Related Experiment Video

Updated: Jul 4, 2026

Induction and Validation of Cellular Senescence in Primary Human Cells
08:18

Induction and Validation of Cellular Senescence in Primary Human Cells

Published on: June 20, 2018

PPAR{gamma} accelerates cellular senescence by inducing p16INK4{alpha} expression in human diploid fibroblasts

Qini Gan1, Jing Huang, Rui Zhou

  • 1Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100083, People's Republic of China.

Journal of Cell Science
|June 12, 2008
PubMed

Insights

Peroxisome proliferator-activated receptor gamma (PPARgamma) promotes cellular senescence by increasing p16(INK4alpha) expression, accelerating cell-cycle arrest and aging in human fibroblasts.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to inhibit cell growth by inducing cell-cycle arrest.
  • PPARgamma activation upregulates p16(INK4alpha) (CDKN2A), a key cell-cycle inhibitor that can trigger senescence.
  • The specific role of PPARgamma in the process of cellular senescence remained unclear.

Purpose of the Study:

  • To investigate the role of PPARgamma in cellular senescence.
  • To elucidate the molecular mechanism by which PPARgamma influences senescence.
  • To determine if PPARgamma activation promotes or inhibits cellular senescence.

Main Methods:

  • Human fibroblasts were treated with a selective PPARgamma agonist.
  • Senescence was assessed using senescence-associated beta-galactosidase staining and cell-cycle analysis (G1 arrest).
  • Western blotting was employed to measure p16(INK4alpha) expression, and PPARgamma binding to the p16 promoter was analyzed.

Main Results:

  • PPARgamma activation accelerated cellular senescence, evidenced by increased SA-beta-galactosidase staining and G1 arrest.
  • Western blotting confirmed that PPARgamma activation upregulates p16(INK4alpha) expression.
  • PPARgamma was shown to bind to the p16 promoter, inducing its transcription, with higher p16(INK4alpha) expression observed in senescent cells.

Conclusions:

  • PPARgamma plays a role in promoting cellular senescence by inducing p16(INK4alpha) expression.
  • The study provides a molecular mechanism for PPARgamma-mediated regulation of cellular senescence.
  • Decreased PPARgamma phosphorylation with increased cell passage suggests a role in age-related senescence.

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...