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Updated: May 1, 2026

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
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Aging-associated oxidative stress leads to decrease in IAS tone via RhoA/ROCK downregulation.

Jagmohan Singh1, Sumit Kumar1, Chadalavada Vijay Krishna1

  • 1Division of Gastroenterology and Hepatology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.

American Journal of Physiology. Gastrointestinal and Liver Physiology
|April 19, 2014
PubMed
Summary
This summary is machine-generated.

Aging decreases internal anal sphincter (IAS) tone, potentially causing incontinence. Oxidative stress exacerbates this decline by disrupting the RhoA/ROCK pathway, a finding reversible with antioxidants.

Keywords:
RhoA/ROCKaginginternal anal sphincteroxidative stressrectoanal incontinence

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Area of Science:

  • Physiology
  • Gastroenterology
  • Aging Research

Background:

  • Internal anal sphincter (IAS) tone is crucial for preventing rectoanal incontinence (RI).
  • Aging can compromise IAS tone, contributing to RI in some individuals.
  • The role of oxidative stress in age-associated IAS tone decline (AADI) requires further investigation.

Purpose of the Study:

  • To investigate the influence of oxidative stress on AADI.
  • To elucidate the involvement of the RhoA/ROCK signal transduction cascade in this process.
  • To determine the effects of superoxide anions and their scavengers on IAS tone.

Main Methods:

  • Utilized adult and aging rat models.
  • Administered the oxidative stress inducer LY83583 and the scavenger SOD to IAS smooth muscle strips and cells.
  • Assessed RhoA/ROCK expression and signal transduction.
  • Measured IAS tone changes in response to agonists and inhibitors.

Main Results:

  • AADI correlated with reduced RhoA/ROCK expression at both transcriptional and translational levels.
  • Oxidative stress (LY83583) decreased IAS tone and smooth muscle cell relaxation, linked to diminished RhoA/ROCK signaling, which SOD reversed.
  • LY83583 inhibited U46619-induced IAS contraction, an effect also reversed by SOD.

Conclusions:

  • Increased oxidative stress significantly contributes to AADI in aging individuals.
  • Disruption of the RhoA/ROCK pathway by oxidative stress is a key mechanism underlying AADI.
  • These findings suggest oxidative stress management may be a therapeutic target for RI in the elderly.