Hayashi, F. Izbeki, L. N. Popko, D. L. Young, M. R. Bardsley, A. Lorincz, M. Kuro-o, D. R. Linden, G. Farrugia, T. Ordog

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background Gastrointestinal symptoms, particularly constipation, increase with aging, but their underlying mechanisms are poorly understood due to lack of experimental models. Previously we established the progeric klotho mouse as a model of aging-associated anorexia and gastric dysmotility. We also detected reduced fecal output in these animals; therefore, the aim of this study was to investigate in vivo function and cellular make-up of the small intestinal and colonic neuromuscular apparatus. Methods Klotho expression was studied by RT-PCR and immunohistochemistry. Motility was assessed by dye transit and bead expulsion. Smooth muscle and neuron-specific gene expression was studied by Western immunoblotting. Interstitial cells of Cajal (ICC) and precursors were analyzed by flow cytometry, confocal microscopy, and three-dimensional reconstruction. HuC/D + myenteric neurons were enumerated by fluorescent microscopy. Key Results Klotho protein was detected in neurons, smooth muscle cells, and some ICC classes. Small intestinal transit was slower but whole-gut transit of klotho mice was accelerated due to faster colonic transit and shorter intestinal lengths, apparent only after weaning. Fecal water content remained normal despite reduced output. Smooth muscle myosin expression was reduced. ICC, ICC precursors, as well as nitrergic and cholinergic neurons maintained their normal proportions in the shorter intestines. Conclusions & Inferences Progeric klotho mice express less contractile proteins and develop generalized intestinal neuromuscular hypoplasia mainly arising from stunted postweaning growth. As reduced fecal output in these mice occurs in the presence of accelerated colonic and whole-gut transit, it likely reflects reduced food intake rather than intestinal dysmotility.

Original languageEnglish (US)
JournalNeurogastroenterology and Motility
Volume23
Issue number7
DOIs
StatePublished - Jul 2011

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Interstitial Cells of Cajal
Smooth Muscle Myosins
Premature Aging
Neurons
Nitrergic Neurons
Growth Disorders
Contractile Proteins
Cholinergic Neurons
Anorexia
Constipation
Weaning
Confocal Microscopy
Smooth Muscle Myocytes
Intestines
Smooth Muscle
Microscopy
Stomach
Flow Cytometry
Theoretical Models
Coloring Agents

Keywords

  • Aging
  • Enteric neurons
  • Gastrointestinal motility
  • Interstitial cells of Cajal
  • Smooth muscle

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

Generalized neuromuscular hypoplasia, reduced smooth muscle myosin and altered gut motility in the klotho model of premature aging. / Asuzu, D. T.; Hayashi, Y.; Izbeki, F.; Popko, L. N.; Young, D. L.; Bardsley, M. R.; Lorincz, A.; Kuro-o, M.; Linden, D. R.; Farrugia, G.; Ordog, T.

In: Neurogastroenterology and Motility, Vol. 23, No. 7, 07.2011.

Research output: Contribution to journalArticle

Asuzu, D. T. ; Hayashi, Y. ; Izbeki, F. ; Popko, L. N. ; Young, D. L. ; Bardsley, M. R. ; Lorincz, A. ; Kuro-o, M. ; Linden, D. R. ; Farrugia, G. ; Ordog, T. / Generalized neuromuscular hypoplasia, reduced smooth muscle myosin and altered gut motility in the klotho model of premature aging. In: Neurogastroenterology and Motility. 2011 ; Vol. 23, No. 7.
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abstract = "Background Gastrointestinal symptoms, particularly constipation, increase with aging, but their underlying mechanisms are poorly understood due to lack of experimental models. Previously we established the progeric klotho mouse as a model of aging-associated anorexia and gastric dysmotility. We also detected reduced fecal output in these animals; therefore, the aim of this study was to investigate in vivo function and cellular make-up of the small intestinal and colonic neuromuscular apparatus. Methods Klotho expression was studied by RT-PCR and immunohistochemistry. Motility was assessed by dye transit and bead expulsion. Smooth muscle and neuron-specific gene expression was studied by Western immunoblotting. Interstitial cells of Cajal (ICC) and precursors were analyzed by flow cytometry, confocal microscopy, and three-dimensional reconstruction. HuC/D + myenteric neurons were enumerated by fluorescent microscopy. Key Results Klotho protein was detected in neurons, smooth muscle cells, and some ICC classes. Small intestinal transit was slower but whole-gut transit of klotho mice was accelerated due to faster colonic transit and shorter intestinal lengths, apparent only after weaning. Fecal water content remained normal despite reduced output. Smooth muscle myosin expression was reduced. ICC, ICC precursors, as well as nitrergic and cholinergic neurons maintained their normal proportions in the shorter intestines. Conclusions & Inferences Progeric klotho mice express less contractile proteins and develop generalized intestinal neuromuscular hypoplasia mainly arising from stunted postweaning growth. As reduced fecal output in these mice occurs in the presence of accelerated colonic and whole-gut transit, it likely reflects reduced food intake rather than intestinal dysmotility.",
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T1 - Generalized neuromuscular hypoplasia, reduced smooth muscle myosin and altered gut motility in the klotho model of premature aging

