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Induction and Validation of Cellular Senescence in Primary Human Cells
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MHY2233 Attenuates Replicative Cellular Senescence in Human Endothelial Progenitor Cells via SIRT1 Signaling

Shreekrishna Lamichane1,2, Sang Hong Baek3, Yeon-Ju Kim4

  • 1Convergence Stem Cell Research Center, Pusan National University, Yangsan, Republic of Korea.

Oxidative Medicine and Cellular Longevity
|June 22, 2019
PubMed

Insights

MHY2233, a SIRT1 activator, combats cellular senescence in endothelial progenitor cells (EPCs). This antiaging compound enhances EPC function, offering potential for treating age-associated cardiovascular diseases (CVDs).

Area of Science:

  • Cardiovascular Research
  • Stem Cell Biology
  • Aging and Gerontology

Background:

  • Cardiovascular diseases (CVDs) are a leading global cause of mortality.
  • Pharmacotherapies for CVDs often result in side effects and incomplete recovery.
  • Stem cell therapy, particularly using endothelial progenitor cells (EPCs), shows promise for CVD treatment, but cellular senescence impairs EPC function.

Purpose of the Study:

  • To investigate the effect of MHY2233, a novel SIRT1 activator, on cellular senescence in EPCs.
  • To evaluate MHY2233's potential as a therapeutic agent for age-associated CVDs.

Main Methods:

  • Assessed MHY2233's impact on SIRT1 expression and deacetylase activity.
  • Measured changes in senescence biomarkers (p53, p16, p21) and SA-β-gal positive cells.
  • Evaluated MHY2233's effects on senescence-associated secretory phenotypes (SASPs) and oxidative stress markers (ROS) in EPCs.
  • Assessed the functional recovery of senescent EPCs, including angiogenesis, proliferation, and migration.

Main Results:

  • MHY2233 increased SIRT1 expression and activity, reducing senescence biomarkers and SA-β-gal positive cells.
  • MHY2233 decreased SASP factors (IL-6, IL-8, IL-1α, IL-1β) and cellular ROS levels.
  • Treatment with MHY2233 enhanced angiogenesis, proliferation, and migration of senescent EPCs, improving cell survival and function.

Conclusions:

  • MHY2233 effectively reduces replicative and oxidative stress-induced senescence in EPCs.
  • The compound MHY2233 demonstrates potential as a therapeutic agent for age-associated cardiovascular diseases by rejuvenating EPC function.

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