AU - Asuzu, D. T.

AU - Hayashi, Y.

AU - Izbeki, F.

AU - Popko, L. N.

AU - Young, D. L.

AU - Bardsley, M. R.

AU - Lorincz, A.

AU - Kuro-o, M.

AU - Linden, D. R.

AU - Farrugia, G.

AU - Ordog, T.

PY - 2011/7

Y1 - 2011/7

N2 - Background Gastrointestinal symptoms, particularly constipation, increase with aging, but their underlying mechanisms are poorly understood due to lack of experimental models. Previously we established the progeric klotho mouse as a model of aging-associated anorexia and gastric dysmotility. We also detected reduced fecal output in these animals; therefore, the aim of this study was to investigate in vivo function and cellular make-up of the small intestinal and colonic neuromuscular apparatus. Methods Klotho expression was studied by RT-PCR and immunohistochemistry. Motility was assessed by dye transit and bead expulsion. Smooth muscle and neuron-specific gene expression was studied by Western immunoblotting. Interstitial cells of Cajal (ICC) and precursors were analyzed by flow cytometry, confocal microscopy, and three-dimensional reconstruction. HuC/D + myenteric neurons were enumerated by fluorescent microscopy. Key Results Klotho protein was detected in neurons, smooth muscle cells, and some ICC classes. Small intestinal transit was slower but whole-gut transit of klotho mice was accelerated due to faster colonic transit and shorter intestinal lengths, apparent only after weaning. Fecal water content remained normal despite reduced output. Smooth muscle myosin expression was reduced. ICC, ICC precursors, as well as nitrergic and cholinergic neurons maintained their normal proportions in the shorter intestines. Conclusions & Inferences Progeric klotho mice express less contractile proteins and develop generalized intestinal neuromuscular hypoplasia mainly arising from stunted postweaning growth. As reduced fecal output in these mice occurs in the presence of accelerated colonic and whole-gut transit, it likely reflects reduced food intake rather than intestinal dysmotility.

AB - Background Gastrointestinal symptoms, particularly constipation, increase with aging, but their underlying mechanisms are poorly understood due to lack of experimental models. Previously we established the progeric klotho mouse as a model of aging-associated anorexia and gastric dysmotility. We also detected reduced fecal output in these animals; therefore, the aim of this study was to investigate in vivo function and cellular make-up of the small intestinal and colonic neuromuscular apparatus. Methods Klotho expression was studied by RT-PCR and immunohistochemistry. Motility was assessed by dye transit and bead expulsion. Smooth muscle and neuron-specific gene expression was studied by Western immunoblotting. Interstitial cells of Cajal (ICC) and precursors were analyzed by flow cytometry, confocal microscopy, and three-dimensional reconstruction. HuC/D + myenteric neurons were enumerated by fluorescent microscopy. Key Results Klotho protein was detected in neurons, smooth muscle cells, and some ICC classes. Small intestinal transit was slower but whole-gut transit of klotho mice was accelerated due to faster colonic transit and shorter intestinal lengths, apparent only after weaning. Fecal water content remained normal despite reduced output. Smooth muscle myosin expression was reduced. ICC, ICC precursors, as well as nitrergic and cholinergic neurons maintained their normal proportions in the shorter intestines. Conclusions & Inferences Progeric klotho mice express less contractile proteins and develop generalized intestinal neuromuscular hypoplasia mainly arising from stunted postweaning growth. As reduced fecal output in these mice occurs in the presence of accelerated colonic and whole-gut transit, it likely reflects reduced food intake rather than intestinal dysmotility.

KW - Aging

KW - Enteric neurons

KW - Gastrointestinal motility

KW - Interstitial cells of Cajal

KW - Smooth muscle

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